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Neuropathic pain is a debilitating chronic pain condition, and its treatment remains a clinical challenge. Curcumin, a naturally occurring phenolic compound, possesses diverse biological and pharmacological effects but has not yet been approved as a drug due to its low bioavailability. In order to overcome this limitation, we synthesized a potential ester prodrug of curcumin, curcumin diethyl diglutarate (CurDDG). In this study, we evaluated the pharmacological advantages of CurDDG over curcumin in a mouse model of chronic constriction injury (CCI), and the anti-inflammatory effect of CurDDG in LPS-induced RAW 264.7 macrophage cells was accessed to clarify the underline mechanism. Mice were treated with various oral doses of curcumin (25, 50, 100 and 200 mg/kg/day, daily for 14 days) or equimolar doses of CurDDG. CurDDG at all doses tested significantly attenuated CCI-induced thermal hyperalgesia and mechanical allodynia compared with the CCI-control group. CurDDG at 25, 50 and 100 mg/kg demonstrated significantly greater efficacy on both mechanical and thermal hypersensitivities compared to that of curcumin. The effect of CurDDG correlated well with the inhibition of TNF-α and IL-6 levels in both the sciatic nerve and the spinal cord, as compared to its respective control groups. Similarly, in the in vitro study, CurDDG significantly reduced the LPS-induced expression of TNF-α and IL-6. Moreover, CurDDG significantly decreased COX-2 and iNOS levels and attenuated p38, JNK, and ERK1/2 phosphorylation as compared to the curcumin-treated cells. Altogether, this study demonstrated the improved pharmacological effects of curcumin by its diglutarate conjugate, CurDDG., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The use of morphine is controversial due to the incidence of rewarding behavior, respiratory depression, and tolerance, leading to increased drug dose requirements, advancing to morphine addiction. To overcome these barriers, strategies have been taken to combine morphine with other analgesics. Neuropeptide B23 and neuropeptide W23 (NPB23 and NPW23) are commonly used to relieve inflammatory pain and neuropathic pain. As NPB23 and NPW23 system shares similar anatomical basis with opioid system at least in the spinal cord we hypothesized that NPB23 or NPW23 and morphine may synergistically relieve inflammatory pain and neuropathic pain. To test this hypothesis, we demonstrated that μ opioid receptor and NPBW1 receptor (receptor of NPB23 and NPW23) are colocalized in the superficial dorsal horn of the spinal cord. Secondly, co-administration of morphine witheitherNPB23 or NPW23 synergistically attenuated inflammatory and neuropathic pain. Furthermore, either NPB23 or NPW23 significantly reduced morphine-induced conditioned place preference (CPP) and constipation. We also found that phosphorylation of extracellular-regulated protein kinase (ERK1/2) following morphine was profoundly potentiated by the application of NPB23 or NPW23. Hence, combination of morphine with either NPB23 or NPW23 reduced dose of morphine required for pain relief in inflammatory and neuropathic pain, while effectively prevented some side-effects of morphine., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ethnopharmacology Relevance: Escin is a natural mixture of triterpene saponins extracted from the seeds of Aesculus wilsonii Rehd. And has been reported to possess the therapeutic effects against neuropathic pain (NP). However, the underlying mechanisms remain unclear., Aim of the Study: The present study aimed to investigate the therapeutic effects and explore the underlying mechanisms of escin on rats of NP induced by chronic constriction injury (CCI) of sciatic nerve., Materials and Methods: Rats were treated with escin (7, 14, and 28 mg/kg, i. g.) daily from the third day after the surgery (day 0) for consecutive 14 days. Regular behavior and thermal threshold were measured on days 0, 3, 5, 7, 10 and 14. Investigations into mechanisms involved measurement of inflammatory factors and biochemical factors in dorsal root ganglion (DRG). Inflammatory pain responses and nerve injuries were induced by the CCI model. Tonic pain model and acute inflammatory model induced by formalin or carrageenan were established to evaluated the pharmacological effects of escin on acute inflammatory pain. Corresponding behaviors were monitored and relevant gene expression such as c-fos, mu opioid receptor (MOR) and KCNK1 were detected by qRT-PCR. Investigate the neuroprotective effects of escin on PC12 cell injury induced by lipopolysaccharide (LPS). Cell morphology was observed under inverted microscope and neuroprotective effect of escin on cell activity was assessed by MTT assay., Results: Escin could widen thermal threshold, downregulate the concentration of inflammatory factors like tumor necrosis factor (TNF)-α and interleukin (IL)-1β, suppress the gene expression of toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB), decrease the level of glial fibrillary acidic protein (GFAP) and nerve growth factor (NGF) remarkably. In addition, escin significantly lowered the duration of licking, numbers of flinches and increase in paw edema, showing great therapeutic effects on inflammatory pain responses. Moreover, the activity of injured PC12 cells was significantly improved after escin administrated., Conclusion: Escin exerted the ameliorative effects on NP induced by CCI which may be related to downregulating the release of pro-inflammatory cytokines, suppressing TLR-4/NF-κB signal pathway, thereafter decreasing the level of GFAP and NGF., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Researches have shown that calcitonin gene-related peptide (CGRP) plays a pivotal role in pain modulation. Nociceptive information from the periphery is relayed from parabrachial nucleus (PBN) to brain regions implicated involved in pain. This study investigated the effects and mechanisms of CGRP and CGRP receptors in pain regulation in the PBN of naive and neuropathic pain rats. Chronic sciatic nerve ligation was used to model neuropathic pain, CGRP and CGRP 8-37 were injected into the PBN of the rats, and calcitonin receptor-like receptor (CLR), a main structure of CGRP receptor, was knocked down by lentivirus-coated CLR siRNA. The hot plate test (HPT) and the Randall Selitto Test (RST) was used to determine the latency of the rat hindpaw response. The expression of CLR was detected with RT-PCR and western blotting. We found that intra-PBN injecting of CGRP induced an obvious anti-nociceptive effect in naive and neuropathic pain rats in a dose-dependent manner, the CGRP-induced antinociception was significantly reduced after injection of CGRP 8-37, Moreover, the mRNA and protein levels of CLR, in PBN decreased significantly and the antinociception CGRP-induced was also significantly lower in neuropathic pain rats than that in naive rats. Knockdown CLR in PBN decreased the expression of CLR and the antinociception induced by CGRP was observably decreased. Our results demonstrate that CGRP induced antinociception in PBN of naive or neuropathic pain rats, CGRP receptor mediates this effect. Neuropathic pain induced decreases in the expression of CGRP receptor, as well as in CGRP-induced antinociception in PBN., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: It is possible to observe the in-vivo movements of nerves using real-time ultrasound. In this study, we aimed to visualize the movements of the sciatic nerve as a guide to identify the sciatic nerve to distinguish from surrounding tissue., Methods: This trial was a prospective, cross-over comparative study. We included 25 healthy volunteers in this study. The movements of the sciatic nerve were visualized in the transverse view at popliteal and midthigh levels using ultrasonography. Anterior-posterior movements were assessed by measuring skin-to-nerve distance. The distances were measured during maximum ankle dorsiflexion, maximum plantar flexion and neutral position and compared with each other. We also evaluated the quality of dynamic (real-time) rotation/lateral movements of the sciatic nerve by assigning a subjective observer score., Results: The movement of sciatic nerve was significant at popliteal region with active and passive ankle dorsiflexion which was 0.32 cm and 0.23 cm respectively (p=0.003). The movement of sciatic nerve was significant at midthigh region with active and passive ankle plantar flexion which was 0.11 cm and 0.01 cm respectively (p<0.001). Excellent rotation/lateral movement was observed in subjects at popliteal region and good rotation/lateral movement was observed at midthigh level., Conclusion: Sciatic nerve movement can be observed with ankle dorsiflexion and plantar flexion in the transverse plane at popliteal and midthigh locations under real time ultrasound. This preliminary study suggest that observing the movements of sciatic nerve is potentially valuable in clinical sciatic nerve blocks for facilitating the localization of the sciatic nerve.

