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Acute pain after breast surgery decreases the quality of life of cancer survivors. Previous studies using a variety of definitions and methods report prevalence rates between 10% and 80%, which suggests the need for a comprehensive framework that can be used to guide assessment of acute pain and pain-related outcomes after breast surgery. A multidisciplinary task force with clinical and research expertise performed a focused review and synthesis and applied the 5 dimensional framework of the AAAPT (Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks [ACTTION], American Academy of Pain Medicine [AAPM], American Pain Society [APS] Pain Taxonomy) to acute pain after breast surgery. Application of the AAAPT taxonomy yielded the following: 1) Core Criteria: Location, timing, severity, and impact of breast surgery pain were defined; 2) Common Features: Character and expected trajectories were established in relevant surgical subgroups, and common pain assessment tools for acute breast surgery pain identified; 3) Modulating Factors: Biological, psychological, and social factors that modulate interindividual variability were delineated; 4) Impact/Functional Consequences: Domains of impact were outlined and defined; 5) Neurobiologic Mechanisms: Putative mechanisms were specified ranging from nerve injury, inflammation, peripheral and central sensitization, to affective and social processing of pain. PERSPECTIVE: The AAAPT provides a framework to define and guide improved assessment of acute pain after breast surgery, which will enhance generalizability of results across studies and facilitate meta-analyses and studies of interindividual variation, and underlying mechanism. It will allow researchers and clinicians to better compare between treatments, across institutions, and with other types of acute pain.

Randomized clinical trials have demonstrated the efficacy of opioid analgesics for the treatment of acute and chronic pain conditions, and for some patients, these medications may be the only effective treatment available. Unfortunately, opioid analgesics are also associated with major risks (eg, opioid use disorder) and adverse outcomes (eg, respiratory depression and falls). The risks and adverse outcomes associated with opioid analgesics have prompted efforts to reduce their use in the treatment of both acute and chronic pain. This article presents Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus recommendations for the design of opioid-sparing clinical trials. The recommendations presented in this article are based on the following definition of an opioid-sparing intervention: any intervention that (1) prevents the initiation of treatment with opioid analgesics, (2) decreases the duration of such treatment, (3) reduces the total dosages of opioids that are prescribed for or used by patients, or (4) reduces opioid-related adverse outcomes (without increasing opioid dosages), all without causing an unacceptable increase in pain. These recommendations are based on the results of a background review, presentations and discussions at an IMMPACT consensus meeting, and iterative drafts of this article modified to accommodate input from the co-authors. We discuss opioid sparing definitions, study objectives, outcome measures, the assessment of opioid-related adverse events, incorporation of adequate pain control in trial design, interpretation of research findings, and future research priorities to inform opioid-sparing trial methods. The considerations and recommendations presented in this article are meant to help guide the design, conduct, analysis, and interpretation of future trials.

