Search

Herpes zoster is caused by the reactivation of latent varicella-zoster virus from dorsal root ganglia. Although infrequent, simultaneous damage to the anterior horn cells or anterior nerve roots at the same level may result in motor neuropathy. When motor involvement is localized in the abdominal wall, a pseudohernia may be the clinical presentation. We report a case of abdominal wall post-herpetic pseudohernia, with clinical, ultrasound and MRI correlation. MRI demonstrated increased T2/STIR signal intensity in the abdominal wall muscles, suggesting acute denervation. To our knowledge, this is the first case report of postherpetic pseudohernia with acute denervation demonstrated on MRI., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Despite the high prevalence of chronic multisite pain, there is little consensus on methods to characterize it. Commonly used assessments report only one dimension of pain, that is, intensity, thus ignoring the spatial aspect of pain. We developed a novel pain quantification index, the Integrated Pain Quantification Index (IPQI), on a scale of 0 to 1 that integrates multiple distinct pain measures into a single value, thus representing multidimensional pain information with a single value., Design: Single-visit, noninterventional, epidemiological study., Setting: Fourteen outpatient multidisciplinary pain management programs., Patients: Patients with chronic pain of the trunk and/or limbs for at least six months with average overall pain intensity of at least 5 on the numeric rating scale., Methods: Development of IPQI was performed in a large population (N = 810) of chronic pain patients from the Multiple Areas of Pain (MAP) study., Results: Prevalence of two or more noncontiguous painful areas was at 88.3% (95% confidence interval [CI] = 0.86-0.90), with a mean of 6.3 areas (SD = 5.57 areas). Prevalence of more than 10% body area in pain was at 52.8% (95% CI = 0.49-0.56), with a mean at 16.1% (17.16%). On average, IPQI values were near the middle of the scale, with mean and median IPQI at 0.52 (SD = 0.13) and 0.55, respectively. The IPQI was generalizable and clinically relevant across all domains recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials., Conclusions: IPQI provided a single pain score for representing complex, multidimensional pain information on one scale and has implications for comparing pain populations across longitudinal clinical trials., (© 2018 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Sheep have been traditionally considered as less susceptible to Mycobacterium bovis (Mbovis) infection than other domestic ruminants such as cattle and goats. However, there is increasing evidence for the role of this species as a domestic Mbovis reservoir, mostly when sheep share grazing fields with infected cattle and goats. Nevertheless, there is a lack of information about the pathogenesis and the immune response of Mbovis infection in sheep. The goals of this study were to characterize the granuloma stages produced by the natural infection of Mbovis in sheep, to compare them with other species and to identify possible differences in the sheep immune response. Samples from bronchial lymph nodes from twelve Mbovis-naturally infected sheep were used. Four immunohistochemical protocols for the specific detection of T-lymphocytes, B-lymphocytes, plasma cells and macrophages were performed to study the local immune reaction within the granulomas., Results: Differences were observed in the predominant cell type present in each type of granuloma, as well as differences and similarities with the development of tuberculous granulomas in other species. Very low numbers of T-lymphocytes were observed in all granuloma types indicating that specific cellular immune response mediated by T-cells might not be of much importance in sheep in the early stages of infection, when macrophages are the predominant cell type within lesions. Plasma cells and mainly B lymphocytes increased considerably as the granuloma developed being attracted to the lesions in a shift towards a Th2 response against the increasing amounts of mycobacteria. Therefore, we have proposed that the granulomas could be defined as initial, developed and terminal., Conclusions: Results showed that the study of the lymphoid tissue granulomata reinforces the view that the three different types of granuloma represent stages of lesion progression and suggest an explanation to the higher resistance of sheep based on a higher effective innate immune response to control tuberculosis infection.

Study Design: Literature review., Objective: A review of the literature that presents a perspective on mechanisms of actions behind spinal cord stimulation (SCS) therapy for chronic pain., Summary of Background Data: SCS is an effective therapeutic alternative for the treatment of intractable chronic pain. Its application has been mostly based on the gate control theory of pain. Computational models have been fundamental on the understanding of clinical observations and the design of therapies that provide optimal neuromodulation. Research has provided insight into the involvement of specific neurotransmitters that support segmental and supraspinal mechanisms of action., Methods: A literature review was performed with emphasis on mechanisms of action for SCS including the effects of electrical fields on spinal cord structures based on computational models and preclinical and clinical explorations., Results: This review provides background on the development of SCS, which has been driven around a paresthesia-based paradigm as a result of the gate control theory. A review of computational models emphasizes their importance on our current understanding of the mechanism of action and clinical optimization of therapy. Electrophysiology and molecular biology have provided a closer, yet narrow, view of the effect of SCS on neurotransmitters and their receptors, which have led to the formulation of segmental and supraspinal mechanisms. Literature supporting the involvement of glial cells in chronic pain and their characteristic response to electrical fields should motivate further investigation of mechanisms involving neuroglia. Finally, a review of recent results paresthesia-free strategies should encourage research on mechanisms of action., Conclusion: The mechanisms of SCS have been extensively studied and several consistent phenomena have emerged. The activation of A-beta fibers to induce paresthesia also involve neurotransmitter release via segmental and supraspinal pathways. Despite advancements, much remains to be understood, particularly as new stimulation strategies are developed., Level of Evidence: N /A.

Background: Spinal cord stimulation (SCS) has been successfully used to treat chronic intractable pain for over 40 years. Successful clinical application of SCS is presumed to be generally dependent on maximizing paresthesia-pain overlap; critical to achieving this is positioning of the stimulation field at the physiologic midline. Recently, the necessity of paresthesia for achieving effective relief in SCS has been challenged by the introduction of 10 kHz paresthesia-free stimulation. In a large, prospective, randomized controlled pivotal trial, HF10 therapy was demonstrated to be statistically and clinically superior to paresthesia-based SCS in the treatment of severe chronic low back and leg pain. HF10 therapy, unlike traditional paresthesia-based SCS, requires no paresthesia to be experienced by the patient, nor does it require paresthesia mapping at any point during lead implant or post-operative programming., Objectives: To determine if pain relief was related to technical factors of paresthesia, we measured and analyzed the paresthesia responses of patients successfully using HF10 therapy., Study Design: Prospective, multicenter, non-randomized, non-controlled interventional study., Setting: Outpatient pain clinic at 10 centers across the US and Italy., Methods: Patients with both back and leg pain already implanted with an HF10 therapy device for up to 24 months were included in this multicenter study. Patients provided pain scores prior to and after using HF10 therapy. Each patient's most efficacious HF10 therapy stimulation program was temporarily modified to a low frequency (LF; 60 Hz), wide pulse width (~470 mus), paresthesia-generating program. On a human body diagram, patients drew the locations of their chronic intractable pain and, with the modified program activated, all regions where they experienced LF paresthesia. Paresthesia and pain drawings were then analyzed to estimate the correlation of pain relief outcomes to overlap of pain by paresthesia, and the mediolateral distribution of paresthesia (as a surrogate of physiologic midline lead positioning)., Results: A total of 61 patients participated across 11 centers. Twenty-eight men and 33 women with a mean age of 56 ± 12 years of age participated in the study. The average duration of implantable pulse generator (IPG) implant was 19 ± 9 months. The average predominant pain score, as measured on a 0 - 10 visual analog scale (VAS), prior to HF10 therapy was 7.8 ± 1.3 and at time of testing was 2.5 ± 2.1, yielding an average pain relief of 70 ± 24%. For all patients, the mean paresthesia coverage of pain was 21 ± 28%, with 43% of patients having zero paresthesia coverage of pain. Analysis revealed no correlation between percentage of LF paresthesia overlap of predominant pain and HF10 therapy efficacy (P = 0.56). Exact mediolateral positioning of the stimulation electrodes was not found to be a statistically significant predictor of pain relief outcomes., Limitations: Non-randomized/non-controlled study design; short-term evaluation; certain technical factors not investigated., Conclusion: Both paresthesia concordance with pain and precise midline positioning of the stimulation contacts appear to be inconsequential technical factors for successful HF10 therapy application. These results suggest that HF10 therapy is not only paresthesia-free, but may be paresthesia-independent.

Objective: This report conveys 12-month outcomes of subjects treated with intradiscal biacuplasty (IDB) and conservative medical management (CMM) for chronic low back pain of discogenic origin, and results for subjects who elected to receive IDB + CMM 6 months after CMM-alone., Methods: Sixty-three subjects were originally randomized to the IDB + CMM group (N = 29) or CMM-alone (N = 34). Six months following continuous CMM-alone treatment, participants in this study group were permitted to "cross-over" to IDB + CMM (N = 25), and followed for an additional 6 months. The original IDB + CMM study subjects were followed for a total of 12 months (N = 22)., Results: Pain reduction at 12 months was statistically significant and clinically meaningful in the original IDB + CMM group compared to baseline. Functional and disability outcomes were also improved statistically and clinically. Fifty-five percent of the IDB + CMM patients responded to treatment with a mean VAS reduction of 2.2 points at 12 months. Furthermore, 50% and 64% of subjects reported clinically significant improvements in SF36-PF and in ODI, respectively. There was a 1.7-point reduction (improvement) on a 7-point PGIC scale, and a 0.13-point increase (improvement) in the EQ-5D Health Index. Fifty-percent of cross-over subjects responded to IDB + CMM intervention. Mean outcome scores for cross-over subjects were similar to those of the originally-treated subjects, and functional and disability endpoints were improved statistically and clinically compared to respective baseline values., Conclusions: The study demonstrated long-term clinical effectiveness of IDB + CMM for treating chronic lumbar discogenic pain. Furthermore, the cross-over study subjects experienced similar improvements in pain, function, disability, and satisfaction., (© 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Background and Objectives: Spinal cord stimulation (SCS) has been shown to influence pain-related genes in the spinal cord directly under the stimulating electrodes. There is limited information regarding changes occurring at the dorsal root ganglion (DRG). This study evaluates gene expression in the DRG in response to SCS therapy., Methods: Rats were randomized into experimental or control groups (n = 6 per group). Experimental animals underwent spared-nerve injury, implantation of lead, and continuous SCS (72 hours). Behavioral assessment for mechanical hyperalgesia was conducted to compare responses after injury and treatment. Ipsilateral DRG tissue was collected, and gene expression quantified for interleukin 1b (IL-1b), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), GABA B receptor 1 (GABAbr1), substance P (subP), Integrin alpha M (ITGAM), sodium/potassium ATP-ase (Na/K ATPase), fos proto-oncogene (cFOS), serotonin receptor 3A (5HT3r), galanin (Gal), vasoactive intestinal peptide (VIP), neuropeptide Y (NpY), glial fibrillary acidic protein (GFAP), and brain derived neurotropic factor (BDNF) via quantitative polymerase chain reaction. Statistical significance was established using analysis of variance (ANOVA), independent t tests, and Pearson correlation tests., Results: Expression of IL-1b and IL-6 was reversed following SCS therapy relative to the increase caused by the injury model. Both GABAbr1 and Na/K ATPase were significantly up-regulated upon implantation of the lead, and SCS therapy reversed their expression to within control levels. Pearson correlation analyses reveal that GABAbr1 and Na/K ATPase expression was dependent on the stimulating current intensity., Conclusions: Spinal cord stimulation modulates expression of key pain-related genes in the DRG. Specifically, SCS led to reversal of IL-1b and IL-6 expression induced by injury. Interleukin 6 expression was still significantly larger than in sham animals, which may correlate to residual sensitivity following continuous SCS treatment. In addition, expression of GABAbr1 and Na/K ATPase was down-regulated to within control levels following SCS and correlates with applied current.