Objective: Neuropathic pain caused by traumatic neuromas is an extremely intractable clinical problem. Disorderly scar tissue accumulation and irregular and immature axon regeneration around the injury site mainly contribute to traumatic painful neuroma formation. Therefore, successfully preventing traumatic painful neuroma formation requires the effective inhibition of irregular axon regeneration and disorderly accumulation of scar tissue. Considering that chondroitin sulfate proteoglycans (CSPGs) can act on the growth cone and effectively inhibit axon regeneration, the authors designed and manufactured a CSPG-gelatin blocker to regulate the CSPGs' spatial distribution artificially and applied it in a rat model after sciatic nerve neurectomy to evaluate its effects in preventing traumatic painful neuroma formation., Methods: Sixty female Sprague Dawley rats were randomly divided into three groups (positive group: no covering; blank group: covering with gelatin blocker; and CSPG group: covering with the CSPG-gelatin blocker). Pain-related factors were evaluated 2 and 8 weeks postoperatively (n = 30). Neuroma growth, autotomy behavior, and histological features of the neuromas were assessed 8 weeks postoperatively (n = 30)., Results: Eight weeks postoperatively, typical bulb-shaped neuromas did not form in the CSPG group, and autotomy behavior was obviously better in the CSPG group (p < 0.01) than in the other two groups. Also, in the CSPG group the regenerated axons showed a lower density and more regular and improved myelination (p < 0.01). Additionally, the distribution and density of collagenous fibers and the expression of α-smooth muscle actin were significantly lower in the CSPG group than in the positive group (p < 0.01). Regarding pain-related factors, c-fos, substance P, interleukin (IL)-17, and IL-1β levels were significantly lower in the CSPG group than those in the positive and blank groups 2 weeks postoperatively (p < 0.05), while substance P and IL-17 remained lower in the CSPG group 8 weeks postoperatively (p < 0.05)., Conclusions: The authors found that CSPGs loaded in a gelatin blocker can prevent traumatic neuroma formation and effectively relieve pain symptoms after sciatic nerve neurotomy by blocking irregular axon regeneration and disorderly collagenous fiber accumulation in the proximal nerve stump. These results indicate that covering the proximal nerve stump with CSPGs may be a new and promising strategy to prevent traumatic painful neuroma formation in the clinical setting.

Neuropathic pain caused by somatosensory nervous system dysfunction is a serious public health problem. Some long noncoding RNAs (lncRNAs) can participate in physiological processes involved in neuropathic pain. However, the effects of lncRNA DGCR5 in neuropathic pain have not been explored. Therefore, in our current study, we concentrated on the biological roles of DGCR5 in neuropathic pain. Here, it was observed that DGCR5 was significantly decreased in chronic sciatic nerve injury (CCI) rat models. DGCR5 overexpression was able to alleviate neuropathic pain development including mechanical and thermal hyperalgesia. In addition, the current understanding of miR-330-3p function in neuropathic pain remains largely incomplete. Here, we found that miR-330-3p was greatly increased in CCI rats and DGCR5 can modulate miR-330-3p expression negatively. Upregulation of DGCR5 repressed inflammation-correlated biomarkers including interleukin 6 (IL-6), tumor necrosis factor α, and IL-1β in CCI rats by sponging miR-330-3p. The negative correlation between DGCR5 and miR-330-3p was confirmed in our current study. Inhibition of miR-330-3p suppressed neuropathic pain progression by restraining neuroinflammation in vivo. In addition, PDCD4 was predicted as a downstream target of miR-330-3p. Furthermore, PDCD4 was significantly increased in CCI rats and DGCR5 regulated PDCD4 expression through sponging miR-330-3p in CCI rat models. Taken these together, it was implied that DGCR5/miR-330-3p/PDCD4 axis participated in neuropathic pain treatment., (© 2018 Wiley Periodicals, Inc.)

Context: Accumulating evidence has demonstrated that Toll-like receptors (TLRs), especially TLR4 localized on microglia/macrophages, may play a significant role in nociception., Objective: We examine the role of TLR4 in a neuropathic pain model. Using behavioural/biochemical methods, we examined the influence of TLR4 antagonist on levels of hypersensitivity and nociceptive factors whose contribution to neuropathy development has been confirmed., Materials and Methods: Behavioural (von Frey's/cold plate) tests were performed with Wistar male rats after intrathecal administration of a TLR4 antagonist (LPS-RS ULTRAPURE (LPS-RSU), 20 μG: lipopolysaccharide from Rhodobacter sphaeroides, InvivoGen, San Diego, CA) 16 H and 1 h before chronic constriction injury (cci) to the sciatic nerve and then daily for 7 d. three groups were used: an intact group and two cci-exposed groups that received vehicle or LPS-RSU. tissue [spinal cord/dorsal root ganglia (DRG)] for western blot analysis was collected on day 7., Results: The pharmacological blockade of TLR4 diminished mechanical (from ca. 40% to 16% that in the INTACT group) and thermal (from ca. 51% to 32% that in the INTACT group) hypersensitivity despite the enhanced activation of IBA-1-positive cells in DRG. Moreover, LPS-RSU changed the ratio between IL-18/IL-18BP and MMP-9/TIMP-1 in favour of the increase of antinociceptive factors IL-18BP (25%-spinal; 96%-DRG) and TIMP-1 (15%-spinal; 50%-DRG) and additionally led to an increased IL-6 (40%-spinal; 161%-DRG), which is known to have analgesic properties in neuropathy., Conclusions: Our results provide evidence that LPS-RSU influences pain through the expression of TLR4. TLR4 blockade has analgesic properties and restores the balance between nociceptive factors, which indicates its engagement in neuropathy development.

Many studies have reported that microRNAs participate in neuropathic pain development. Previously, miR-200b and miR-429 are reported to be involved in various diseases. In our current study, we focused on their roles in neuropathic pain and we found that miR-200b and miR-429 were significantly decreased in chronic constriction injury (CCI) rat spinal cords and isolated microglials. miR-200b and miR-429 overexpression were able to relieve neuropathic pain through modulating PWT and PWL in CCI rats. Meanwhile, we observed that both miR-200b and miR-429 upregulation could repress neuroinflammation via inhibiting inflammatory cytokines such as IL-6, IL-1β, and TNF-α in CCI rats. By carry out bioinformatics technology, Zinc finger E box binding protein-1 (ZEB1) was predicted as target of miR-200b, and miR-429 and dual-luciferase reporter assays confirmed the correlation between them. ZEB1 has been reported to regulate a lot of diseases. Here, we found that ZEB1 was greatly increased in CCI rats and miR-200b and miR-429 overexpression markedly suppressed ZEB1 mRNA expression in rat microglial cells. In addition, knockdown of ZEB1 can reduce neuropathic pain development and co-transfection of LV-anti-miR-200b/miR-429 reversed this phenomenon in vivo. Taken these together, our results suggested that miR-200b/miR-429 can serve as an important regulator of neuropathic pain development by targeting ZEB1., (© 2017 Wiley Periodicals, Inc.)