Ian Kudel,1 Markay Hopps,2 Joseph C Cappelleri,3 Alesia Sadosky,2 Kristen King-Concialdi,1 Ryan Liebert,1 Bruce Parsons,2 Patrick Hlavacek,2 Andrea H Alexander,2 Marco D DiBonaventura,4 John D Markman,5 John T Farrar,6 Brett R Stacey7 1Health Outcomes Practice, Kantar Health, New York, NY, USA; 2Pfizer Inc, New York, NY, USA; 3Pfizer Inc, Groton, CT, USA; 4Pfizer Inc, New York, NY, USA; 5University of Rochester Medical Center School of Medicine and Dentistry, Rochester, NY, USA; 6Department of Biostatistics and Epidemiology University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; 7UW Center for Pain Relief, University of Washington, Seattle, WA, USA Background: The aim of this study was to identify the clinical characteristics, treatment usage, and health outcomes of US adults diagnosed with neuropathic pain (NeP) by experienced physicians. Methods: Adults with scores exceeding the threshold for probable NeP (painDETECT ≥19) and diagnosed with NeP by a qualified physician completed a questionnaire that included comorbid conditions, pain symptoms and experiences, medication use, health status (3-level EuroQol 5 Dimensions (EQ-5D-3L]: health utilities index and visual analog scale), pain severity and interference with functioning (Brief Pain Inventory), and work and activity impairment (Work Productivity and Activity Impairment questionnaire). Descriptive analyses were performed for each NeP subtype. Results: Participants (n=295) were predominantly female (64.4%), middle-aged (53.9%), and white (51.5%). Chronic low back pain was the most frequently diagnosed major NeP syndrome (n=166), followed by diabetic peripheral neuropathy (n=58), post-trauma neuropathy (n=47), post-surgical neuropathy (n=28), and central NeP (n=23). An additional 45 participants were diagnosed, but did not meet the criteria for the aforementioned subtypes. Participants could be diagnosed with multiple subtypes. Across each NeP subtype, patients reported high rates of comorbid disease, including arthritis (range: 39.1%–64.3%) and high blood pressure (range: 26.1%–69.0%), as well as symptomology that included numbness (range: 68.1%–91.4%) and changes in muscular strength (range: 24.1%–65.2%). The majority of patients reported back pain (range: 77.8%–95.7%) and arthritis/joint pain (range: 68.1%–78.6%). The most commonly reported types of NeP pain medication were non-steroidal anti-inflammatory drugs (range: 43.1%–70.2%), weak opioids (range: 22.2%–39.3%), and strong opioids (range: 8.7%–28.6%). All six NeP groups generally reported similar levels of dysfunction on all self-report measures. The most notable finding was that the EuroQol-5D-3L health utilities index scores for each of the six groups were lower than the US norms by a clinically important amount. Conclusion: These exploratory findings indicate that patients with NeP across different etiologies are medically complex and experience impaired function across multiple domains. Keywords: activity impairment, functional status, health-related quality of life, neuropathic pain, pain medication use, physician diagnosis, work impairment

Objective With the increasing societal awareness of the prevalence and impact of acute pain, there is a need to develop an acute pain classification system that both reflects contemporary mechanistic insights and helps guide future research and treatment. Existing classifications of acute pain conditions are limiting, with a predominant focus on the sensory experience (e.g., pain intensity) and pharmacologic consumption. Consequently, there is a need to more broadly characterize and classify the multidimensional experience of acute pain. Setting Consensus report following expert panel involving the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), American Pain Society (APS), and American Academy of Pain Medicine (AAPM). Methods As a complement to a taxonomy recently developed for chronic pain, the ACTTION public-private partnership with the US Food and Drug Administration, the APS, and the AAPM convened a consensus meeting of experts to develop an acute pain taxonomy using prevailing evidence. Key issues pertaining to the distinct nature of acute pain are presented followed by the agreed-upon taxonomy. The ACTTION-APS-AAPM Acute Pain Taxonomy will include the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Future efforts will consist of working groups utilizing this taxonomy to develop diagnostic criteria for a comprehensive set of acute pain conditions. Perspective The ACTTION-APS-AAPM Acute Pain Taxonomy (AAAPT) is a multidimensional acute pain classification system designed to classify acute pain along the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Conclusions Significant numbers of patients still suffer from significant acute pain, despite the advent of modern multimodal analgesic strategies. Mismanaged acute pain has a broad societal impact as significant numbers of patients may progress to suffer from chronic pain. An acute pain taxonomy provides a much-needed standardization of clinical diagnostic criteria, which benefits clinical care, research, education, and public policy. For the purposes of the present taxonomy, acute pain is considered to last up to seven days, with prolongation to 30 days being common. The current understanding of acute pain mechanisms poorly differentiates between acute and chronic pain and is often insufficient to distinguish among many types of acute pain conditions. Given the usefulness of the AAPT multidimensional framework, the AAAPT undertook a similar approach to organizing various acute pain conditions.