Background: Opioid use, abuse, and adverse consequences, including death, have escalated at an alarming rate since the 1990s. In an attempt to control opioid abuse, numerous regulations and guidelines for responsible opioid prescribing have been developed by various organizations. However, the US opioid epidemic is continuing and drug dose deaths tripled during 1999 to 2015. Recent data show a continuing increase in deaths due to natural and semisynthetic opioids, a decline in methadone deaths, and an explosive increase in the rates of deaths involving other opioids, specifically heroin and illicit synthetic fentanyl. Contrary to scientific evidence of efficacy and negative recommendations, a significant proportion of physicians and patients (92%) believe that opioids reduce pain and a smaller proportion (57%) report better quality of life. In preparation of the current guidelines, we have focused on the means to reduce the abuse and diversion of opioids without jeopardizing access for those patients suffering from non-cancer pain who have an appropriate medical indication for opioid use., Objectives: To provide guidance for the prescription of opioids for the management of chronic non-cancer pain, to develop a consistent philosophy among the many diverse groups with an interest in opioid use as to how appropriately prescribe opioids, to improve the treatment of chronic non-cancer pain and to reduce the likelihood of drug abuse and diversion. These guidelines are intended to provide a systematic and standardized approach to this complex and difficult arena of practice, while recognizing that every clinical situation is unique., Methods: The methodology utilized included the development of objectives and key questions. The methodology also utilized trustworthy standards, appropriate disclosures of conflicts of interest, as well as a panel of experts from various specialties and groups. The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed, with a best evidence synthesis of the available literature, and utilized grading for recommendation as described by the Agency for Healthcare Research and Quality (AHRQ).Summary of Recommendations:i. Initial Steps of Opioid Therapy 1. Comprehensive assessment and documentation. (Evidence: Level I; Strength of Recommendation: Strong) 2. Screening for opioid abuse to identify opioid abusers. (Evidence: Level II-III; Strength of Recommendation: Moderate) 3. Utilization of prescription drug monitoring programs (PDMPs). (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 4. Utilization of urine drug testing (UDT). (Evidence: Level II; Strength of Recommendation: Moderate) 5. Establish appropriate physical diagnosis and psychological diagnosis if available. (Evidence: Level I; Strength of Recommendation: Strong) 6. Consider appropriate imaging, physical diagnosis, and psychological status to collaborate with subjective complaints. (Evidence: Level III; Strength of Recommendation: Moderate) 7. Establish medical necessity based on average moderate to severe (≥ 4 on a scale of 0 - 10) pain and/or disability. (Evidence: Level II; Strength of Recommendation: Moderate) 8. Stratify patients based on risk. (Evidence: Level I-II; Strength of Recommendation: Moderate) 9. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. (Evidence: Level I-II; Strength of Recommendation: Moderate) 10. Obtain a robust opioid agreement, which is followed by all parties. (Evidence: Level III; Strength of Recommendation: Moderate)ii. Assessment of Effectiveness of Long-Term Opioid Therapy 11. Initiate opioid therapy with low dose, short-acting drugs, with appropriate monitoring. (Evidence: Level II; Strength of Recommendation: Moderate) 12. Consider up to 40 morphine milligram equivalent (MME) as low dose, 41 to 90 MME as a moderate dose, and greater than 91 MME as high dose. (Evidence: Level II; Strength of Recommendation: Moderate) 13. Avoid long-acting opioids for the initiation of opioid therapy. (Evidence: Level I; Strength of Recommendation: Strong) 14. Recommend methadone only for use after failure of other opioid therapy and only by clinicians with specific training in its risks and uses, within FDA recommended doses. (Evidence: Level I; Strength of Recommendation: Strong) 15. Understand and educate the patients of the effectiveness and adverse consequences. (Evidence: Level I; Strength of Recommendation: Strong) 16. Similar effectiveness for long-acting and short-acting opioids with increased adverse consequences of long-acting opioids. (Evidence: Level I-II; Strength of recommendation: Moderate to strong) 17. Periodically assess pain relief and/or functional status improvement of ≥ 30% without adverse consequences. (Evidence: Level II; Strength of recommendation: Moderate) 18. Recommend long-acting or high dose opioids only in specific circumstances with severe intractable pain. (Evidence: Level I; Strength of Recommendation: Strong)iii. Monitoring for Adherence and Side Effects 19. Monitor for adherence, abuse, and noncompliance by UDT and PDMPs. (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 20. Monitor patients on methadone with an electrocardiogram periodically. (Evidence: Level I; Strength of Recommendation: Strong). 21. Monitor for side effects including constipation and manage them appropriately, including discontinuation of opioids when indicated. (Evidence: Level I; Strength of Recommendation: Strong)iv. Final Phase 22. May continue with monitoring with continued medical necessity, with appropriate outcomes. (Evidence: Level I-II; Strength of Recommendation: Moderate) 23. Discontinue opioid therapy for lack of response, adverse consequences, and abuse with rehabilitation. (Evidence: Level III; Strength of Recommendation: Moderate) CONCLUSIONS: These guidelines were developed based on comprehensive review of the literature, consensus among the panelists, in consonance with patient preferences, shared decision-making, and practice patterns with limited evidence, based on randomized controlled trials (RCTs) to improve pain and function in chronic non-cancer pain on a long-term basis. Consequently, chronic opioid therapy should be provided only to patients with proven medical necessity and stability with improvement in pain and function, independently or in conjunction with other modalities of treatments in low doses with appropriate adherence monitoring and understanding of adverse events.Key words: Chronic pain, persistent pain, non-cancer pain, controlled substances, substance abuse, prescription drug abuse, dependency, opioids, prescription monitoring, drug testing, adherence monitoring, diversionDisclaimer: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

Background and Objectives: Osteoarthrosis is a main cause of knee pain in the elderly. Pain associated with this condition is often refractory to conservative treatment. Total knee replacement may be the best option for severe pathologies; however, the occurrence of a chronic pain state after knee replacement has been well documented in the literature. The previous descriptions of the genicular nerves have been considered somewhat inaccurate. This innervation is complex and exhibits significant interindividual variability. A precise description of these nerves will increase our knowledge on different patterns and targets, to guide treatment and improve outcomes. The objective of this study was to determine sensory innervation patterns of the knee joint and correlate them with dynamic visualization via ultrasound imaging., Methods: Systematic cadaveric dissections were performed to determine different patterns of sensory innervation of the knee followed by ultrasonographic correlation. A short-axis ultrasound view of the nerves was used to inject India ink at several points along their course to facilitate the anatomic dissection and confirm their location among adjacent structures., Results: The visualized structures were the following: infrapatellar branch of the saphenous nerve, the branches to vastus medialis, intermedius, and lateralis muscles; obturator nerve; and lateral retinacular and recurrent peroneal nerves., Conclusions: We conclude that reproducible correlations showing the sensory innervations for the knee are linked to muscular structures. However, high variability among individuals makes it difficult to predict their paths. Our systematic approach, using direct visualization via ultrasound, allows a more accurate placement of the needle for therapeutic purposes.

Background and Objectives: Previously, we found that application of pulsed radiofrequency to a peripheral nerve injury induces changes in key genes regulating nociception concurrent with alleviation of paw sensitivity in an animal model. In the current study, we evaluated such genes after applying spinal cord stimulation (SCS) therapy., Methods: Male Sprague-Dawley rats (n = 6 per group) were randomized into test and control groups. The spared nerve injury model was used to simulate a neuropathic pain state. A 4-contact microelectrode was implanted at the L1 vertebral level and SCS was applied continuously for 72 hours. Mechanical hyperalgesia was tested. Spinal cord tissues were collected and analyzed using real-time polymerase chain reaction to quantify levels of IL1β, GABAbr1, subP, Na/K ATPase, cFos, 5HT3ra, TNFα, Gal, VIP, NpY, IL6, GFAP, ITGAM, and BDNF., Results: Paw withdrawal thresholds significantly decreased in spared nerve injury animals and stimulation attenuated sensitivity within 24 hours (P = 0.049), remaining significant through 72 hours (P = 0.003). Nerve injury caused up-regulation of TNFα, GFAP, ITGAM, and cFOS as well as down-regulation of Na/K ATPase. Spinal cord stimulation therapy modulated the expression of 5HT3ra, cFOS, and GABAbr1. Strong inverse relationships in gene expression relative to the amount of applied current were observed for GABAbr1 (R = -0.65) and Na/K ATPase (R = -0.58), and a positive linear correlations between 5HT3r (R = 0.80) and VIP (R = 0.50) were observed., Conclusions: Continuously applied SCS modulates expression of key genes involved in the regulation of neuronal membrane potential.