Background Percutaneous laser disc decompression (PLDD) for patients with lumbar disc herniation is believed to be cheaper than surgery. However, cost-effectiveness has never been studied. Materials and Methods A cost utility analysis was performed alongside a randomized controlled trial comparing PLDD and conventional surgery. Patients reported their quality of life using the EuroQol five dimensions questionnaire (EQ-5D), 36-item short form health survey (SF-36 and derived SF-6D) and a visual analogue scale (VAS). Using cost diaries patients reported health care use, non-health care use and hours of absenteeism from work. The 1-year societal costs were compared with 1-year quality adjusted life years (QALYs) based on the United States (US) EQ-5D. Sensitivity analyses were carried out on the use of different utility measures (Netherland (NL) EQ-5D, SF-6D, or VAS) and on the perspective (societal or healthcare). Results On the US EQ-5D, conventional surgery provided a non-significant gain in QALYs of 0.033 (95% confidence interval (CI) -0.026 to 0.093) in the first year. PLDD resulted in significantly lower healthcare costs (difference €1771, 95% CI €303 to €3238) and non-significantly lower societal costs (difference €2379, 95% CI -€2860 to €7618). For low values of the willingness to pay for a QALY, the probability of being cost-effective is in favor of PLDD. For higher values of the willingness to pay, between €30,000 and €70,000, conventional microdiscectomy becomes favorable. Conclusions From a healthcare perspective PLDD, followed by surgery when needed, results in significantly lower 1-year costs than conventional surgery. From a societal perspective PLDD appears to be an economically neutral innovation.

Background: Multiple causes outside the spine can mimic spinal back pain. Endometriosis is an important gynecologic disorder, which commonly affects the lower region of the female pelvis and less frequently the spine and soft tissues. The lumbosacral trunk is vulnerable to pressure from any abdominal mass originating from the uterus and the ovaries. Therefore symptoms of endometriosis include severe reoccurring pain in the pelvic area as well as lower back and abdominal pain., Case Description: We report on a 39-year-old gymnast with cyclic sciatica and back pain, whose initial presentation initially led to a spinal fusion at L4/5 and L5/S1, but that procedure did not change her symptoms. Her diagnosis of endometriosis was not made until 2 years after her spinal fusion. Ultimately, once diagnosed with endometriosis of the retroperitoneal spinal and neural elements, her back and leg pain responded completely to hormonal therapy and then to a hysterectomy and a bilateral salpingo-oophorectomy. Because her true diagnosis of endometriosis was unknown and she had some degenerative changes in her spine, she underwent a spinal fusion that would probably not have been done if the diagnosis of endometriosis had been suggested., Conclusions: It is critical for any clinician who deals with back pain to at least consider the diagnosis of endometriosis in female patients who have a history of pelvic pain. The diagnosis of endometriosis should be considered in candidate patients by asking whether there is a significant hormonal cyclic nature to the symptoms, to prevent such unnecessary surgical adventures., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Objective: The role of leisure-time physical activity in sciatica is uncertain. This study aimed to assess the association of leisure-time physical activity with lumbar radicular pain and sciatica., Databases and Data Treatment: Literature searches were conducted in PubMed, Embase, Web of Science, Scopus, Google Scholar and ResearchGate databases from 1964 through August 2015. A random-effects meta-analysis was performed, and heterogeneity and small-study bias were assessed., Results: Ten cohort (N = 82,024 participants), four case-control (N = 9350) and four cross-sectional (N = 10,046) studies qualified for meta-analysis. In comparison with no regular physical activity, high level of physical activity (≥4 times/week) was inversely associated with new onset of lumbar radicular pain or sciatica in a meta-analysis of prospective cohort studies [risk ratio (RR) = 0.88, 95% CI 0.78-0.99, I 2  = 0%, 7 studies, N = 78,065]. The association for moderate level of physical activity (1-3 times/week) was weaker (RR = 0.93, CI 0.82-1.05, I 2  = 0%, 6 studies, N = 69,049), and there was no association with physical activity for at least once/week (RR = 0.99, CI 0.86-1.13, 9 studies, N = 73,008). In contrast, a meta-analysis of cross-sectional studies showed a higher prevalence of lumbar radicular pain or sciatica in participants who exercised at least once/week [prevalence ratio (PR) = 1.29, CI 1.09-1.53, I 2  = 0%, 4 studies, N = 10,046], or 1-3 times/week (PR = 1.34, CI 1.02-1.77, I 2  = 0%, N = 7631) than among inactive participants. There was no evidence of small-study bias., Conclusions: This meta-analysis suggests that moderate to high level of leisure physical activity may have a moderate protective effect against development of lumbar radicular pain. However, a large reduction in risk (>30%) seems unlikely., What Does This Review Add: Leisure-time physical activity may reduce the risk of developing lumbar radicular pain., Competing Interests: The authors declare that they have no conflicts of interest., (© 2016 European Pain Federation - EFIC®.)

Background: Early surgical treatment for back and leg pain secondary to disc herniation has been associated with very good outcomes. However, there are conflicting data on the role of surgical treatment in case of prolonged radicular symptomatology., Purpose: We aimed to evaluate whether the duration of symptoms at presentation affects the subjective outcome., Study Design/setting: This is a retrospective review of prospectively collected data from a single surgeon including micro-discectomies and lateral recess decompressions in patients younger than 60 years old using patient medical notes, radiology imaging, operation notes, and Patient Reported Outcome Measures (PROMS) including Oswestry Disability Index (ODI), visual analogue scale for back pain and leg pain (VAS-BP and VAS-LP). The final follow-up was carried out through postal questionnaire or telephone consultation., Methods: Demographic information, duration of symptoms, type and incidence of complications, length of hospital stay, and follow-up were analyzed. Data were categorized into four subgroups: symptoms 0≥6 months, 6 months≥1 year, 1 year≥2 years, and >2 years. A clinically significant result was an average improvement of 2 or more points in the VAS and of 20% and over in the ODI. The level of statistical significance was <0.05%., Results: A total number of 107 patients who underwent 109 operations were included. The level of surgery was L5/S1 (50), L4/L5 (43), L3/L4 (3), L2/L3 (2), and two levels (11). The mean improvement was from 0 to ≤6 months (VAS-LP 5.21±2.81, VAS-BP 3.04±3.15, ODI 35.26±19.25), 6 months to ≤1 year (VAS-LP 4.73±2.61, VAS-BP 3.30±3.05, ODI 26.92±19.49), 1 year to ≤2 years (VAS-LP 3.78±3.68, VAS-BP 3.00±2.78, ODI 19.03±20.24), and >2 years (VAS-LP 4.77±3.61, VAS-BP 3.54±3.43, ODI 28.36±20.93). The length of hospital stay and complication rate was comparable between groups. Average follow-up was 15.69 months., Conclusions: Our study showed significant improvement in patients with symptoms beyond 1 as well as 2 years since onset, and surgery is a viable option in selected patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Mitochondria play an important role in many cellular and physiologic functions. Mitochondria are dynamic organelles, and their fusion and fission regulate cellular signaling, development, and mitochondrial homeostasis. The most common complaint of human immunodeficiency virus (HIV)-sensory neuropathy is pain on the soles in patients with HIV, but the exact molecular mechanisms of HIV neuropathic pain are not clear. In the present study, we investigated the role of mitochondrial dynamin-related protein 1 (Drp1, a GTPase that mediates mitochondrial fission) in the perineural HIV coat glycoprotein gp120-induced neuropathic pain state., Methods: Neuropathic pain was induced by the application of recombinant HIV-1 envelope protein gp120 into the sciatic nerve. Mechanical threshold was tested using von Frey filaments. The mechanical threshold response was assessed over time using the area under curves. Intrathecal administration of antisense oligodeoxynucleotide (ODN) against Drp1, mitochondrial division inhibitor-1 (mdivi-1), or phenyl-N-tert-butylnitrone (a reactive oxygen species scavenger) was given. The expression of spinal Drp1 was examined using western blots. The expression of mitochondrial superoxide in the spinal dorsal horn was examined using MitoSox imaging., Results: Intrathecal administration of either antisense ODN against Drp1 or mdivi-1 decreased mechanical allodynia (a sensation of pain evoked by nonpainful stimuli) in the gp120 model. Intrathecal ODN or mdivi-1 did not change basic mechanical threshold in sham surgery rats. Intrathecal Drp1 antisense ODN decreased the spinal expression of increased Drp1 protein induced by peripheral gp120 application. Intrathecal phenyl-N-tert-butylnitrone reduced mechanical allodynia. Furthermore, both intrathecal Drp1 antisense ODN and mdivi-1 reversed the upregulation of mitochondrial superoxide in the spinal dorsal horn in the gp120 neuropathic pain state., Conclusions: These data suggest that mitochondrial division plays a substantial role in the HIV gp120-related neuropathic pain state through mitochondrial reactive oxygen species and provides evidence for a novel approach to treating chronic pain in patients with HIV.