OBJECTIVE: With the increasing societal awareness of the prevalence and impact of acute pain, there is a need to develop an acute pain classification system that both reflects contemporary mechanistic insights and helps guide future research and treatment. Existing classifications of acute pain conditions are limiting, with a predominant focus on the sensory experience (eg, pain intensity) and pharmacologic consumption. Consequently, there is a need to more broadly characterize and classify the multidimensional experience of acute pain.SETTING: Consensus report following expert panel involving the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), American Pain Society (APS), and American Academy of Pain Medicine (AAPM).METHODS: As a complement to a taxonomy recently developed for chronic pain, the ACTTION public-private partnership with the US Food and Drug Administration, the APS, and the AAPM convened a consensus meeting of experts to develop an acute pain taxonomy using prevailing evidence. Key issues pertaining to the distinct nature of acute pain are presented followed by the agreed-upon taxonomy. The ACTTION-APS-AAPM Acute Pain Taxonomy will include the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Future efforts will consist of working groups utilizing this taxonomy to develop diagnostic criteria for a comprehensive set of acute pain conditions.PERSPECTIVE: The ACTTION-APS-AAPM Acute Pain Taxonomy (AAAPT) is a multidimensional acute pain classification system designed to classify acute pain along the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms.CONCLUSIONS: Significant numbers of patients still suffer from significant acute pain, despite the advent of modern multimodal analgesic strategies. Mismanaged acute pain has a broad societal impact as significant numbers of patients may progress to suffer from chronic pain. An acute pain taxonomy provides a much-needed standardization of clinical diagnostic criteria, which benefits clinical care, research, education, and public policy. For the purposes of the present taxonomy, acute pain is considered to last up to seven days, with prolongation to 30 days being common. The current understanding of acute pain mechanisms poorly differentiates between acute and chronic pain and is often insufficient to distinguish among many types of acute pain conditions. Given the usefulness of the AAPT multidimensional framework, the AAAPT undertook a similar approach to organizing various acute pain conditions.

This randomized, double-blind, placebo-controlled, multicenter, 2-period crossover study (two 6-week treatment periods separated by a 2-week washout period) evaluated the efficacy and safety of pregabalin (150 to 300 mg/d) for treatment of pain and pain on walking in patients with painful diabetic peripheral neuropathy (DPN) who experienced pain while walking.Co-primary efficacy endpoints were: (1) mean pain score (last 7 daily pain diary scores, 0 to 10 numeric rating scale at end of each treatment period) and (2) DPN pain on walking (0 to 10 numeric rating scale immediately after walking 50 feet [15.2 m] on flat surface). Secondary endpoints included other pain parameters, patient-reported sleep, health-related quality of life, and safety measures.Two hundred three patients were treated (pregabalin, n=198; placebo, n=186), with no statistically significant treatment difference for pregabalin versus placebo in the co-primary efficacy endpoints, mean DPN pain (P=0.0656) and mean DPN pain on walking (P=0.412). A carryover effect was observed. Analysis of co-primary endpoints for period 1 showed significant treatment difference for DPN pain (P=0.034) and DPN pain on walking (P=0.001). Treatment with pregabalin resulted in significant improvements versus placebo on prespecified patient global impression of change (end of period 1; P=0.002), and sleep interference rating scale (end of period 2; P=0.011). Adverse events were more frequent with pregabalin than with placebo and caused discontinuation in 13 (6.6%) pregabalin patients versus 5 (2.7%) placebo patients.Failure to meet the co-primary objectives may be related to carryover effect from period 1 to period 2, lower pregabalin dose (150 to 300 mg/d), and/or placebo response in painful DPN.

Background: HIV-related neuropathic pain (HIV-NeP) is common; however, the burden of HIV-NeP is not well-understood. Methods: The cross-sectional study aimed to characterize the HIV-NeP burden. A total of 103 patients with HIV-NeP recruited during routine office visits completed a questionnaire to assess patient-reported outcomes, including pain severity, health status, sleep, mood, and lost productivity. Physicians completed a 6-month retrospective chart review. Results: The sample was predominantly male and not employed for pay. A majority (75.7%) of patients experienced moderate or severe pain. Pain interference, general health, physical health, and depression were worse among patients with more severe pain (all Ps < .006). Most (87.4%) patients were prescribed at least 1 medication for NeP. HIV-related neuropathic pain was associated with 36.1% work impairment. Adjusted annualized costs increased with increasing pain severity ( P < .0001). Conclusion: The impact of HIV-NeP on health status, physical function, and depression increases with severity, resulting in substantial clinical and economic burden.