Background: Chronic opioid analgesic use often causes opioid-induced constipation (OIC). This open-label extension study evaluated the safety and efficacy of lubiprostone, a chloride channel (ClC-2) activator, for treatment of OIC in patients with chronic noncancer pain., Methods: Adults with OIC were enrolled from two 12-week, placebo-controlled, double-blind studies and received lubiprostone 24 μg twice daily for up to 9 months. OIC was defined as < 3 spontaneous bowel movements (SBMs)/week during the 2-week baseline period, of which ≥ 25% were characterized by hard to very hard stool consistency, subjectively incomplete evacuation, and/or moderate or worse straining. Inclusion criteria required consistent treatment with full opioid agonists ≥ 30 days prior to screening and throughout the study., Results: All 439 patients who received lubiprostone were analyzed for safety and efficacy. Overall, 24.6% of patients reported treatment-related adverse events (AEs), most commonly nausea (5.0%), diarrhea (4.6%), headache (1.6%), and vomiting (1.4%). No treatment-related serious AEs were reported. Nausea and diarrhea each led to study discontinuation in 5 patients (1.1%); 2 cases each of nausea and diarrhea were rated as severe. Rescue medication usage decreased from month 1 (33.0%) to month 9 (18.6%). Mean weekly SBM frequency (1.4) was significantly increased from baseline at all months (P < 0.001, range 4.9 to 5.3). Straining, abdominal bloating, abdominal discomfort, stool consistency, constipation severity, and bowel habit regularity were significantly improved from baseline at all months (P < 0.001)., Conclusions: Lubiprostone treatment was well tolerated and improved symptoms and signs of OIC in this 9-month, open-label study of patients with chronic noncancer pain., (© 2015 World Institute of Pain.)

Background: Pain relief with spinal cord stimulation (SCS) has focused historically on paresthesias overlapping chronically painful areas. A higher level evidence supports the use of SCS in treating leg pain than supports back pain, as it is difficult to achieve adequate paresthesia coverage, and then pain relief, in the low back region. In comparison, 10-kHz high-frequency (HF10 therapy) SCS therapy does not rely on intraoperative paresthesia mapping and remains paresthesia-free during therapy., Objective: To compare long-term results of HF10 therapy and traditional low-frequency SCS., Methods: A pragmatic randomized, controlled, pivotal trial with 24-month follow-up was conducted across 11 comprehensive pain treatment centers. Subjects had Visual Analog Scale scores of ≥5.0/10.0 cm for both back and leg pain, and were assigned randomly (1:1) to receive HF10 therapy or low-frequency SCS. The primary end point was a responder rate, defined as ≥50% back pain reduction from baseline at 3 months with a secondary end point at 12 months (previously reported). In this article, 24-month secondary results are presented. Non-inferiority was first assessed, and if demonstrated the results were tested for superiority., Results: In the study, 198 subjects were randomized (101 HF10 therapy, 97 traditional SCS). One hundred seventy-one subjects (90 HF10 therapy, 81 traditional SCS) successfully completed a short-term trial and were implanted. Subjects averaged 54.9 ± 12.9 years old, 13.6 ± 11.3 years since diagnosis, 86.6% had back surgery, 88.3% were taking opioid analgesics. At 3 months, 84.5% of implanted HF10 therapy subjects were responders for back pain and 83.1% for leg pain, and 43.8% of traditional SCS subjects were responders for back pain and 55.5% for leg pain (P < .001 for both back and leg pain comparisons, non-inferiority and superiority). At 24 months, more subjects were responders to HF10 therapy than traditional SCS (back pain: 76.5% vs 49.3%; 27.2% difference, 95% CI, 10.1%-41.8%; P < .001 for non-inferiority and superiority; leg pain: 72.9% vs 49.3%; 23.6% difference, 95% CI, 5.9%-38.6%; P < .001 for non-inferiority and P = .003 for superiority). Also at 24 months, back pain decreased to a greater degree with HF10 therapy (66.9% ± 31.8%) than traditional SCS (41.1% ± 36.8%, P < .001 for non-inferiority and superiority). Leg pain also decreased to a greater degree with HF10 therapy (65.1% ± 36.0%) than traditional SCS (46.0% ± 40.4%, P < .001 for non-inferiority and P = .002 for superiority)., Conclusion: This study demonstrates long-term superiority of HF10 therapy compared with traditional SCS in treating both back and leg pain. The advantages of HF10 therapy are anticipated to impact the management of chronic pain patients substantially., Abbreviations: IPG, implantable pulse generatorMCID, minimal clinically important differencePI, permanent implantODI, Oswestry Disability IndexSCS, spinal cord stimulationVAS, Visual Analog Scale.

Background: Few studies have evaluated single-gene changes modulated by spinal cord stimulation (SCS), providing a narrow understanding of molecular changes. Genomics allows for a robust analysis of holistic gene changes in response to stimulation., Methods: Rats were randomized into six groups to determine the effect of continuous SCS in uninjured and spared-nerve injury (SNI) animals. After behavioral assessment, tissues from the dorsal quadrant of the spinal cord (SC) and dorsal root ganglion (DRG) underwent full-genome microarray analyses. Weighted Gene Correlation Network Analysis (WGCNA), and Gene Ontology (GO) analysis identified similar expression patterns, molecular functions and biological processes for significant genes., Results: Microarray analyses reported 20,985 gene probes in SC and 19,104 in DRG. WGCNA sorted 7449 SC and 4275 DRG gene probes into 29 and 9 modules, respectively. WGCNA provided significant modules from paired comparisons of experimental groups. GO analyses reported significant biological processes influenced by injury, as well as the presence of an electric field. The genes Tlr2, Cxcl16, and Cd68 were used to further validate the microarray based on significant response to SCS in SNI animals. They were up-regulated in the SC while both Tlr2 and Cd68 were up-regulated in the DRG., Conclusions: The process described provides highly significant interconnected genes and pathways responsive to injury and/or electric field in the SC and DRG. Genes in the SC respond significantly to the SCS in both injured and uninjured animals, while those in the DRG significantly responded to injury, and SCS in injured animals., (© 2016 International Neuromodulation Society.)

Steroids are classified as endocrine disrupting chemicals; they are persistent with low biodegradability and are hardly degraded by conventional methods. Ozonation process has been effective for steroids degradation and the determination of the kinetics is a fundamental aspect for the design and operation of the reactor. This study assessed two methods: competitive kinetics and stopped flow, for determining the degradation kinetics of two steroids, estradiol (E2) and ethinylestradiol (EE2) in spiked water. Experiments were performed at pH 6, 21 °C, and using tertbutyl alcohol as scavenger of hydroxyl radicals; competitive kinetics method used sodium phenolate as reference compound. For the stopped flow, the experiments were performed in a BioLogic SFM-3000/S equipment. For both methods, the second order rate constants were in the order of 10(6) and 10(5) M(-1) s(-1) for E2 and EE2 respectively. The competitive kinetics can be applied with assurance and reliability but needing an additional analysis method to measure the residual concentrations. Stopped flow method allows the evaluation of the degradation kinetics in milliseconds and avoids the use of additional analytical methodologies; this method allows determining the reaction times on line. The methods are applicable for degradation of other emerging contaminants or other steroids and could be applied in water treatment at industrial level. Finally, it is important to consider the resources available to implement the most appropriate method, either competitive kinetics or the stopped-flow method.

Study Design: This study was a prospective, randomized, crossover, multicenter trial for the evaluation of comparative effectiveness of intradiscal biacuplasty (IDB) versus conventional medical management (CMM) in the treatment of lumbar discogenic pain., Objective: The objective was to demonstrate the superiority of IDB over CMM in the treatment of discogenic pain with respect to the primary outcome measure., Summary of Background Data: Current therapeutic options for the treatment of chronic low back pain of discogenic origin are limited. CMM is often unsatisfactory with regard to the treatment of discogenic pain. IDB offers a minimally invasive treatment that has been demonstrated to be superior to placebo in the past., Methods: A total of 63 subjects with lumbar discogenic pain diagnosed via provocation discography were randomized to IDB + CMM (n = 29) or CMM-alone (n = 34). At 6 months, patients in the CMM-alone group were eligible for crossover if desired. The primary outcome measure was the change in visual analog scale (VAS) from baseline to 6 months. Secondary outcome measures included treatment "responders," defined as the proportion of subjects with a 2-point or 30% decrease in VAS scores. Other secondary measures included changes from baseline to 6 months in (1) short form (SF) 36-physical functioning, (2) Oswestry Disability Index, (3) Beck Depression Inventory, (4) Patient Global Impression of Change, (5) EQ-5D VAS, and (6) back pain-related medication usage., Results: In the IDB cohort, the mean VAS score reduction exceeded that in the CMM cohort (-2.4 vs. -0.56; P = 0.02), and the proportion of treatment responders was substantially greater (50% vs. 18%). Differences in secondary measures favored IDB. No differences in opioid utilization were noted between groups., Conclusion: Superior performance of IDB with respect to all study outcomes suggests that it is a more effective treatment for discogenic pain than CMM-alone., Level of Evidence: 2.

Two cultivars of Japanese parsley were harvested in different seasons; their antioxidant capacities were evaluated by oxygen radical absorbance capacity (ORAC) methods, and the contents of hydrophilic and lipophilic antioxidants were compared. Japanese parsley possessed potent antioxidant capacities both in hydrophilic and lipophilic extracts when evaluated by ORAC methods. LC/MS/MS analyses revealed that chlorogenic acid and four kinds of quercetin glycosides were major antioxidants in the hydrophilic extract. Lutein was the main contributor to the antioxidant capacity of the lipophilic extract. Antioxidant capacities of the hydrophilic extracts of both cultivars tended to be higher in winter because of the increase in the contents of chlorogenic acid and quercetin glycosides. An obvious trend in the lipophilic antioxidant capacities or lutein contents was not observed irrespective of the cultivar.

Background: Perioperative management of patients on anticoagulant therapy prior to interventional pain procedures creates a challenge when balancing the risk of bleeding against thromboembolic events., Case Report: We report a case of epidural hematoma formation in the cervical spine following interlaminar epidural steroid injection in an elderly woman with chronic neck and arm pain, who was on clopidogrel therapy., Conclusions: This is the first reported case of hematoma formation immediately following an epidural steroid injection possibly associated with clopidogrel, even though established guidelines on the timing of the discontinuation of clopidogrel prior to the procedure were exceeded. Severe pain appears to be the first symptom of hematoma formation, and therefore immediate diagnostic workup and evacuation of hematoma are essential in preventing neurological damage. It may be advisable to carry out a test specific for clopidogrel such as the P2Y12 to ensure that there is no residual action on platelet aggregation function, particularly in patients who may be slow metabolizers of clopidogrel. Caution is advised prior to administering analgesics with antiplatelet effects such as ketorolac.