Aim: To identify differences between defense styles and mechanisms in sciatica patients with or without neuropathic pain and their relationship to quality of life., Study Design: The study included 37 sciatica patients with neuropathic pain (SNP), 36 sciatica patients without neuropathic pain and 38 healthy subjects. Pain severity was measured using the Visual Analogue Scale (VAS). Psychological condition was assessed using the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI). Defense mechanisms were assessed using a 40-item Defense Style Questionnaire (DSQ-40) and quality of life was assessed using Short Form-36 (SF-36)., Results: BDI and BAI scores were significantly higher in the SNP group (p < 0.001). Idealization and immature defense styles, as well as isolation, displacement and somatization were significantly higher in the SNP group (p < 0.05). SF-36 parameters also differed significantly between the groups, with controls having the best scores and the SNP group the worst. In linear regression analysis, acting out and BDI were found to affect the pain domain of the SF-36 (p < 0.001)., Conclusion: The acting out defensive style and BDI were independently associated with pain-related quality of life. In the SNP group, significant differences were found in the immature and neurotic styles of the defense mechanisms.

Background: Insulin therapy plays a critical role in managing type 1 diabetes mellitus, and exercise produces alterations in pain sensation. This experiment explored the effects of insulin therapy combined with treadmill training on diabetic neuropathic pain and on the expression of malondialdehyde (MDA) and cytokines., Methods: Rats were given 4 weeks of insulin (100 IU/kg) therapy and treadmill training (30-60 min/d of training at 20-25 m/min) each day beginning on day 3 after streptozotocin (65 mg/kg, IV) injection and continuing until day 27. Sensitivity to heat and mechanical stimuli and the expression of interleukin (IL)-10, IL-6, tumor necrosis factor-α, and MDA in the sciatic nerve were estimated., Results: We showed that 2 to 4 weeks of treadmill training, insulin treatment, or their combination increased both paw withdrawal thresholds and latencies compared with the same regimen in sedentary diabetic rats (all P < 0.0022). Treatment with insulin, but without treadmill training, had significant effects on glycemic control (P < 0.0001) and restored body weight (P < 0.0001) in the diabetic rats. The diabetic rats demonstrated the upregulation (all P < 0.009) of IL-6, MDA, and tumor necrosis factor-α in the sciatic nerve on days 14 and 28 after streptozotocin treatment, whereas in diabetic rats receiving insulin, treadmill training, or a combination (all P < 0.01), this upregulation was decreased. Insulin, treadmill training, or the combination increased IL-10 expression (all P < 0.0051) in all diabetic rats., Conclusions: Treadmill training combined with insulin therapy showed the best improvements in tactile allodynia and thermal hyperalgesia among our 3 treatment groups. The benefits of insulin intervention and treadmill training could be related to chronic inflammation (proinflammatory cytokines) and oxidative stress (MDA).

The iliolumbar artery (ILA) is a standard branch from the posterior trunk of the internal iliac artery. It is the only pelvic artery ascending from pelvic cavity. Current study comprises 171 cadavers dissection to assess the origin variability of ILA. The present study identified the incidence of the ILA origin variability in Caucasian population which also clarified the iliolumbar variability in males and females. The current study shows that the ILA arises from the common iliac artery in 2%, from the external iliac artery in 0.3% and from the internal iliac artery in 13.8% either from its dorsal or dorsomedial aspects in 1 and 12.8%, respectively. The common, external and internal iliac arteries are defined as a high (early) origin and occurred in 16.1%. The posterior trunk of the internal iliac artery is the most common origin of the ILA found to be in 77.9%. Occasionally, it also arose from the superior gluteal artery (0.7%) and the sciatic artery (0.3%). Furthermore, the ILA arises from the anterior trunk indirectly as from the inferior gluteal artery in 0.3%. The ILA arising from the superior or inferior gluteal artery or from the sciatic artery is defined as a low (delayed) origin and occurred in 1.3%. In contrast, the ILA was 4.7%. Consequently, variability of the ILA leads to vascular variability of the lumbosacral trunk of the sciatic nerve. Clinicians have to be aware of these variations to avoid unnecessary ligation to prevent sciatic neuropathy.

The mechanism of botulinum toxin type A (BTX-A) antinociceptive action in the central nervous system is little known. The potential interaction between BTX-A and GABAergic system has not been investigated previously. In the present study, we demonstrate prevention of BTX-A antinociceptive effect on formalin-induced inflammatory pain and partial sciatic nerve transection-induced mechanical allodynia by GABA-A antagonist bicuculline, thus suggesting association of the GABA-A receptors and antinociceptive action of BTX-A.

Various therapies are accessed by women who are looking to enhance the experience of pregnancy or to relieve pain from pregnancy-related ailments. This article gives an introduction to how osteopathy may help women presenting with pain. It includes an overview of a case study, in order that midwives can gain insight into how osteopathic medicine approaches and applies knowledge of anatomy and physiology to improve biomechanics that may have become sub optimal giving the symptom of pain. An underlying philosophy of structure governs function.

Trophic support and myelination of axons by Schwann cells in the PNS are essential for normal nerve function. Herein, we show that deletion of the LDL receptor-related protein-1 (LRP1) gene in Schwann cells (scLRP1(-/-)) induces abnormalities in axon myelination and in ensheathment of axons by nonmyelinating Schwann cells in Remak bundles. These anatomical changes in the PNS were associated with mechanical allodynia, even in the absence of nerve injury. In response to crush injury, sciatic nerves in scLRP1(-/-) mice showed accelerated degeneration and Schwann cell death. Remyelinated axons were evident 20 d after crush injury in control mice, yet were largely absent in scLRP1(-/-) mice. In the partial nerve ligation model, scLRP1(-/-) mice demonstrated significantly increased and sustained mechanical allodynia and loss of motor function. Evidence for central sensitization in pain processing included increased p38MAPK activation and activation of microglia in the spinal cord. These studies identify LRP1 as an essential mediator of normal Schwann cell-axonal interactions and as a pivotal regulator of the Schwann cell response to PNS injury in vivo. Mice in which LRP1 is deficient in Schwann cells represent a model for studying how abnormalities in Schwann cell physiology may facilitate and sustain chronic pain.