We present an up-to-date summary of the scientific evidence on (1) the diagnostic value of neural blockade in radiculopathy, peripheral neuropathic pain, and complex regional pain syndrome; (2) the therapeutic value of neural blockade on peripheral trauma-related neuropathic pain, herpes zoster, postherpetic neuralgia, lumbosacral and cervical radiculopathy, failed back surgery syndrome with prominent radicular symptoms, complex regional pain syndrome, trigeminal neuralgia, and painful diabetic and other peripheral neuropathies; and (3) the efficacy of neural destructive techniques and pulse radiofrequency on postherpetic neuralgia, cervical and lumbosacral radiculopathy, and sympathetically maintained pain. The evidence for efficacy is, at the best, moderate, and is often limited or conflicting.

Marco D DiBonaventura,1 Alesia Sadosky,2 Kristen Concialdi,1 Markay Hopps,2 Ian Kudel,1 Bruce Parsons,2 Joseph C Cappelleri,3 Patrick Hlavacek,2 Andrea H Alexander,2 Brett R Stacey,4 John D Markman,5 John T Farrar6 1Health Outcomes Practice, Kantar Health, 2Pfizer Inc, New York, NY, 3Pfizer Inc, Groton, CT, 4University of Washington, Seattle, WA, 5University of Rochester School of Medicine and Dentistry, Rochester, NY, 6University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, US Background: The prevalence of neuropathic pain (NeP) has been estimated within specific health conditions; however, there are no published data on its broad prevalence in the US. The current exploratory study addresses this gap using the validated PainDetect questionnaire as a screener for probable NeP in a general-population health survey conducted with a multimodal recruitment strategy to maximize demographic representativeness. Materials and methods: Adult respondents were recruited from a combination of Internet panels, telephone lists, address lists, mall-based interviews, and store-receipt invitations using a random stratified-sampling framework, with strata defined by age, sex, and race/ethnicity. Older persons and minorities were oversampled to improve prevalence estimates. Results were weighted to match the total adult US population using US Census data. Demographic information was collected, and respondents who experienced physical pain in the past 12 months completed the PainDetect and provided additional pain history. A cutoff score of 19 or greater on the PainDetect was used to define probable NeP. Results: A total of 24,925 respondents (average response rate 2.5%) provided demographic data (52.2% female, mean age 51.5 years); 15,751 respondents reported pain (63.7%), of which 2,548 (15.7%, 95% confidence interval 14.9%–16.5%) had probable NeP based on the PainDetect, which was 10% (95% confidence interval 9.5%–10.5%) of all respondents. Among those reporting pain, the prevalence of probable NeP among Blacks and Hispanics was consistently higher than Whites in each age- and sex group. The highest prevalence among those with pain was among male Hispanics 35–44 years (32.4%) and 45–54 years (24.2%) old. The most commonly used medications reported by those with probable NeP were nonsteroidal anti-inflammatory drugs (44.2%), followed by weak opioids (31.7%), antiepileptics (10.9%), and strong opioids (10.9%). Conclusion: This is the first study to provide an estimate of the prevalence of probable NeP in the US, showing significant variation by age and ethnicity. Keywords: neuropathic pain, prevalence, pain types, epidemiology