Introduction: Pulse frequency (Fc) is one of the most important parameters in neurostimulation, with Pulse Amplitude (Pw) and Amplitude (I). Up to certain Fc, increasing the number of pulses will generate action potentials in neighboring neural structures and may facilitate deeper penetration of the electromagnetic fields. In addition, changes in frequency modify the patient's sensation with stimulation., Materials/methods: Fifty patients previously implanted with rechargeable current control spinal cord stimulation. With pulse width fixed at 300 μsec, we stimulated at 26 different Fc values between 40 and 1200 Hz and determine the influence of these changes on different stimulation thresholds: perception threshold (Tp ), therapeutic perception (Tt), and discomfort threshold (Td). Simultaneously, paresthesia coverage of the painful area and patient's sensation and satisfaction related to the quality of stimulation were recorded., Results: Pulse Fc is inversely proportional to stimulation thresholds and this influence is statistically significant (p < 0.05). As Pulse Fc increased from 40 to 1200 Hz, the mean threshold decreases from 7.25 to 1.38 mA (Tp ), 8.17 to 1.63 (Tt ), and 9.20 to 1.85 (Td). Significant differences for Tp and Tt began at 750 Hz (Tp , Tt ) and at 650 Hz for Td. No significant influence was found regarding paresthesia coverage. As expected, Fc affects significantly patient's sensation and satisfaction., Discussion: Changes in Fc affect the quality of paresthesias. Within the evaluated parameters higher frequencies are inversely proportional to stimulation thresholds and Tt. It seems that Fc is a vital parameter to achieve therapeutic success., Conclusions: Changes in Fc is a useful parameter to modulate the patient's sensory perception. Fc can be successfully used to adjust the quality of the paresthesias and to modify patient's subjective sensation. We showed that as the frequency increases, the patient's satisfaction with the perceived sensation decreases, suggesting that higher Fc may need to be set up at subthreshold amplitude to achieve positive response., (© 2016 International Neuromodulation Society.)

Introduction: Currently available central nervous system treatment strategies are often insufficient in management of peripheral neuropathic pain, prompting a resurgence of neuromodulation focused on peripheral pain. A new peripheral nerve stimulation device was investigated in a prospective, randomized, double blind, crossover study, looking specifically at efficacy and safety, with Food and Drug Administration oversight., Methods: Prospective, multicenter, randomized, double-blind, partial crossover study to assess safety and efficacy. After IRB approval, patients were enrolled, implanted, and then followed for three months to assess efficacy and one year for safety based on Food and Drug Administration guidance., Results: One hundred forty-seven patients were consented and screened for the study. Thirty-five did not meet inclusion or exclusion criteria. Ninety-four patients were implanted and then randomized to the treatment (45) or the Control group (49). The primary efficacy endpoint, three months after randomization to treatment, demonstrated that patients receiving active stimulation achieved a statistically significantly higher response rate of 38% vs. the 10% rate found in the Control group (p = 0.0048). Improvement in pain was statistically significant between the randomized groups, with the Treatment group achieving a mean pain reduction of 27.2% from Baseline to Month 3 compared to a 2.3% reduction in the Control group (p < 0.0001). During the partial crossover period, patients again demonstrated statistically significant improvement in pain relief with active stimulation compared to baseline. Further, the Treatment group had significantly better improvement than the Control group in secondary measures including but not limited to quality of life and satisfaction. Safety, assessed throughout the trial and with follow-up to one year, demonstrated no serious adverse events related to the device. All device-related adverse events were minor and self-limiting., Conclusion: The novel peripheral nerve stimulation device is a safe and effective treatment strategy to address neuropathic pain of peripheral nerve origin., (© 2016 International Neuromodulation Society.)

Background: Chronic neuropathic pain has been recognized as contributing to a significant proportion of chronic pain globally. Among these, spinal pain is of significance with failed back surgery syndrome (FBSS), generating considerable expense for the health care systems with increasing prevalence and health impact., Objective: To assess the role and effectiveness of spinal cord stimulation (SCS) in chronic spinal pain., Study Design: A systematic review of randomized controlled trials (RCTs) of SCS in chronic spinal pain., Methods: The available literature on SCS was reviewed. The quality assessment criteria utilized were Cochrane review criteria to assess sources of risk of bias and Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment (IPM - QRB) criteria for randomized trials.The level of evidence was based on a best evidence synthesis with modified grading of qualitative evidence from Level I to Level V.Data sources included relevant literature published from 1966 through March 2015 that were identified through searches of PubMed and EMBASE, manual searches of the bibliographies of known primary and review articles, and all other sources., Outcome Measures: RCTs of efficacy with a minimum 12-month follow-up were considered for inclusion. For trials of adaptive stimulation, high frequency stimulation, and burst stimulation, shorter follow-up periods were considered., Results: Results showed 6 RCTs with 3 efficacy trials and 3 stimulation trials. There were also 2 cost effectiveness studies available. Based on a best evidence synthesis with 3 high quality RCTs, the evidence of efficacy for SCS in lumbar FBSS is Level I to II. The evidence for high frequency stimulation based on one high quality RCT is Level II to III. Based on a lack of high quality studies demonstrating the efficacy of adaptive stimulation or burst stimulation, evidence is limited for these 2 modalities., Limitations: The limitations of this systematic review continue to require future studies illustrating effectiveness and also the superiority of high frequency stimulation and potentially burst stimulation., Conclusion: There is significant (Level I to II) evidence of the efficacy of spinal cord stimulation in lumbar FBSS; whereas, there is moderate (Level II to III) evidence for high frequency stimulation; there is limited evidence for adaptive stimulation and burst stimulation.

Background: Epidural injections have been used since 1901 in managing low back pain and sciatica. Spinal pain, disability, health, and economic impact continue to increase, despite numerous modalities of interventions available in managing chronic spinal pain. Thus far, systematic reviews performed to assess the efficacy of epidural injections in managing chronic spinal pain have yielded conflicting results., Objective: To evaluate and update the clinical utility of the efficacy of epidural injections in managing chronic spinal pain., Study Design: A systematic review of randomized controlled trials of epidural injections in managing chronic spinal pain., Methods: In this systematic review, randomized trials with a placebo control or an active-control design were included. The outcome measures were pain relief and functional status improvement. The quality of each individual article was assessed by Cochrane review criteria, as well as the Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB). Best evidence synthesis was conducted based on the qualitative level of evidence (Level I to V). Data sources included relevant literature identified through searches of PubMed for a period starting in 1966 through August 2015; Cochrane reviews; and manual searches of the bibliographies of known primary and review articles., Results: A total of 52 trials met inclusion criteria. Meta-analysis was not feasible. The evidence in managing lumbar disc herniation or radiculitis is Level II for long-term improvement either with caudal, interlaminar, or transforaminal epidural injections with no significant difference among the approaches. The evidence is Level II for long-term management of cervical disc herniation with interlaminar epidural injections. The evidence is Level II to III in managing thoracic disc herniation with an interlaminar approach. The evidence is Level II for caudal and lumbar interlaminar epidural injections with Level III evidence for lumbar transforaminal epidural injections for lumbar spinal stenosis. The evidence is Level III for cervical spinal stenosis management with an interlaminar approach. The evidence is Level II for axial or discogenic pain without facet arthropathy or disc herniation treated with caudal or lumbar interlaminar injections in the lumbar region; whereas it is Level III in the cervical region treated with cervical interlaminar epidural injections. The evidence for post lumbar surgery syndrome is Level II with caudal epidural injections and for post cervical surgery syndrome it is Level III with cervical interlaminar epidural injections., Limitations: Even though this is a large systematic review with inclusion of a large number of randomized controlled trials, the paucity of high quality randomized trials literature continues to confound the evidence., Conclusion: This systematic review, with an assessment of the quality of manuscripts and outcome parameters, shows the efficacy of epidural injections in managing a multitude of chronic spinal conditions.

Background: Current treatments for chronic pain have limited effectiveness and commonly known side effects. Given the prevalence and burden of intractable pain, additional therapeutic approaches are desired. Spinal cord stimulation (SCS) delivered at 10 kHz (as in HF10 therapy) may provide pain relief without the paresthesias typical of traditional low-frequency SCS. The objective of this randomized, parallel-arm, noninferiority study was to compare long-term safety and efficacy of SCS therapies in patients with back and leg pain., Methods: A total of 198 subjects with both back and leg pain were randomized in a 1:1 ratio to a treatment group across 10 comprehensive pain treatment centers. Of these, 171 passed a temporary trial and were implanted with an SCS system. Responders (the primary outcome) were defined as having 50% or greater back pain reduction with no stimulation-related neurological deficit., Results: At 3 months, 84.5% of implanted HF10 therapy subjects were responders for back pain and 83.1% for leg pain, and 43.8% of traditional SCS subjects were responders for back pain and 55.5% for leg pain (P < 0.001 for both back and leg pain comparisons). The relative ratio for responders was 1.9 (95% CI, 1.4 to 2.5) for back pain and 1.5 (95% CI, 1.2 to 1.9) for leg pain. The superiority of HF10 therapy over traditional SCS for leg and back pain was sustained through 12 months (P < 0.001). HF10 therapy subjects did not experience paresthesias., Conclusion: HF10 therapy promises to substantially impact the management of back and leg pain with broad applicability to patients, physicians, and payers.