Pyrroloquinoline quinone PQQ is a naturally occurring redox cofactor that acts as an essential nutrient, antioxidant, and redox modulator. PQQ has been demonstrated to oxidize the redox modulatory site of N-methyl-d-aspartic acid (NMDA) receptors. Such agents are known to be neuroprotective in experimental stroke models. However, there is not report about the therapeutic effect of PQQ on neuropathic pain. We tested the effects of oral administration of PQQ on neuropathic pain of rats with chronic constriction injury (CCI) of the sciatic nerve. The repeated oral administration of PQQ (20 and 40mg/kg, once a day for 4 weeks, from day 1 after the injury) attenuated both thermal and mechanical hyperalgesia, and also attenuated the muscle atrophy. The anti-hyperalgesic activity of PQQ was associated with a significant reduction of pro-inflammatory mediators such as tumor necrosis factor alpha (TNF-α) and lipid peroxide malondialdehyde (MDA) levels. In the present investigation, PQQ is shown to have analgesic effect which was found in the first time, probably through reducing the release of pro-inflammatory mediator and inhibiting oxidative stress., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background and Purpose: Synovial cysts of the spine occur most frequently in the lumbosacral region. Methods of treatment vary, but in cases of chronic pain or neurological deficits surgical intervention is undertaken. The aim of this paper is to present indications, surgical technique and efficacy of surgical treatment in patients with synovial cyst of the spinal canal., Material and Methods: The retrospective analysis included 11 patients, aged from 47 to 72 years, treated at the Department of Neurosurgery and Neurotraumatology, Poznan University of Medical Sciences, between 2004 and 2009. The length of medical history ranged from 2 months to 6 years. Conservative treatment applied before surgery was not effective. Neurological examination revealed unilateral or bilateral sciatica, superficial sensory disturbance or lower limb paresis., Results: Synovial cysts were located mainly at the L4-L5 level (9 cases). Magnetic resonance imaging (MRI) of the spine was performed in all patients and showed the cystic lesion attached to the intervertebral joint. Surgical treatment consisted of a unilateral fenestration using microsurgical techniques in most cases. Back pain relief was observed in 9 cases. In 10 patients, symptoms of sciatica disappeared. Neurological deficits disappeared in 5 patients., Conclusions: Surgical treatment of spinal synovial cysts is safe, effective and ensures a long-lasting effect. Surgical treatment is indicated in patients in whom the clinical symptoms correlate with the presence of synovial cyst in imaging studies and do not resolve after conservative treatment.

Object: Advocates of minimally invasive discectomy (MID) have promoted this operation as an alternative to open discectomy (OD), arguing that there may be less injury to the paraspinal muscles, decreased postoperative pain, and a faster recovery time. However, a recently published large randomized controlled trial (RCT) comparing these approaches reported inferior relief of leg pain in patients undergoing MID. The authors conducted a meta-analysis to evaluate complications and improvement in leg pain in patients with radiculopathy enrolled in RCTs comparing OD to MID., Methods: The authors performed a literature search using Medline and EMBASE of studies indexed between January 1990 and January 2011. Predetermined RCT eligibility included the usage of tubular retractors during MID, a minimum follow-up duration of 1 year, and quantification of pain with the visual analog scale (VAS). Trials that only evaluated patients with recurrent disc herniation were excluded. Data on operative parameters, complications, and VAS scores of leg pain were extracted by 2 investigators. A meta-analysis was performed assuming random effects to determine the difference in mean change for continuous outcomes and the risk ratio for binary outcomes., Results: Six trials comprising 837 patients (of whom 388 were randomized to MID and 449 were randomized to OD) were included. The mean operative time was 49 minutes during MID and 44 minutes during OD; this difference was not statistically significant. Incidental durotomies occurred significantly more frequently during MID (5.67% compared with 2.90% for OD; RR 2.05, 95% CI 1.05-3.98). Intraoperative complications (incidental durotomies and nerve root injuries) were also significantly more common in patients undergoing MID (RR 2.01, 95% CI 1.07-3.77). The mean preoperative VAS score for leg pain was 6.9 in patients randomized to MID and 7.2 in those randomized to OD. With long-term follow-up (1-2 years postoperatively), the mean VAS score improved to 1.6 in both the MID and OD cohorts. There was no significant difference in relief of leg pain between the 2 approaches with either short-term follow-up (2-3 months postoperatively, 0.81 points on the VAS, 95% CI -4.71 to 6.32) or long-term follow-up (2.64 on the VAS, 95% CI -2.15 to 7.43). Reoperation for recurrent herniation was more common in patients randomized to the MID group (8.50% compared with 5.35% in patients randomized to the OD group), but this difference was not statistically significant (RR 1.56, 95% CI 0.92-2.66). Total complications did not differ significantly between the operations (RR 1.50, 95% CI 0.97-2.33)., Conclusions: The current evidence suggests that both OD and MID lead to a substantial and equivalent long-term improvement in leg pain. Adequate decompression, regardless of the operative approach used, may be the primary determinant of pain relief-the major complaint of many patients with radiculopathy. Incidental durotomies occurred significantly more frequently during MID, but total complications did not differ between the techniques.

Background: The use of opioids for pain management is often associated with nausea and vomiting. Although conventional antipsychotics are often used to counter emesis, they can be associated with extrapyramidal symptoms. However, chronic pain can induce sleep disturbance. The authors investigated the effects of the atypical antipsychotic olanzapine on morphine-induced emesis and the sleep dysregulation associated with chronic pain., Methods: A receptor binding assay was performed using mouse whole brain tissue. The emetic response in ferrets was evaluated by counting retching and vomiting behaviors. Catalepsy in mice was evaluated by placing both of their forepaws over a horizontal bar. Released dopamine was measured by an in vivo microdialysis study. Sleep disturbance in mice in a neuropathic pain-like state was assayed by electroencephalogram and electromyogram recordings., Results: Olanzapine showed high affinity for muscarinic M1 receptor in brain tissue. Olanzapine decreased morphine-induced nausea and vomiting in a dose-dependent manner. However, olanzapine at a dose that had an antiemetic effect (0.03 mg/kg) did not induce catalepsy or hyperglycemia. In addition, olanzapine at this dose had no effect on the morphine-induced release of dopamine or inhibition of gastrointestinal transit. Finally, olanzapine inhibited thermal hyperalgesia and completely alleviated the sleep disturbance induced by sciatic nerve ligation., Conclusion: These findings suggest that olanzapine may be useful for the treatment of morphine-induced emesis and as an adjunct for the treatment of neuropathic pain associated with sleep disturbance.

Epidural steroid injection (ESI) has been used as a treatment for low back pain for over 50 years. In the last 10 to 15 years, there has been a significant increase in the use of ESIs for the treatment of low back pain and radicular pain without clear improvements in outcomes. Recent literature has focused on the use of ESIs as treatment for radicular pain associated with low back pain, with some studies showing benefit over control groups for limb symptoms. There is a lack of literature, however, to support the use of ESIs for the treatment of axial low back pain. The theoretical basis for their use, technical considerations, and the literature available for different approaches of access to the epidural space as pertaining to the treatment for low back pain without radiculopathy are reviewed., (Copyright © 2010. Published by Elsevier Inc.)