Bruce Parsons,1 Caroline Schaefer,2 Rachael Mann,3 Alesia Sadosky,1 Shoshana Daniel,4 Srinivas Nalamachu,5 Brett R Stacey,6 Edward C Nieshoff,7 Michael Tuchman,8 Alan Anschel91Pfizer, Inc, New York, NY, USA; 2Covance Market Access Services, Inc, Gaithersburg, MD, USA; 3Covance Market Access Services, Inc, San Diego, CA, USA; 4Covance Market Access Services, Inc, Conshohocken, PA, USA; 5International Clinical Research Institute, Overland Park, KS, USA; 6Oregon Health and Science University, Portland, OR, USA; 7Rehabilitation Institute of Michigan/Wayne State University, Detroit, MI, USA; 8Palm Beach Neurological Center, Palm Beach Gardens, FL, USA; 9Rehabilitation Institute of Chicago, Chicago, IL, USABackground: Neuropathic pain (NeP) can be chronic, debilitating, and can interfere with sleep, functioning, and emotional well being. While there are multiple causes of NeP, few studies have examined the disease burden and treatment patterns associated with post-traumatic/post-surgical (PTPS) NeP.Objective: To characterize pain, health status, function, health care resource utilization, lost productivity, and costs among subjects with PTPS NeP in the United States.Methods: This observational study enrolled 100 PTPS NeP subjects recruited during routine visits from general practitioner and specialist sites. Subjects completed a one-time questionnaire with validated measures of pain severity and pain interference, health status, sleep, anxiety and depression, productivity, and study-specific items on demographics, employment status, and out-of-pocket expenses. Investigators completed a case report form based on a 6-month retrospective chart review, recording subjects' clinical characteristics as well as current and previous medications/treatments for NeP. Subjects were stratified into mild, moderate, and severe pain groups.Results: Subjects' demographic characteristics were: mean age of 54.9 years, 53% female, and 22% employed for pay. Mean pain severity score was 5.6 (0–10 scale), with 48% and 35% classified as having moderate and severe pain, respectively. The mean number of comorbidities increased with greater pain severity (P = 0.0009). Patient-reported outcomes were worse among PTPS NeP subjects with more severe pain, including pain interference with function, health state utility, sleep, and depression (P < 0.0001). Eighty-two percent of subjects were prescribed two or more NeP medications. The total mean annualized adjusted direct and indirect costs per subject were $11,846 and $29,617, respectively. Across pain severity levels, differences in annualized adjusted direct and indirect costs were significant (P < 0.0001).Conclusion: PTPS NeP subjects reported high pain scores, which were associated with poor health utility, sleep, mood, and function, as well as high health care resource utilization and costs. The quality of life impact and costs attributable to PTPS NeP suggest an unmet need for effective and comprehensive management.Keywords: trauma/surgery, neuropathic pain, quality-of-life, patient-reported outcomes, costs, productivity

Preclinical and clinical studies suggest that neuronal nicotinic receptor (NNR) agonists may be a novel and effective therapy for numerous painful conditions. Analgesic efficacy and safety of the highly selective α(4)β(2) NNR agonist ABT-894 was evaluated in 2 separate randomized, double-blind, multicenter, placebo-controlled clinical trials in patients with diabetic peripheral neuropathic pain (DPNP). Study 1 (280 patients randomized) tested 1, 2, and 4 mg ABT-894 twice daily compared with placebo and 60 mg duloxetine once per day over 8 weeks of treatment. Study 2 (124 patients randomized) tested 6 mg ABT-894 twice daily vs placebo for 8 weeks. The primary efficacy outcome measure in both studies was the weekly mean of the 24-hour average pain score recorded in each patient's diary. In both trials, none of the ABT-894 dose groups showed efficacy compared with placebo, whereas duloxetine achieved a statistically significant improvement over placebo in Study 1. All dose levels of ABT-894 were well tolerated, and no significant safety issues were identified. These results are in contrast to the outcome of a previously reported study of DPNP using the less selective α(4)β(2) NNR agonist ABT-594, which demonstrated efficacy compared with placebo, albeit with significant tolerability limitations. The failure of the highly selective α(4)β(2) NNR agonist ABT-894 indicates that it may not be possible to define a therapeutic index for this mechanism or that selectively targeting α(4)β(2) NNRs may not be a viable approach to treating neuropathic pain.