Background: The therapeutic spinal facet joint interventions generally used for the treatment of axial spinal pain of facet joint origin are intraarticular facet joint injections, facet joint nerve blocks, and radiofrequency neurotomy. Despite interventional procedures being common as treatment strategies for facet joint pathology, there is a paucity of literature investigating these therapeutic approaches. Systematic reviews assessing the effectiveness of various therapeutic facet joint interventions have shown there to be variable evidence based on the region and the modality of treatment utilized. Overall, the evidence ranges from limited to moderate., Objective: To evaluate and update the clinical utility of therapeutic lumbar, cervical, and thoracic facet joint interventions in managing chronic spinal pain., Study Design: A systematic review of therapeutic lumbar, cervical, and thoracic facet joint interventions for the treatment of chronic spinal pain., Methods: The available literature on lumbar, cervical, and thoracic facet joint interventions in managing chronic spinal pain was reviewed. The quality assessment criteria utilized were the Cochrane Musculoskeletal Review Group criteria and Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) for randomized trials and Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies (IPM-QRBNR) for observational studies. The level of evidence was classified at 5 levels from Level I to Level V. Data sources included relevant literature identified through searches on PubMed and EMBASE from 1966 through March 2015, and manual searches of the bibliographies of known primary and review articles., Outcome Measures: The primary outcome measure was pain relief (short-term relief = up to 6 months and long-term > 6 months). Secondary outcome measures were improvement in functional status, psychological status, return to work, and reduction in opioid intake consumption., Results: A total of 21 randomized controlled trials meeting appropriate inclusion criteria were assessed in this evaluation. A total of 5 observational studies were assessed. In the lumbar spine, for long-term effectiveness, there is Level II evidence for radiofrequency neurotomy and lumbar facet joint nerve blocks, whereas the evidence is Level III for lumbosacral intraarticular injections. In the cervical spine, for long-term improvement, there is Level II evidence for cervical radiofrequency neurotomy and cervical facet joint nerve blocks, and Level IV evidence for cervical intraarticular injections. In the thoracic spine there is Level II evidence for thoracic facet joint nerve blocks and Level IV evidence for radiofrequency neurotomy for long-term improvement., Limitations: The limitations of this systematic review include an overall paucity of high quality studies and more specifically the lack of investigations related to thoracic facet joint injections., Conclusion: Based on the present assessment for the management of spinal facet joint pain, the evidence for long-term improvement is Level II for lumbar and cervical radiofrequency neurotomy, and therapeutic facet joint nerve blocks in the cervical, thoracic, and lumbar spine; Level III for lumbar intraarticular injections; and Level IV for cervical intraarticular injections and thoracic radiofrequency neurotomy.

Objectives: Models that simulate clinical conditions are needed to gain an understanding of the mechanism involved during spinal cord stimulation (SCS) treatment of chronic neuropathic pain. An animal model has been developed for continuous SCS in which animals that have been injured to develop neuropathic pain behavior were allowed to carry on with regular daily activities while being stimulated for 72 hours., Material and Methods: Sprague-Dawley rats were randomized into each of six different groups (N = 10-13). Three groups included animals in which the spared nerve injury (SNI) was induced. Animals in two of these groups were implanted with a four-contact electrode in the epidural space. Animals in one of these groups received stimulation for 72 hours continuously. Three corresponding sham groups (no SNI) were included. Mechanical and cold-thermal allodynia were evaluated using von Frey filaments and acetone drops, respectively. Mean withdrawal thresholds were compared. Statistical significance was established using one-way ANOVAs followed by Holm-Sidak post hoc analysis., Results: Continuous SCS attenuates mechanical allodynia in animals with neuropathic pain behavior. Mechanical withdrawal threshold increases significantly in SNI animals after 24 and 72 hours stimulation vs. SNI no stimulation (p = 0.007 and p < 0.001, respectively). SCS for 24 and 72 hours provides significant increase in mechanical withdrawal thresholds relative to values before stimulation (p = 0.001 and p < 0.001, respectively). Stimulation did not provide recovery to baseline values. SCS did not seem to attenuate cold-thermal allodynia., Conclusion: A continuous SCS model has been developed. Animals with neuropathic pain behavior that were continuously stimulated showed significant increase in withdrawal thresholds proportional to stimulation time., (© 2015 International Neuromodulation Society.)

Objective: To evaluate the efficacy and safety of oral lubiprostone for relieving symptoms of opioid-induced constipation (OIC) in patients with chronic noncancer pain., Design: Prospective, randomized, double-blind, placebo-controlled trial., Setting: Seventy-nine US and Canadian centers., Subjects: Patients aged ≥ 18 years with OIC, defined as <3 spontaneous bowel movements (SBMs) per week., Methods: Patients received lubiprostone 24 mcg or placebo twice daily for 12 weeks. The primary endpoint was change from baseline in SBM frequency at week 8., Results: Among randomized patients (N=418; lubiprostone, N=210; placebo, N=208), most completed the study (lubiprostone, 67.1%; placebo, 69.7%). The safety and efficacy (intent-to-treat) populations included 414 (lubiprostone, N=208; placebo, N=206) and 413 (lubiprostone, N=209; placebo, N=204) patients, respectively. The mean (standard deviation) age was 50.4 (10.9) years; most patients were female (64.4%) and white (77.7%). Changes from baseline in SBM frequency rates were significantly higher at week 8 (P=0.005) and overall (P=0.004) in patients treated with lubiprostone compared with placebo. Pairwise comparisons showed significantly greater overall improvement for abdominal discomfort (P=0.047), straining (P<0.001), constipation severity (P=0.007), and stool consistency (P<0.001) with lubiprostone compared with placebo. Moreover, patients rated the effectiveness of lubiprostone as significantly (P<0.05) better than placebo for 11 of 12 weeks. The most common treatment-related adverse events (AEs) with lubiprostone and placebo were nausea (16.8% vs 5.8%, respectively), diarrhea (9.6% vs 2.9%), and abdominal distention (8.2% vs 2.4%). No lubiprostone-related serious AEs occurred., Conclusion: Lubiprostone effectively relieved OIC and associated signs and symptoms and was well tolerated in patients with chronic noncancer pain (http://clinicaltrials.gov/ct2/show/NCT00595946)., (© 2014 The Authors. Pain Medicine published by Wiley Periodicals, Inc. on behalf of American Academy of Pain Medicine.)

Background and Objectives: Radiofrequency (RF) neuroablation is a common therapy for alleviating chronic pain. Larger lesion volumes lead to higher chance of ablating small sensory nerves; therefore, bipolar-RF and cooled-RF are improved alternatives to conventional monopolar-RF. This work provides an ex vivo comparison of bipolar-RF to cooled-RF lesioning in the presence of bone structure using some conventional temperature and time programs and in conjunction with injection of a variety of clinically used substances., Methods: Studies were performed using chicken muscle near a bone structure. Cooled-RF was applied using standard parameters at 60°C for 150 seconds and perpendicular to the bone. Bipolar-RF was applied using interelectrode distances (IEDs) of 5, 10, or 15 mm at 80°C for 90 or 150 seconds with the electrodes positioned either paralleled between the bone and muscle or perpendicular to the bone. The effect of injection of various fluids (sterile water, 0.9% saline, 7.3% saline, 2% lidocaine, 0.25% bupivacaine, lidocaine/methylprednisolone (Depo-Medrol), or lidocaine/betamethasone (Celestone) on lesion size was compared with no fluid injected in the muscle. Temperature profiles of lesioning were also obtained using an infrared camera., Results: The volume of bipolar-RF lesions is dependent on IED, being more favorable at IED equals 10 mm. The injection of some fluids induces significant (P < 0.05) changes in bipolar-RF lesion volume, although the changes are dependent on IED. Cooled-RF induces larger lesions than bipolar-RF, with no changes in volume induced by injecting fluids., Conclusions: Cooled-RF yields larger lesions than bipolar-RF under the conditions used in this study. The spherical shape of cooled-RF lesions provides larger volume coverage than lesions obtained with bipolar-RF at IED equals 5, 10, or 15 mm under similar electrode tip temperature and lesioning time.

Background: A major component of a systematic review is an assessment of the methodological quality and bias of randomized trials. The most commonly utilized methodological quality assessment and bias assessment for randomized trials is by the Cochrane Review Group. While this is not a "gold standard," it is an indication of the current state-of-the-art review methodology. There is, however, no specific instrument to assess the methodological quality of manuscripts published for interventional techniques., Objectives: Our objective was to develop an instrument specifically for interventional pain management, to assess the methodological quality of randomized trials of interventional techniques., Methods: Item generation for the instrument was based on a definition of quality, to the extent to which the design and conduct of the trial were congruent with the objectives of the trial. Applicability was defined as the extent to which the trial produced procedures could be applied with contemporary interventional pain management techniques. Multiple items based on Cochrane review criteria were utilized along with specific requirements for interventional techniques., Results: A total of 22 items were developed which formed IPM-QRB or Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment tool. This included 9 of the 12 items from the Cochrane review criteria with definition of some items that were repetitive or duplicate, and the addition of 13 new items. The results were compared for inter-rater reliability of Cochrane review criteria and IPM-QRB, and inter-instrument reliability. The assessment was performed in multiple stages with an initial learning curve. The final assessment was for 4 randomized controlled trials (RCTs) utilizing both Cochrane review criteria and IPM-QRB criteria. The inter-rater agreement for Cochrane review criteria with overall intra-class correlation coefficient was 0.407 compared to an intra-class correlation coefficient of 0.833 for IPM-QRB criteria. The inter-rater agreement was superior for IPM-QRB criteria compared to Cochrane review criteria despite twice the items of Cochrane review criteria as IPM-QRB criteria with the detailed nature of assessment., Limitations: Limited validity or accuracy assessment of the instrument and the large number of items to be scored., Conclusion: We have developed a new comprehensive instrument to assess the methodological quality of randomized trials of interventional techniques. This instrument is superior to Cochrane review methodology criteria in that it provides more extensive and specific information for interventional techniques that will be useful in assessing the methodologic quality and bias of interventional techniques.

Background: The major component of a systematic review is assessment of the methodologic quality and bias of randomized and nonrandomized trials. While there are multiple instruments available to assess the methodologic quality and bias for randomized controlled trials (RCTs), there is a lack of extensively utilized instruments for observational studies, specifically for interventional pain management (IPM) techniques. Even Cochrane review criteria for randomized trials is considered not to be a "gold standard," but merely an indication of the current state of the art review methodology. Recently a specific instrument to assess the methodologic quality of randomized trials has been developed for interventional techniques., Objectives: Our objective was to develop an IPM specific instrument to assess the methodological quality of nonrandomized trials or observational studies of interventional techniques., Methods: The item generation for the instrument was based on a definition of quality, to the extent to which the design and conduct of the trial were congruent with the objectives of the study. Applicability was defined as the extent to which procedures produced by the study could be applied using contemporary IPM techniques. Multiple items based on Cochrane review criteria and Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies (IPM-QRBNR) were utilized., Results: A total of 16 items were developed which formed the IPM-QRBNR tool. The assessment was performed in multiple stages. The final assessment was 4 nonrandomized studies. The inter-rater agreement was moderate to good for IPM-QRBNR criteria., Limitations: Limited validity or accuracy assessment of the instrument and the large number of items to be scored were limitations., Conclusion: We have developed a new comprehensive instrument to assess the methodological quality of nonrandomized studies of interventional techniques. This instrument provides extensive information specific to interventional techniques is useful in assessing the methodological quality and bias of observational studies of interventional techniques.