Background: The mitogen-activated protein kinase family plays an important role in several types of pain. However, the detailed role of phosphorylated extracellular signal-regulated kinase (pERK) in the region of injured peripheral nerve is poorly understood. In this study, we investigated whether pERK in injured sciatic nerve contributes to neuropathic pain induced by partial sciatic nerve ligation (PSL) in mice., Methods: Mice received PSL; pERK1/2 (p44/42) in sciatic nerve was measured by both Western blotting and immunohistochemistry. U0126 (an ERK kinase inhibitor) was injected twice, an intraneural injection (20 nmol/2 microL) 30 min before PSL, and a perineural injection (20 nmol/10 microL) on Day 1 after PSL. Thermal hyperalgesia and tactile allodynia induced by PSL were evaluated by the thermal paw withdrawal test and the von Frey test, respectively., Results: As measured by Western blotting, in sham-operated mice, the levels of pERK1/2 in sciatic nerve were constant and the same as those in naive mice across Days 1-14. In PSL-operated mice, a significant increase in pERK1/2 was observed on Day 1 after PSL and persisted until Day 3. As measured by immunohistochemistry, immunoreactivity of pERK1/2 in PSL-operated sciatic nerve was markedly increased in comparison with that in sham-operated sciatic nerve on Day 1 after PSL. In the sciatic nerve on Day 1 after PSL, as indicated by double immunostaining, the increased immunoreactivity of pERK1/2 was colocalized with glial fibrillary acidic protein (GFAP), a marker of Schwann cells, but not F4/80, a marker of macrophages. PSL-induced thermal hyperalgesia was significantly attenuated by treatment with U0126 on Days 3, 7, and 14 after PSL. The PSL-induced tactile allodynia was also significantly attenuated by treatment with U0126 on Days 7 and 14 after PSL., Conclusion: Activation of ERK in Schwann cells of the injured peripheral nervous system may play an important role in the development of neuropathic pain. Our results suggest that pERK itself and ERK-related mediators are potential therapeutic targets for the treatment of neuropathic pain.

This article presents a unique case of posttraumatic extrapelvic endometriosis presenting as a gluteal mass causing cyclic sciatica. A 38-year-old woman presented with an enlarging right buttock mass over the previous 6 years. She also had symptoms of radicular pain referred to the right leg and foot with sitting and daily activity. Four years prior to noticing the mass, she sustained a gunshot wound through the lower abdomen while 5 months pregnant. Excisional biopsy of the gluteal mass revealed endometrioma. Sciatica is a common and painful disorder that is believed to have an incidence of 40% in the adult population. Sciatica is most often due to intraspinal pathology affecting the lumbar nerve roots. There are many recognized extraspinal etiologies for sciatica in the literature including aneurysms, sciatic hernia, abcess, neoplasm, trochanteric wire, piriformis syndrome, ischial fracture, a posteriorly flexed uterus, and even an intrauterine device following uterine perforation. Similarly, endometriosis is a gynecologic condition that represents a significant health problem for women of reproductive age as it occurs in up to 50% of premenopausal women and 71% to 87% in women with chronic pelvic pain. Although rare, endometriosis has a well known ability to migrate outside of the abdominal cavity and proliferate ectopically under the control of systemic estrogen.

Clinical and experimental evidence suggests that glucocorticoids may be effective in the treatment of neuropathic pain, but their mechanism of action is unknown. We gave triamcinolone (3 mg/kg) to rats with an experimental post-traumatic painful peripheral neuropathy, chronic constriction injury (CCI), five days after nerve injury, when the abnormal pain syndrome is known to be present; and pain sensitivity was measured on postoperative days 7 - 14, a period during which symptoms are known to be at approximately peak severity. Additional CCI rats were treated similarly; and then they were sacrificed five days after the injection for an immunocytochemical analysis of endoneurial tumor necrosis factor-alpha (TNFalpha), macrophages, and mast cells in the sciatic nerve proximal to the site of injury. Vehicle-injected CCI rats demonstrated the expected neuropathic pain symptoms. Triamcinolone-treated CCI rats had a statistically significant reduction in the magnitude of heat-hyperalgesia and mechano-allodynia, but there was no effect on cold-allodynia or mechano-hyperalgesia. On the nerve-injured side of vehicle-injected rats, TNFalpha was present in Schwann cells and mast cells. On the nerve-injured side of triamcinolone-treated rats, there was a significant (71.5%) reduction in the number of TNFalpha-positive mast cells. Our results suggest that glucocorticoid therapy for neuropathic pain may work via the reduced expression of TNFalpha in endoneurial mast cells.

Background: In clinical practice, the analgesic effects of epidurally administered local anesthetics on chronic pain sometimes outlast the duration of drug action expected from their pharmacokinetics. To investigate the underlying mechanisms of this prolonged effect, we examined the effects of ropivacaine, a local anesthetic, on pain-related behavior in a rat model of neuropathic pain. We also analyzed changes in the expression of nerve growth factor (NGF), which is involved in plasticity of the nociceptive circuit after nerve injury., Methods: In a rat model of neuropathic pain produced by chronic constrictive injury (CCI) of the sciatic nerve, thermal hyperalgesia, and mechanical allodynia were observed from Day 3 after surgery. Ropivacaine or saline was administered through an epidural catheter once a day, every day, and from Days 7-13 after the CCI operation. NGF content was measured in the L4 dorsal root ganglion, the hindpaw skin, the L4/5 dorsal spinal cord, and the sciatic nerve, using enzyme immunoassay., Results: The latency to withdrawal from thermal stimuli on the ipsilateral paw pads of CCI rats was significantly increased 4 days after the beginning of ropivacaine treatment, and thermal hyperalgesia was almost fully relieved. Similarly, mechanical allodynia was partially reduced after ropivacaine treatment. NGF content was increased in the L4 dorsal root ganglion on the ipsilateral, but not the contralateral, side, in CCI rats treated with ropivacaine., Conclusion: Repetitive administration of ropivacaine into the epidural space in CCI rats exerts an analgesic effect, possibly by inducing a plastic change in the nociceptive circuit.

We assessed the pain-relieving efficacy of static magnetic fields produced by 200 Gauss (G) magnets compared with 50G magnets in a double-blind, randomized, two-phase crossover study in patients with chronic lumbar radicular pain. The surface field strengths of the magnets were 200 and 50G. Phase I included four random periods of two-week duration: two periods with 200G, one period with 50G, and one period of "no treatment." The magnets were positioned either vertically or horizontally in standard lumbosacral elastic corsets. Phase II consisted of two five-week periods with the most effective magnet from Phase I and its corresponding 50 or 200G device. The primary outcome was average daily leg pain score (0-10 scale) in each period of Phase II. Thirty-eight of 40 randomized patients completed Phase I, and 28 of 31 Phase II participants completed the study. In Phase I, pain scores did not differ significantly between 200 and 50G magnets. Phase II average leg pain scores tended to be lower with 200 vs. 50G magnets (3.2+/-2.1 for 200G vs. 3.9+/-2.2 for 50G magnets [P=0.08]) after excluding one unblinded patient. The relative treatment effect of the 200G magnets appeared to increase throughout the five-week period. Although these data cannot rule out a chance effect, the positive trends suggest that larger, longer-duration, sham-controlled trials with 200G magnets be considered in patients with chronic lumbar radicular pain.