Objective: To evaluate the use and direct medical costs of pharmacologic and alternative treatments for patients with osteoarthritis (OA) and chronic low back pain (CLBP). Methods: The LifeLink™ Health Plan Claims Database was used to identify patients ≥18 years old, diagnosed with OA (N = 112,951) or CLBP (N = 101,294). Of these patients, 64,085 with OA and 47,386 with CLBP received pain-related treatments during CY2008 and were selected for inclusion. For patients in both cohorts, pharmacologic and alternative treatments, and direct medical costs were examined during CY2008. Results: Opioids were the most frequently prescribed medication (>70%) in both groups, followed by nonselective nonsteroidal anti-inflammatory drugs (>50%). Over 30% received antidepressants, >20% received benzodiazepines, and 15% in each group received sedative hypnotics. Use of alternative treatments was as follows: chiropractor, OA 11%, CLBP 34%; physical therapy, 20% in both groups; transcutaneous electrical nerve stimulations (TENS), OA 14%, CLBP 22%; acupuncture, hydrotherapy, massage therapy, and biofeedback

Objective To examine patterns of pharmacotherapy and health care utilization and costs prior to total knee replacement (TKR) or total hip replacement (THR) in patients with osteoarthritis (OA). Methods Using a large US health insurance claims database, we identified all patients with OA who were ages ≥40 years and had undergone TKR or THR between January 1, 2006 and December 31, 2007. Patients with

Comorbidities and resource utilization among patients with osteoarthritis (OA) in clinical practice have been infrequently characterized. The purpose of this study was to examine comorbidities, pain-related pharmacotherapy, and direct medical costs of patients with OA in clinical practice.This retrospective cohort analysis used medical and pharmacy claims data from the LifeLink™ Database. OA patients (ICD-9-CM codes 715.XX) were matched (age, gender, and region) with individuals without OA. Comorbidities, pain-related pharmacotherapy, and direct medical costs (pharmacy, outpatient, inpatient, total) were examined for the calendar year 2008.The sample consisted of 112,951 OA patients and 112,951 controls (mean age: 56.9 [SD=9.5] years; 62% female). Relative to controls, OA patients were significantly more likely (p0.0001) to have comorbidities, including musculoskeletal (84.3 vs. 37.1%) and neuropathic pain (22.0 vs. 6.1%) conditions, depression (12.4 vs. 6.4%), anxiety (6.6 vs. 3.5%), and sleep disorders (11.9 vs. 4.2%). OA patients were significantly more likely (p0.0001) to receive pain-related medications, including opioids (40.7 vs. 17.1%), NSAIDs (37.1 vs. 11.5%), tramadol (9.8 vs. 1.8%), and adjunctive medications for treating depression, anxiety, and insomnia. Mean [SD] total direct medical costs were more than two times higher among OA patients ($12,905 [$21,884] vs. $5099 [$13,855]; p0.001) and median costs were more than three times higher ($6188 vs. $1879; p0.0001). Study limitations include potential errors in coding and recording; overestimation of the comorbidity burden; inability to link condition of interest, OA, with prescribed medications; and possible underestimation of the true costs of OA, because indirect costs were not considered and the direct costs were from a third party payer (commercial insurance) perspective.The patient burden of OA was characterized by a high prevalence of comorbidities. The payer burden was also substantial, with significantly greater use of pain-related and adjunctive medications, and higher direct medical costs.

Currently, an estimated 38 million individuals 65 years or older live in the United States, and more than 11 million of these individuals are 80 years or older. Older people are at high risk of neuropathic pain because many diseases that cause neuropathic pain increase in incidence with age. Depending on their underlying health, older adults with neuropathic pain may have to cope with multiple coexisting diseases, polypharmacy, and impaired functional ability. The objective of this article is to review how aging and frailty affect the treatment of older adults with neuropathic pain. Specific topics reviewed include the complexity of treatment decisions in older patients due to aged heterogeneity, multimorbidity, and polypharmacy; selection of treatment in an effort to maximize patients' functional abilities in addition to relieving their pain; more careful dosing (usually lower) and monitoring of pharmacotherapy relative to younger patients due to age-related changes in pharmacokinetics and pharmacodynamics; and underrepresentation of older adults in clinical trials of neuropathic pain treatments, which further compromises physicians' ability to make informed treatment decisions.