Background: Pulsed radiofrequency (PRF) therapy is a clinical treatment utilizing electromagnetic energy aimed to relieve neuropathic pain. This is the first study examining the modulated expression of pain regulatory genes following the induction of the spared nerve injury (SNI) pain model and subsequently treated with PRF therapy., Objectives: The present study investigated the behavioral efficacy of PRF therapy in rats exhibiting sciatic nerve injury and examined gene expression changes in the sciatic nerve, ipsilateral L5 dorsal root ganglia (DRG), and spinal cord., Study Design: A randomized, experimental trial., Setting: Department of Biological Sciences, Illinois State University and Department of Psychology, Illinois Wesleyan University., Methods: An SNI model was used in male Sprague-Dawley rats (weight 260-310 g). A sham surgery was also performed as a control group. After 3 days development of the SNI model, an RF electrode was applied to the sciatic nerve proximal to the site of injury and stimulated for 3 minutes. The response to mechanical stimuli was assessed throughout the duration of the study. Furthermore, changes in gene expression along the nociceptive tract (sciatic nerve, DRG, and spinal cord) were assessed 24 hours post-PRF therapy., Results: It was observed that the mechanical allodynia, induced by SNI model, was reversed to control values within 24 hours post-PRF therapy. Additionally, modulated expression of pain regulatory genes was observed after induction of the SNI model. Following PRF therapy, expression of many of these genes returned to control values (sham) in each of the tissues tested. Increased proinflammatory gene expression, such as TNF-α and IL-6, observed in the sciatic nerve (site of injury) in the SNI group was returned to baseline values following PRF therapy. Up-regulation of GABAB-R1, Na/K ATPase, and 5-HT3r as well as down regulation of TNF-α and IL-6 were also observed in the DRG in the SNI-PRF group relative to the SNI group. Up-regulation of Na/K ATPase and c-Fos was found in the spinal cord following PRF treatment relative to the SNI group., Limitations: Immediate changes in gene expression were observed at 24 hours to better determine the mechanism with no long-term data at this time. Protein expression was not assessed in addition to gene expression changes., Conclusion: These results indicate that the electromagnetic energy applied via PRF therapy influences the reversal of behavioral and molecular effects of hypersensitivity developed from a peripheral nerve injury.

Objectives: To examine the feasibility of novel high-frequency spinal cord stimulation therapy in a cohort of patients with chronic predominant back pain during a four day, percutaneous trial., Design: Prospective, multicenter open label pilot trial., Setting and Patients:  Twenty-four patients with back pain greater than leg pain who were candidates for spinal cord stimulation were trialed at five U.S. centers., Interventions: Patients completed a percutaneous trial with a commercially available spinal cord stimulator. The implanted leads were then connected to the novel external stimulation device and patients were trialed for an additional four days., Outcome Measures: Pain intensity ratings, subjective descriptions, and patients' preference., Results: There was significant improvement from baseline in overall pain scores (8.68 to 2.03, [p < 0.001]) and back pain scores (8.12 to 1.88, [p < 0.001]) with the investigational stimulation. The investigational stimulation was preferred to the commercially available systems in 21 of 24 patients (88%)., Conclusions: Patients with predominant back pain reported a substantial reduction in overall pain and back pain when trialed with high-frequency spinal cord stimulation therapy., (© 2013 International Neuromodulation Society.)

Objective: To develop evidence-based clinical practice guidelines for interventional techniques in the diagnosis and treatment of chronic spinal pain., Methodology: Systematic assessment of the literature., Evidence: I. Lumbar Spine • The evidence for accuracy of diagnostic selective nerve root blocks is limited; whereas for lumbar provocation discography, it is fair. • The evidence for diagnostic lumbar facet joint nerve blocks and diagnostic sacroiliac intraarticular injections is good with 75% to 100% pain relief as criterion standard with controlled local anesthetic or placebo blocks. • The evidence is good in managing disc herniation or radiculitis for caudal, interlaminar, and transforaminal epidural injections; fair for axial or discogenic pain without disc herniation, radiculitis or facet joint pain with caudal, and interlaminar epidural injections, and limited for transforaminal epidural injections; fair for spinal stenosis with caudal, interlaminar, and transforaminal epidural injections; and fair for post surgery syndrome with caudal epidural injections and limited with transforaminal epidural injections. • The evidence for therapeutic facet joint interventions is good for conventional radiofrequency, limited for pulsed radiofrequency, fair to good for lumbar facet joint nerve blocks, and limited for intraarticular injections. • For sacroiliac joint interventions, the evidence for cooled radiofrequency neurotomy is fair; limited for intraarticular injections and periarticular injections; and limited for both pulsed radiofrequency and conventional radiofrequency neurotomy. • For lumbar percutaneous adhesiolysis, the evidence is fair in managing chronic low back and lower extremity pain secondary to post surgery syndrome and spinal stenosis. • For intradiscal procedures, the evidence for intradiscal electrothermal therapy (IDET) and biaculoplasty is limited to fair and is limited for discTRODE. • For percutaneous disc decompression, the evidence is limited for automated percutaneous lumbar discectomy (APLD), percutaneous lumbar laser disc decompression, and Dekompressor; and limited to fair for nucleoplasty for which the Centers for Medicare and Medicaid Services (CMS) has issued a noncoverage decision. II. Cervical Spine • The evidence for cervical provocation discography is limited; whereas the evidence for diagnostic cervical facet joint nerve blocks is good with a criterion standard of 75% or greater relief with controlled diagnostic blocks. • The evidence is good for cervical interlaminar epidural injections for cervical disc herniation or radiculitis; fair for axial or discogenic pain, spinal stenosis, and post cervical surgery syndrome. • The evidence for therapeutic cervical facet joint interventions is fair for conventional cervical radiofrequency neurotomy and cervical medial branch blocks, and limited for cervical intraarticular injections. III. Thoracic Spine • The evidence is limited for thoracic provocation discography and is good for diagnostic accuracy of thoracic facet joint nerve blocks with a criterion standard of at least 75% pain relief with controlled diagnostic blocks. • The evidence is fair for thoracic epidural injections in managing thoracic pain. • The evidence for therapeutic thoracic facet joint nerve blocks is fair, limited for radiofrequency neurotomy, and not available for thoracic intraarticular injections. IV. Implantables • The evidence is fair for spinal cord stimulation (SCS) in managing patients with failed back surgery syndrome (FBSS) and limited for implantable intrathecal drug administration systems. V. ANTICOAGULATION • There is good evidence for risk of thromboembolic phenomenon in patients with antithrombotic therapy if discontinued, spontaneous epidural hematomas with or without traumatic injury in patients with or without anticoagulant therapy to discontinue or normalize INR with warfarin therapy, and the lack of necessity of discontinuation of nonsteroidal anti-inflammatory drugs (NSAIDs), including low dose aspirin prior to performing interventional techniques. • There is fair evidence with excessive bleeding, including epidural hematoma formation with interventional techniques when antithrombotic therapy is continued, the risk of higher thromboembolic phenomenon than epidural hematomas with discontinuation of antiplatelet therapy prior to interventional techniques and to continue phosphodiesterase inhibitors (dipyridamole, cilostazol, and Aggrenox). • There is limited evidence to discontinue antiplatelet therapy with platelet aggregation inhibitors to avoid bleeding and epidural hematomas and/or to continue antiplatelet therapy (clopidogrel, ticlopidine, prasugrel) during interventional techniques to avoid cerebrovascular and cardiovascular thromboembolic fatalities. • There is limited evidence in reference to newer antithrombotic agents dabigatran (Pradaxa) and rivaroxan (Xarelto) to discontinue to avoid bleeding and epidural hematomas and are continued during interventional techniques to avoid cerebrovascular and cardiovascular thromboembolic events., Conclusions: Evidence is fair to good for 62% of diagnostic and 52% of therapeutic interventions assessed., Disclaimer: The authors are solely responsible for the content of this article. No statement on this article should be construed as an official position of ASIPP. The guidelines do not represent "standard of care."

Background: Lumbar facet joints are a well recognized source of low back pain and referred pain in the lower extremity in patients with chronic low back pain. Conventional clinical features and other non-invasive diagnostic modalities are unreliable in diagnosing lumbar zygapophysial joint pain. Controlled diagnostic studies with at least 80% pain relief as the criterion standard have shown the prevalence of lumbar facet joint pain to be 16% to 41% of patients with chronic low back pain without disc displacement or radiculitis, with a false-positive rate of 17% to 49% with a single diagnostic block., Study Design: A systematic review of the diagnostic accuracy of lumbar facet joint nerve blocks., Objective: To determine and update the diagnostic accuracy of lumbar facet joint nerve blocks in the assessment of chronic low back pain., Methods: A methodological quality assessment of included studies was performed using Quality Appraisal of Reliability Studies (QAREL). Only diagnostic accuracy studies meeting at least 50% of the designated inclusion criteria were utilized for analysis. Studies scoring less than 50% are presented descriptively and analyzed critically. The level of evidence was classified as good, fair, and limited or poor based on the quality of evidence developed by the United States Preventive Services Task Force (USPSTF). Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to June 2012, and manual searches of the bibliographies of known primary and review articles., Outcome Measures: Studies must have been performed utilizing controlled local anesthetic blocks. Pain relief was categorized as at least 50% pain relief from baseline pain and the ability to perform previously painful movements., Results: A total of 25 diagnostic accuracy studies were included. Of these, one study evaluated 50% to 74% relief as criterion standard with a single block with prevalence of 48%, 4 studies evaluated 75% to 100% relief as the criterion standard with a single block with a prevalence of 31% to 61%, 5 studies evaluated 50% to 74% relief as the criterion standard with controlled blocks with a prevalence of 15% to 61%, and 13 studies evaluated 75% to 100% relief as the criterion standard with controlled blocks with a prevalence of 25% to 45% in heterogenous populations. False-positive rates ranged from 17% to 66% relief and 27% to 49% with at least 75% relief as the criterion standard. Based on this evaluation, the evidence showed that there is good evidence for diagnostic facet joint nerve blocks with 75% to 100% pain relief as the criterion standard with dual blocks and fair evidence with 50% to 74% pain relief as the criterion standard with controlled diagnostic blocks; however, the evidence is poor with single diagnostic blocks of 50% to 74%, and limited for 75% or more pain relief as the criterion standard., Limitations: The shortcomings of this systematic review of the accuracy of diagnostic lumbar facet joint nerve blocks include a paucity of literature and continued debate on an appropriate gold standard., Conclusion: There is good evidence for diagnostic facet joint nerve blocks with 75% to 100% pain relief as the criterion standard with dual blocks, with fair evidence with 50% to 74% pain relief.