Background Context: There is limited information describing the correlation between the initial quantitative measurements on magnetic resonance imaging (MRI) scans of disc herniation area, canal cross-section areas, percent canal compromise, and disc herniation location to the need for surgery., Purpose: Our aim is to determine if the size of disc herniation area, canal cross-section area, percent canal compromise, and disc herniation location taken from MRI images of patients with symptomatic single-level lumbar herniated intervertebral discs upon initial presentation to a spine surgeon, were predictive of the need for surgical treatment., Study Design/setting: This is a retrospective case matched study of patient MRI images in the senior author's private practice., Patient Sample: From a pool of 332 patients with sciatica caused by lumbar intervertebral disc herniations at our institution, 65 patients had surgery, of which MRI images were available and analyzed on 44 patients. Forty-four additional patients were randomly selected from the remaining 267 original group as nonoperative controls., Methods: The axial MRI image showing the largest canal compromise by the herniated disc was selected for measurements. Using T1- and T2-weighted images, the areas of interest were digitally scanned at high resolution. The canal area and disc herniation area measurement were calculated from the total number of pixels per cross-sectional area, multiplied by a scan correction factor, mm(2) /pixel. Disc herniation locations were classified into either central or paracentral. The percent canal compromise was obtained by disc herniation area divided by canal cross-section area and multiplied by 100., Results: The surgical group's overall mean herniated disc area was 219.6 square millimeter (mm(2)), 179.8 at L4-5, and 267.4 at L5-S1. The nonoperative group's overall mean herniated disc area was 178.4 mm(2), 135.1 at L2-3, 160.3 at L4-5, and 207.4 at L5-S1. The surgical group's overall mean canal cross-sectional area was 471.8 mm(2), 418.6 at L4-5, and 535.6 at L5-S1. The nonoperative group's overall mean canal cross-sectional area was 541.3 mm(2), 518.1 at L2-3, 446.8 at L4-5, and 669.9 at L5-S1. The overall percent canal compromise ratio in the surgery group was 46.7%, 44.1% at L4-5, and 49.8% at L5-S1. The overall percent canal compromise in the nonoperative group was 34.2%, 34.1% at L2-3, 36.1% at L4-5, and 31.8% at L5-S1. The percent canal compromise in central herniations at L4-5 level was 53.0% in the surgical group, and 32.8% in the nonoperative group; at the L5-S1 level surgical group percent canal compromise was 64.1% and in the nonoperative group canal compromise was 27%. L4-L5 level paracentral herniations canal compromise was 36.7% in the surgical group compared with 42.5% canal compromise in the nonoperative group. At the L5-S1 level the canal compromise was 45% in the surgical group and 34.8% in the nonoperative group., Conclusions: Our findings show a trend for patients treated with surgery to have larger disc herniation areas and smaller canal cross-section areas, corresponding to larger percent canal compromise than the nonoperative group. Centrally located herniations followed this trend closely at all levels studied. However, the paracentral herniation at the L4-5 level does not follow this trend, possibly because paracentral disc herniation clinical course is determined more by herniation location rather than the overall herniation size.

As reported by previous literature, the prevalence of musculoskeletal disorders is high in population of local police officers, due to several risk factors, including awkward posture, jolt/vibrations and stress. The results of our study reveal that the most common musculoskeletal symptoms among local police officers are cervicobrachial pain, low back pain and sciatica. Low-back pain is associated with tasks exposing to awkward posture of the spine (traffic policemen and policemen involved in office-based duties); cervical and upper extremity disorders are related to the exposure to vibrations and to the upper limb posture held by motorcycle police. Among postural parameters, anterior scapular plane, flat back and Barre's vertical resulted possible predictive tests of adaptation of the postural system to the symptom pain in subjects with low back pain. In conclusion, it is necessary to adopt organizational, protective and preventive measures in order to occupational health of local police officers. They include: decrease of time periods during which an awkward posture is held, breaks between duties, prescription of ergonomic shoes, use of low-weight and low-volume duty-packs, and planning of periodical osteopathic check-ups as part of the health program, aimed to uncover initial postural alterations related to musculoskeletal disorders.

Despite many decades of drug development, effective therapies for neuropathic pain remain elusive. The recent recognition of spinal cord glia and glial pro-inflammatory cytokines as important contributors to neuropathic pain suggests an alternative therapeutic strategy; that is, targeting glial activation or its downstream consequences. While several glial-selective drugs have been successful in controlling neuropathic pain in animal models, none are optimal for human use. Thus the aim of the present studies was to explore a novel approach for controlling neuropathic pain. Here, an adeno-associated viral (serotype II; AAV2) vector was created that encodes the anti-inflammatory cytokine, interleukin-10 (IL-10). This anti-inflammatory cytokine is known to suppress the production of pro-inflammatory cytokines. Upon intrathecal administration, this novel AAV2-IL-10 vector was successful in transiently preventing and reversing neuropathic pain. Intrathecal administration of an AAV2 vector encoding beta-galactosidase revealed that AAV2 preferentially infects meningeal cells surrounding the CSF space. Taken together, these data provide initial support that intrathecal gene therapy to drive the production of IL-10 may prove to be an efficacious treatment for neuropathic pain.

Minimally invasive techniques for the treatment of degenerative pathology of the spine have come to be preferred by surgeons since the destructive effect on bony structures is eliminated and scar formation is dramatically reduced. A critical review of the pathogenetic mechanisms for low back pain and sciatalgia has recently yielded that mechanical compression is one but non essential component of the matter. The importance of chemical irritative processes is stressed. Coblation nucleoplasty is one of these minimally invasive techniques. It provokes ablation of the nucleus of the disk by a controlled thermal effect produced by radiofrequency. By this procedure one to two ml of tissue are colliquated in a few minutes. From February 2001 to May 2003 we treated 1390 patients for of lumbosciatalgic pain caused by disc pathology. The alteration consisted of disc bulging or contained disc herniation. Exclusion criteria as provided by the protocol of the multicentric study conceived by Conor O'Neill have been respected. This technique has been conceived in order to obtain progressive results in cases of contained disc herniation which has scanty natural tendency to shrinkage, as demonstrated by several studies on the natural history of evolution of this pathology. Contained disc herniation is a pathology most difficult to manage by conservative procedures, physiotherapy and drugs, but we all agree that open surgery should be avoided. By this minimally invasive procedure the patient will not be compelled to abandon physiotherapy and his normal daily activities for more than a few days.

Aim of this study was to assess the therapeutic outcome of CT-guided periganglionic infiltration of oxygen-ozone and injection of the gas mixture into the lysis points in patients with first grade spondylolisthesis and spondylolysis. We selected 18 patients presenting with low back pain and sciatica resistant to physical and medical management with a radiological diagnosis of spondylolisthesis and spondylolysis subsequently confirmed on CT scan. Following CT-guided bilateral periganglionic O2-O3 infiltration and injection into the lysis points, 15 patients (83.3%) obtained a complete remission of pain. None of the patients reported pain recurrence at clinical follow-up visits one, three and six months after treatment. Oxygen-ozone therapy administered in this way is even more effective than CT-guided periganglionic infiltration alone as it has an additional anti-inflammatory and analgesic effect on the nerve structures in the neural arch, namely Luschka's recurrent nerve.

Object: Although good surgical technique is effective in reducing postoperative epidural fibrosis, compression or tethering of the nerve root may cause recurrent radicular pain and physical impairment. The implantation of a bioresorbable gel on the dura may further decrease the amount of scar formation after surgery and thus improve the patient's ability to perform activities of daily living (ADL). This study is a 12-month evaluation of the safety and effectiveness of Oxiplex/SP Gel (FzioMed, Inc., San Luis Obispo, CA) in the reduction of pain and radiculopathy after lumbar discectomy., Methods: A pilot randomized single-blind multicenter clinical trial was conducted to evaluate the performance of Oxiplex/SP Gel in patients who underwent surgery for unilateral herniation of the lumbar disc at L4-5 or L5-S1. Eighteen patients with severe leg pain and lower-extremity weakness (11 women and seven men) were randomly assigned intraoperatively to receive the gel at the conclusion of surgery (treatment group) or to undergo surgery alone (control group). Self-assessment questionnaires (Lumbar Spine Outcomes Questionnaire) to assess pain, symptoms, and ADL were completed preoperatively and at scheduled postoperative intervals (30 days, 90 days, 6 months, and 12 months). The authors examined the spine and lower extremities of patients scheduled for discectomy to assess neurological function and pain. Treated patients received sufficient Oxiplex/SP Gel (1-3 ml) to coat the nerve root and fill the epidural space. Postoperative clinical evaluations were performed at 30 and 90 days. Patients completed the self-assessment questionnaires at baseline and were contacted by telephone or mail for the completion of the postoperative self-assessment questionnaires. Surgical procedures were well tolerated; no device-related adverse events and no clinically significant laboratory results were reported. The 11 patients with severe leg pain and lower-extremity weakness who were treated with Oxiplex/SP Gel had a reduction in those symptoms at 30 days, 90 days, 6 months, and 12 months after discectomy, compared with the seven control patients who underwent surgery only., Conclusions: Oxiplex/SP Gel was easy to use and safe in patients who underwent unilateral discectomy. A greater benefit in clinical outcome measures was seen over the 12-month follow-up period in gel-treated patients.