Objective. Neuropathic pain associated with postherpetic neuralgia (PHN) and painful diabetic peripheral neuropathy (DPN) can be intractable and may not respond to commonly used treatments, such as tricyclic antidepressants (TCAs) and opioids. This long-term, open-label study was a preliminary evaluation of pregabalin for patients whose pain had been judged refractory to other treatments for neuropathic pain. Design. Patients had previously participated in double-blind, placebo-controlled, randomized trials of pregabalin in DPN and PHN. They had moderate to severe neuropathic pain despite treatment with gabapentin, a TCA, and a third medication (e.g., other anticonvulsants, opioid, selective serotonin reuptake inhibitor, tramadol). Flexible-dosage pregabalin 150–600 mg/day was taken for 3-month periods followed by 3- to 28-day pregabalin “drug holidays,” with an analysis up to 15 months (five treatment cycles). Pain intensity was measured using the visual analog scale of the Short-Form McGill Pain Questionnaire. Results. In total, 81 patients were included in this analysis. Pregabalin 150–600 mg/day was associated with clinically meaningful and sustained pain reduction during each treatment cycle. During pregabalin “drug holidays,” pain quickly returned to baseline levels; it was reduced again when pregabalin was reinstated. Conclusions. These results suggest that pregabalin may be beneficial in patients with neuropathic pain who have had an unsatisfactory response to treatment with other medications.

Time to onset of pain relief and improvement in allodynia in 269 patients with postherpetic neuralgia was examined in a 4-week randomized trial comparing flexibly dosed pregabalin (150–600 mg/d), fixed-dose pregabalin (300 mg/d), and placebo. For each patient with clinically meaningful pain reduction (≥30%) at end point, onset of pain relief was defined as the first study day on which a patient reported ≥1-point reduction in pain relative to baseline. Average dose achieved was 396 mg/d in the flexible-dose group compared with 295 mg/d in the fixed-dose group. Median pain relief onset times were 3.5 days (flexible-dose), 1.5 days (fixed-dose), and >4 weeks (placebo). Compared with placebo, significantly more patients in both pregabalin treatment groups achieved ≥30% and ≥50% pain reduction at end point. Almost 95% of patients had brush-evoked allodynia, with 68% having moderate to severe allodynia (≥40/100 mm). At baseline, pain and allodynia were highly correlated. Independent of treatment assignment, improvement in pain and improvement in allodynia were significantly correlated. Allodynia could serve as a useful surrogate outcome measure in future studies. Pregabalin was significantly better than placebo in alleviating allodynia (flexible-dose reduction, 26 mm; fixed-dose, 21 mm; placebo, 12 mm). Discontinuation rates due to adverse events were more frequent in the fixed-dose group. Perspective A flexible-dose regimen reduces discontinuations, facilitates higher final doses, and results in a slightly greater pain relief. Allodynia (touch-evoked pain) can be of disabling severity and is present in nearly all patients with postherpetic neuralgia. Allodynia severity is correlated with pain severity and improvement in allodynia is correlated with clinical response.