Results: Part 2 of the guidelines on responsible opioid prescribing provides the following recommendations for initiating and maintaining chronic opioid therapy of 90 days or longer. 1. A) Comprehensive assessment and documentation is recommended before initiating opioid therapy, including documentation of comprehensive history, general medical condition, psychosocial history, psychiatric status, and substance use history. (, Evidence: good) B) Despite limited evidence for reliability and accuracy, screening for opioid use is recommended, as it will identify opioid abusers and reduce opioid abuse. (, Evidence: limited) C) Prescription monitoring programs must be implemented, as they provide data on patterns of prescription usage, reduce prescription drug abuse or doctor shopping. (, Evidence: good to fair) D) Urine drug testing (UDT) must be implemented from initiation along with subsequent adherence monitoring to decrease prescription drug abuse or illicit drug use when patients are in chronic pain management therapy. (, Evidence: good) 2. A) Establish appropriate physical diagnosis and psychological diagnosis if available prior to initiating opioid therapy. (, Evidence: good) B) Caution must be exercised in ordering various imaging and other evaluations, interpretation and communication with the patient, to avoid increased fear, activity restriction, requests for increased opioids, and maladaptive behaviors. (, Evidence: good) C) Stratify patients into one of the 3 risk categories - low, medium, or high risk. D) A pain management consultation, may assist non-pain physicians, if high-dose opioid therapy is utilized. (, Evidence: fair) 3. Essential to establish medical necessity prior to initiation or maintenance of opioid therapy. (, Evidence: good) 4. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. (, Evidence: good) 5. A) Long-acting opioids in high doses are recommended only in specific circumstances with severe intractable pain that is not amenable to short-acting or moderate doses of long-acting opioids, as there is no significant difference between long-acting and short-acting opioids for their effectiveness or adverse effects. (, Evidence: fair) B) The relative and absolute contraindications to opioid use in chronic non-cancer pain must be evaluated including respiratory instability, acute psychiatric instability, uncontrolled suicide risk, active or history of alcohol or substance abuse, confirmed allergy to opioid agents, coadministration of drugs capable of inducing life-limiting drug interaction, concomitant use of benzodiazepines, active diversion of controlled substances, and concomitant use of heavy doses of central nervous system depressants. (, Evidence: fair to limited) 6. A robust agreement which is followed by all parties is essential in initiating and maintaining opioid therapy as such agreements reduce overuse, misuse, abuse, and diversion. (, Evidence: fair) 7. A) Once medical necessity is established, opioid therapy may be initiated with low doses and short-acting drugs with appropriate monitoring to provide effective relief and avoid side effects. (, Evidence: fair for short-term effectiveness, limited for long-term effectiveness) B) Up to 40 mg of morphine equivalent is considered as low dose, 41 to 90 mg of morphine equivalent as a moderate dose, and greater than 91 mg of morphine equivalence as high dose. (, Evidence: fair) C) In reference to long-acting opioids, titration must be carried out with caution and overdose and misuse must be avoided. (, Evidence: good) 8. A) Methadone is recommended for use in late stages after failure of other opioid therapy and only by clinicians with specific training in the risks and uses. (, Evidence: limited) B) Monitoring recommendation for methadone prescription is that an electrocardiogram should be obtained prior to initiation, at 30 days and yearly thereafter. (, Evidence: fair) 9. In order to reduce prescription drug abuse and doctor shopping, adherence monitoring by UDT and PMDPs provide evidence that is essential to the identification of those patients who are non-compliant or abusing prescription drugs or illicit drugs. (, Evidence: fair) 10. Constipation must be closely monitored and a bowel regimen be initiated as soon as deemed necessary. (, Evidence: good) 11. Chronic opioid therapy may be continued, with continuous adherence monitoring, in well-selected populations, in conjunction with or after failure of other modalities of treatments with improvement in physical and functional status and minimal adverse effects. (, Evidence: fair)., Disclaimer: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

Background: Opioid abuse has continued to increase at an alarming rate since the 1990 s. As documented by different medical specialties, medical boards, advocacy groups, and the Drug Enforcement Administration, available evidence suggests a wide variance in chronic opioid therapy of 90 days or longer in chronic non-cancer pain. Part 1 describes evidence assessment., Objectives: The objectives of opioid guidelines as issued by the American Society of Interventional Pain Physicians (ASIPP) are to provide guidance for the use of opioids for the treatment of chronic non-cancer pain, to produce consistency in the application of an opioid philosophy among the many diverse groups involved, to improve the treatment of chronic non-cancer pain, and to reduce the incidence of abuse and drug diversion. The focus of these guidelines is to curtail the abuse of opioids without jeopardizing non-cancer pain management with opioids., Results: 1) There is good evidence that non-medical use of opioids is extensive; one-third of chronic pain patients may not use prescribed opioids as prescribed or may abuse them, and illicit drug use is significantly higher in these patients. 2) There is good evidence that opioid prescriptions are increasing rapidly, as the majority of prescriptions are from non-pain physicians, many patients are on long-acting opioids, and many patients are provided with combinations of long-acting and short-acting opioids. 3) There is good evidence that the increased supply of opioids, use of high dose opioids, doctor shoppers, and patients with multiple comorbid factors contribute to the majority of the fatalities. 4) There is fair evidence that long-acting opioids and a combination of long-acting and short-acting opioids contribute to increasing fatalities and that even low-doses of 40 mg or 50 mg of daily morphine equivalent doses may be responsible for emergency room admissions with overdoses and deaths. 5) There is good evidence that approximately 60% of fatalities originate from opioids prescribed within the guidelines, with approximately 40% of fatalities occurring in 10% of drug abusers. 6) The short-term effectiveness of opioids is fair, whereas the long-term effectiveness of opioids is limited due to a lack of long-term (> 3 months) high quality studies, with fair evidence with no significant difference between long-acting and short-acting opioids. 7) Among the individual drugs, most opioids have fair evidence for short-term and limited evidence for long-term due to a lack of quality studies. 8) The evidence for the effectiveness and safety of chronic opioid therapy in the elderly for chronic non-cancer pain is fair for short-term and limited for long-term due to lack of high quality studies; limited in children and adolescents and patients with comorbid psychological disorders due to lack of quality studies; and the evidence is poor in pregnant women. 9) There is limited evidence for reliability and accuracy of screening tests for opioid abuse due to lack of high quality studies. 10) There is fair evidence to support the identification of patients who are non-compliant or abusing prescription drugs or illicit drugs through urine drug testing and prescription drug monitoring programs, both of which can reduce prescription drug abuse or doctor shopping., Disclaimer: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

Background: There is a paucity of literature on the use of epidural injections for the treatment of chronic mid and upper back pain due to disc herniation and radiculitis, axial or discogenic pain, spinal stenosis, post surgery syndrome, and post thoracotomy pain syndrome., Study Design: A systematic review of therapeutic thoracic epidural injection therapy for chronic mid and upper back pain., Objective: The objective of this systematic review is to determine the effects of thoracic interlaminar epidural injections with or without steroids, with or without fluoroscopy, and for various conditions including disc herniation and radiculitis, axial or discogenic pain, spinal stenosis, post thoracic surgery syndrome, and post thoracotomy pain syndrome., Methods: The available literature on thoracic interlaminar epidural injections with or without steroids in managing various types of chronic mid and upper back pain was reviewed. The quality assessment and clinical relevance criteria utilized were the Cochrane Musculoskeletal Review Group criteria as utilized for interventional techniques for randomized trials and the criteria developed by the Newcastle-Ottawa Scale criteria for observational studies. The level of evidence was classified as good, fair, or limited (or poor) based on the quality of evidence developed by the U.S. Preventive Services Task Force (USPSTF). Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to March 2012, and manual searches of the bibliographies of known primary and review articles., Outcome Measures: The primary outcome measure was pain relief (short-term relief = up to 6 months and long-term > 6 months). Secondary outcome measures were improvement in functional status, psychological status, return to work, and reduction in opioid intake., Results: For this review, 17 studies were identified, including studies examining adverse reactions. Only 2 studies were included: one randomized trial and one non-randomized or observational study. The results of this systematic review evaluating the effectiveness of thoracic epidural injections with or without steroids in managing chronic thoracic pain shows fair evidence with one randomized trial in patients with various causes; whereas the evidence is limited based on one non-randomized study evaluating chronic pain in post thoracotomy syndrome., Limitations: The limitations of this study include paucity of evidence., Conclusion: The evidence based on this systematic review for thoracic epidural injection in treating chronic thoracic pain is considered fair and limited for post thoracotomy pain.

Background: Lumbar spinal stenosis (LSS) generally occurs from a combination of degenerative changes occurring in the lumbar spine. These include hypertrophy of ligamentum flavum, facet joint arthritic changes and bulging of the intervertebral disk. Spinal stenosis leads to compression of the lumbar neural elements (cauda equina), which manifests as low back and leg pain especially on standing and walking known as "neurogenic claudication." Current treatment options for LSS are varied. Conservative management, including physical therapy with/without epidural steroid injections, may be adequate for mild stenosis. Surgical decompression is reserved for severe cases and results in variable degrees of success. Patients with moderate-to-severe LSS having ligamentum flavum hypertrophy as a key contributor are generally inappropriately treated or undertreated. This is due to ineffectiveness of conservative therapy and possibility that major surgical compression might be too aggressive. Percutaneous decompression offers a possible solution for this patient population., Methods: One-year follow-up study was conducted at 11 U.S. sites. Study cohort included 58 mild(®) percutaneous decompression patients who underwent 170 procedures, the majority treated bilaterally at one or two lumbar levels. Outcome measures included the visual analog scale (VAS), Oswestry Disability Index (ODI), Zurich Claudication Questionnaire (ZCQ), and SF-12v2(®) Health Survey., Results: No major mild(®) device or procedure-related complications were reported. One-year data showed significant reduction of pain as measured by VAS. Improvement in physical functionality, mobility, and disability was significant as measured by ZCQ, SF-12v2, and ODI., Conclusions: At 1 year this 58-patient cohort demonstrated continued excellent safety profile of the mild(®) procedure and equally important, showed long-term pain relief and improved functionality., (© 2011 The Authors. Pain Practice © 2011 World Institute of Pain.)