Study Design: An economic evaluation was conducted alongside a randomized controlled trial., Summary of Background Data: Little is known about the effectiveness of cognitive-behavioral treatment options for patients following lumbar disc surgery. If the knowledge available was supported by an economic evaluation, the information could then be used to make recommendations for the implementation of cognitive-behavioral treatment in the routine of rehabilitation following lumbar disc surgery., Objective: To examine the cost-effectiveness of a behavioral-graded activity program, which is an operant treatment, compared to usual care as delivered by a physical therapist for patients following first-time lumbar disc surgery., Methods: For the economic evaluation, a societal viewpoint was applied. The primary outcome measures (measured at the 12-month follow-up) were global perceived effect and functional status. To evaluate the economic consequences of the treatments, direct health care and non-health care costs were considered, as well as indirect costs., Results: The clinical outcomes showed no relevant differences between behavioral-graded activity (n = 52) and UC (n = 53). Treatment costs were almost identical in the two intervention groups. The difference in direct health care costs was, although not statistically significant, 264 EURO [95% CI: -3-525] higher in behavioral-graded activity than in usual care per patient-year. It was mainly the excess cost of visiting the physiotherapist in the behavioral-graded activity group that accounted for this difference. The difference in direct non-health care costs, although not statistically significant, was 388 EURO [95% CI: -217; 992] lower in the usual care group due to unpaid help by friends or family. Consequently, although again not statistically significant, the total direct costs in behavioral-graded activity are 639 EURO [95% CI: -91; 1368] higher than in usual care. For the indirect costs, there was a statistically significant difference, behavioral-graded activity being more expensive. The sensitivity analysis showed that these results are fairly robust., Conclusions: This study concludes that there are no differences between the two treatment conditions on any of the clinical outcome measures but that behavioral-graded activity is associated with higher costs. Consequently, there is no reason for the implementation of behavioral-graded activity as the standard treatment for patients following lumbar disc surgery.

Chronic injuries of the locomotor apparatus represent the main cause of drop-out among top level gymnasts. The aim of the present paper was to verify whether the postural control, investigated by using an integrated approach and accordingly optimized, could be an effective tool for the secondary prevention of training-related disorders of the locomotor apparatus, in a cohort of 20 young female athletes practicing rythmic gymnastic at top level. After a preliminary medical consultation all the subjects underwent a static and dynamic baropodometric test, an ophtalmological and a dental screening. Then athletes were given prescriptions based upon the results of the above named examination. After 6 months, symptoms were completely disappeared in 80% and remarkably improved in 20%, and at baropodometric test, the contact duration as well as the contact surface, the max and mean contact pressure were significantly increased in all the athletes. Our data show that the proposed integrated approach is actually an effective tool for the secondary prevention of training related disorders of the locomotor apparatus.

During continuous culture of neural PC12 cells, we obtained a drug-hypersensitive PC12 mutant cell that showed high stimulation of neurite outgrowth by various drugs. When several Chinese medicines such as shu-jing-huo-xie-tang and Wu-Ling-San were provided to these PC12 mutant cells, the frequency of nerve growth factor (NGF)-induced neurite outgrowth increased approximately 30-fold compared to NGF alone. Neurite outgrowth induced by NGF in PC12 cells is accompanied by sustained activation of mitogen-activated protein kinase (MAPK); however, these Chinese medicines did not induce MAPK activity. The findings thus indicate that certain Chinese medicines may induce neurite outgrowth by a novel mechanism which is distinct from the NGF-activated pathway in PC12 mutant cells.

Study Design: An experimental study to clarify the effects of pentoxifylline, as an anti-tumor necrosis factor-alpha therapy on endoneurial fluid pressure in the dorsal root ganglion using an animal model of herniated nucleus pulposus., Objectives: To investigate the effects of anti-tumor necrosis factor-alpha therapy to nucleus pulposus-induced nerve root/dorsal root ganglion changes., Summary of Background Data: It has been reported experimentally that application of nucleus pulposus into epidural space induces morphologic and functional changes in the nerve roots and induces compartment syndrome in the dorsal root ganglia. Tumor necrosis factor-alpha has been considered a key pathogenic factor in the initiation and maintenance of neuropathic pain states., Methods: A total of 11 adult, female Sprague-Dawley rats had their left L5 nerve roots and associated dorsal root ganglions exposed. Autologous nucleus pulposus was applied to the L5 nerve root just proximal to the dorsal root ganglion. A piece of Spongel (Yamanouchi Pharmaceutical Co., Tokyo) containing 20 microL of 1000 microg/mL pentoxifylline was applied with the nucleus pulposus (NP+PTX group). In control animals nucleus pulposus was applied with a piece of Spongel containing 20 microL of physiologic saline solution in a similar fashion (NP+PS group). Endoneurial fluid pressure was recorded with a servo-null micropipette system using glass micropipettes with tip diameters of 4 microm. Endoneurial fluid pressure in the dorsal root ganglion was measured before and 3 hours after application of test substances. After measurement of endoneurial fluid pressure, the nerve root and dorsal root ganglion were processed for histology and evaluated by light microscope., Results: Values of endoneurial fluid pressure before application of test substances were as follows: 2.4 +/- 1.2 cm H2O in the NP+PS (control) group and 1.8 +/- 0.4 cm H2O in the NP+PTX group. There was no statistically significant difference between these two pretreatment measurements. However, values of endoneurial fluid pressure after application were as follows: 8.6 +/- 1.8 cm H2O in the NP+PS group and 2.9 +/- 0.8 cm H2O in the NP+PTX group. Values of endoneurial fluid pressure in the NP+PTX group were significantly lower compared with the NP+PS group. Histologic examination consistently showed only a slight degree of edema evident in the NP+PTX group compared with the NP+PS group., Conclusion: Pentoxifylline, an anti-tumor necrosis factor-alpha drug, prevented the dorsal root ganglion compartment syndrome caused by topical application of nucleus pulposus. Anti-inflammatory cytokine therapy may become an effective treatment of sciatica due to disc herniation.

The effect of vincristine (Vin, a fast axonal transport blocker) to prevent any alteration in the excitability of dorsal horn neurons, following peripheral nerve injury, was investigated on 31 rats: 20 with chronic constriction injury (CCI) of the sciatic nerve and 11 sham preparations. In 15 of the 20 CCI rats, a small piece of gelfoam soaked with Vin was applied to the sciatic nerve before ligation (Vin+); in the remaining 5 rats the nerve was ligated without Vin (Vin-). The 11 sham rats were 7 Vin+ and 4 Vin-. The dorsal horn neuronal activity was recorded after 2-3 postoperative (PO) weeks. In the CCI Vin- rats, the neurons showed increased spontaneous activity and hyperresponsiveness to noxious stimulus with prolonged afterdischarges, events considered to signal central neuron sensitization. In the CCI Vin+ rats, the neuronal spontaneous and stimulated activity values were significantly lower (p < 0.001) than in the CCI Vin- rats being comparable to normal values. In sham Vin+ and Vin- rats, the neuronal activities had normal values. Given the crucial role attributed to central neuron sensitization for the development of neuropathic pain, the possibility that vincristine, by blocking the axonal transport, exerts a preventive action on this syndrome is discussed.