Introduction: In a prospective observational study conducted in an urban pain management center, we evaluated whether spinal cord stimulation (SCS) is effective in relieving discogenic pain of IDD origin., Methods: Thirteen patients with intractable discogenic low back pain were enrolled. Four patients never underwent permanent implantation due to insurance denial, medical reasons or failed trial and served as a control group. Nine patients underwent SCS implantation (treatment group). All patients were followed for 12 months and assessed at each interval for pain (NRS), disability (ODI), and opioid use., Results: Nine patients completed the SCS trial with > 50% pain relief. The pretrial NRS score was 7.8 ± 0.5 mm in treated patients vs. 6.5 ± 1.7 mm in control patients. At 3, 6 and 12 months, the NRS was reduced to 2.9 ± 0.7 mm, 1.7 ± 0.5 mm, and 2.9 ± 0.5 mm, respectively in treated patients. NRS was unchanged in the control patients (6.5 ± 1.9 mm). The ODI score prior to the SCS trial in treated patients was 53.1 ± 3.4% vs. 54.0 ± 20.5 in control patients. At 3, 6 and 12 months the ODI scores were 39.0 ± 8.0%, 38.7 ± 4.6%, and 41.1 ± 3.9%, respectively in the treated patients, and 48.5 ± 29.5 at 12 months in control patients. In 6 patients receiving opioids prior to the SCS trial, average consumption was reduced by 69% (P = 0.036) over 12 months of therapy as compared with a 54% increase in the control patients. SCS usage was stable over the 12-month study., Conclusions: The current study indicates that SCS may provide effective pain relief, improve disability, and reduce opioid usage in patients with discogenic pain., (© 2011 The Authors. Pain Practice © 2011 World Institute of Pain.)

Aims: We studied the changes in the incidence of lower limb amputation (LLA) in Andalusia from 1998 to 2006 in the population with and without diabetes., Methods: We undertook a retrospective study of all LLA performed in Andalusia in people aged 30 years old, with or without diabetes, between 1 January 1998 and 31 December 2006. We obtained the crude and standardized incidence rates by year, and sex for three periods: 1998-2000, 2001-2003 and 2004-2006 and calculated the RR of requiring LLA in patients with diabetes. To test for time trend, Poisson regression models were fitted., Results: A total of 16,210 LLA were carried out in Andalusia, 72.6% in patients with diabetes mellitus and 66.4% in men. In the population with diabetes the standardized incidence of all LLA was found to be 344.0 per 100,000 (95% CI, 315.4-372.4) in 2004-2006. There was an estimated incidence increase for all LLA by 14% and for minor LLA by 13.6% in 2004-2006. In people with diabetes the RR increased by 31.6% as compared to the first period., Conclusions: Despite the implementation of a care plan for patients with diabetes, the incidence of LLA has not fallen in Andalusia in recent years., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Cancer patients with bone metastases are at risk of a variety of skeletal events, including vertebral compression and pathologic fractures. Approximately 30% to 40% of patients with advanced lung cancer will develop bone metastases in the course of their disease, resulting in a significant negative impact on both morbidity and survival. Skeletal complications of bone metastases include pain, pathologic fractures, spinal cord compression, and hypercalcemia. The spine is the most frequent site of skeletal metastases. We present a 48-year-old female with intractable and incapacitating low back pain because of metastatic bone tumor in the left lateral side of S1 and S2 with left sacroiliac invasion. Imaging identified a metastatic invasion of the sacrum. Percutaneous sacroplasty, a safe and effective procedure for sacral-insufficient fractures, was performed under fluoroscopy guidance. However, the expected pain relief was not achieved. At 1 month, the patient remained invalided by severe back pain, which was localized to the left sacroiliac joint. In a second procedure, the sacroiliac joint was cemented. Pain relief was complete, immediate, and sustained until the patient's death related to the underlying oncologic disease. No complications were observed. Few reports exist about the treatment of sacral metastatic tumors with percutaneous sacroplasty. Further, no previous reports about sacroiliac joint cementation for joint stabilization have been found. In the present case, sacroiliac joint cementation successfully resolved residual pain that remained despite percutaneous sacroplasty treatment of the pathologic sacral fracture., (© 2011 The Authors. Pain Practice © 2011 World Institute of Pain.)

The perpetual pursuit of pain elimination has been constant throughout human history and pervades human cultures. In some ways it is as old as medicine itself. Cultures throughout history have practiced the art of pain management through remedies such as oral ingestion of herbs or techniques believed to have special properties. In fact, even Hippocrates wrote about the practice of trepanation, the cutting of holes in the body to release pain. Current therapies for management of pain include the pervasive utilization of opioids, which have an extensive history, spanning centuries. There is general agreement about the appropriateness of opioids for the treatment of acute and cancer pain, but the long-term use of these drugs for treatment of chronic non-malignant pain remains controversial. The pros and cons regarding these issues are beyond the scope of this review. Instead, the purpose of this review will be directed towards the pharmacology of commonly prescribed opioids in the treatment of various chronic pain syndromes. Opium, derived from the Greek word for "juice," is extracted from the latex sap of the opium poppy (Papaverum somniferum). The juice of the poppy is the source of some 20 different alkaloids of opium. These alkaloids of opioids can be divided into 2 chemical classes: phenanthrenes (morphine, codeine, and thebaine) and benzylisoquinolines (agents that do not interact with opioid receptors).

Carpal tunnel syndrome (CTS) is a common disorder. In the majority of cases, patients with CTS can be diagnosed by means of appropriate history taking. Nerve conduction examination of the nervus medianus is the most important additional diagnostic test and is the best predictor of symptom severity and functional status in idiopathic CTS. Treatment option depends on the severity of the symptoms and the degree of functional daily limitations. If few limitations are present, splinting or corticosteroid injections are preferred. Surgical interventions are reserved for the more severe conditions resulting in significant disability.Interventional pain treatment such as pulsed radio frequency could be an addition to the future treatment options for CTS.

Background: Even though opioids have been used for pain for thousands of years, opioid therapy for chronic non-cancer pain is controversial due to concerns regarding the long-term effectiveness and safety, particularly the risk of tolerance, dependance, or abuse. While the debate continues, the use of chronic opioid therapy for chronic non-cancer pain has increased exponentially. Even though evidence is limited, multiple expert panels have concluded that chronic opioid therapy can be effective therapy for carefully selected and monitored patients with chronic non-cancer pain., Study Design: A systematic review of randomized trials of opioid management for chronic non-cancer pain., Objective: The objective of this systematic review is to evaluate the clinical efficacy of opioids in the treatment of chronic non-cancer pain., Methods: A comprehensive evaluation of the literature relating to opioids in chronic non-cancer pain was performed. The literature was evaluated according to Cochrane review criteria for randomized controlled trials (RCTs) and Jadad criteria. A literature search was conducted by using PubMed, EMBASE, Cochrane library, ECRI Institute Library, U.S. Food and Drug Administration (FDA) website, U.S. National Guideline Clearinghouse (NGC), Database of Abstracts of Reviews of Effectiveness (DARE), clinical trials, systematic reviews and cross references from systematic reviews. The level of evidence was classified as good, fair, or poor based on the quality of evidence developed by the United States Preventive Services Task Force (USPSTF) and used by other systematic reviews and guidelines., Outcome Measures: Pain relief was the primary outcome measure. Other outcome measures were functional improvement, withdrawals, and adverse effects., Results: Based on the USPSTF criteria, the indicated level of evidence was fair for Tramadol in managing osteoarthritis. For all the drugs assessed, including Tramadol, for all other conditions, the evidence was poor based on either weak positive evidence, indeterminate evidence, or negative evidence., Limitations: A paucity of literature, specifically with follow-up beyond 12 weeks for all types of opioids with controlled trials for various chronic non-cancer pain conditions., Conclusions: This systematic review illustrated fair evidence for Tramadol in managing osteoarthritis with poor evidence for all other drugs and conditions. Thus, recommendations must be based on non-randomized studies.

Background: Opioids have been utilized for thousands of years to treat pain and their use continues to escalate. It is estimated that 90% of the patients who present to pain centers and receive treatment in such facilities are on opioids. However, in contrast to increasing opioid use and the lack of evidence supporting long-term effectiveness in chronic non-cancer pain, is the escalating misuse of prescription opioids, including abuse and diversion. There is also uncertainty about the incidence and clinical salience of multiple, poorly characterized adverse drug events, including endocrine dysfunction, immunosuppression, infectious disease, opioid-induced hyperalgesia, overdoses, deaths, and psychosocial and economic implications., Study Design: A comprehensive review of the literature., Objective: The objective of this comprehensive review is to evaluate the clinical effectiveness and safety of chronic opioid therapy in chronic non-cancer pain., Methods: A comprehensive review of the literature relating to chronic opioid therapy in chronic non-cancer pain. The literature was collected from various electronic and other sources. The literature that was evaluated included randomized trials, observational studies, case reports, systematic reviews, and guidelines., Outcome Measures: Pain relief was the primary outcome measure. The secondary outcome measures were functional improvement and adverse effects. Short-term effectiveness was considered to be less than 6 months; long-term effectiveness was considered to be at least one year., Results: Given the complexity and widespread nature of opioid therapy, there is a paucity of qualitative and/or quantitative literature. The available evidence is weak for pain relief combined with improvement in functional status. Only one drug, tramadol, is effective for pain relief and improvement of functional status., Limitations: This is a narrative review without application of methodologic quality assessment criteria. Even so, a paucity of literature exists concerning both controlled and observational literature for multiple drugs and multiple conditions of chronic non-cancer pain., Conclusions: This comprehensive review illustrates the lack of literature on long-term opioid therapy; thus, opioid therapy should be provided with great restraint and caution, based on the weak evidence available.

Chronic noncancer pain is highly prevalent with associated negative effects on function and quality of life of the individuals involved. Opioids have been shown to decrease pain and improve function in some patients with chronic noncancer pain, but they are not always effective and are associated with multiple complications, including drug misuse, abuse and diversion. Furthermore, the effectiveness of opioids in decreasing pain and improving function has not been proven conclusively, resulting in continued uncertainty about long-term benefits of opioids for chronic noncancer pain. Ideally, in modern medicine, clinical decisions are made based on information derived from high quality evidence. Since no such evidence exists for chronic opioid therapy in chronic noncancer pain, this review describes various aspects of opioid therapy in chronic noncancer pain, including adherence monitoring, along with a ten-step process outlining the principles of effective and safe opioid use.