Both gabapentin and pregabalin are approved for the management of postherpetic neuralgia (PHN), although dosing and pharmacokinetic differences between these medications may affect their use in actual practice.This study was conducted to characterize the use of gabapentin and pregabalin in the management of PHN in clinical practice, with a specific focus on the doses actually prescribed and changes in the use of other neuropathic pain-related medications after the initiation of gabapentin or pregabalin.The PharMetrics Patient-Centric Database was used to identify patients with PHN who were newly prescribed gabapentin or pregabalin between September 1, 2005, and March 31, 2006. The out-comes of interest were the prevalence of comorbidities, exposure to neuropathic pain-related medications (ie, the proportions of patients receivingor=1 prescription for these medications in the 6-month periods before and after the date of the first gabapentin or pregabalin prescription), and attainment of therapeutic dose levels (gabapentin,or=1800 mg/d; pregabalin,or=150 mg/d).The database search identified 151 patients with PHN who were newly prescribed gabapentin (57.0% female; mean [SD] age, 55.8 [11.3] years) and 100 patients who were newly prescribed pregabalin (62.0% female; mean age, 52.8 [9.4] years). The prevalence of comorbidities did not differ significantly between recipients of prescriptions for gabapentin or pregabalin, with the exception of hyperlipidemia, which was more prevalent in those prescribed gabapentin (33.8% vs 22.0%, respectively; P = 0.044), and depression, which was more prevalent in those prescribed pregabalin (12.0% vs 4.6%, respectively; P = 0.031). In the pretreatment period, those who were prescribed pregabalin had significantly greater use of long-acting opioids (P = 0.005), anticonvulsants (P0.001), selective norepinephrine reuptake inhibitors (P0.001), and the lidocaine 5% patch (P = 0.005) compared with those prescribed gabapentin. Use of any opioid increased from pretreatment to follow-up in those prescribed gabapentin, significantly so in those who receivedor=2 opioid prescriptions (P = 0.016). Use of any opioid decreased significantly from pre-treatment to follow-up in those prescribed pregabalin (P = 0.005), particularly in those who receivedor=2 opioid prescriptions (P = 0.004). Tramadol use decreased significantly in those prescribed gabapentin (P = 0.045), and anticonvulsant use decreased significantly in those prescribed pregabalin (P = 0.004). Among patients prescribed gabapentin or pregabalin who received 1 prescription, 2 consecutive prescriptions, andor=3 consecutive prescriptions, a greater proportion of those prescribed pregabalin attained therapeutic dose levels by their first, second, and third consecutive prescriptions compared with those prescribed gabapentin (69.0% vs 3.5%, respectively [P0.001]; 71.4% vs 21.7% [P0.001]; and 89.3% vs 46.2% [P0.001], respectively).In these patients with PHN in the usual-care setting, opioid use increased after the initiation of gabapentin and decreased after the initiation of pregabalin. Few of those prescribed gabapentin received a prescription for a therapeutic dose, whereas a greater proportion of patients who were prescribed pregabalin received a prescription for a therapeutic dose.

The objective of this article is to provide evidence-based recommendations for the management of patients with herpes zoster (HZ) that take into account clinical efficacy, adverse effects, impact on quality of life, and costs of treatment. Systematic literature reviews, published randomized clinical trials, existing guidelines, and the authors' clinical and research experience relevant to the management of patients with HZ were reviewed at a consensus meeting. The results of controlled trials and the clinical experience of the authors support the use of acyclovir, brivudin (where available), famciclovir, and valacyclovir as first-line antiviral therapy for the treatment of patients with HZ. Specific recommendations for the use of these medications are provided. In addition, suggestions are made for treatments that, when used in combination with antiviral therapy, may further reduce pain and other complications of HZ.

Most patients with chronic pain receive multimodal treatment. There is scant literature to guide us, but when approaching combination pharmacotherapy, the practitioner and patient must weigh the benefits with the side effects; many medications have modest effect yet carry significant side effects that can be additive. Chronic pain often leads to depression, anxiety, and deconditioning, which are targets for treatment. Structured interdisciplinary programs are beneficial but costly. Interventions have their place in the treatment of chronic pain and should be a part of a multidisciplinary treatment plan. Further research is needed to validate many common combination treatments.

Our goal was to assess the patient-level burden among subjects with painful diabetic peripheral neuropathy (DPN). Community-based physicians recruited patients with painful DPN ( N = 255) between April and October 2003. Patients completed a survey on pain experience (Brief Pain Inventory-DPN [BPI-DPN]), health status (EuroQoL [EQ-5D]), healthcare utilization (consults, prescription [Rx], and over-the-counter [OTC] medications), and work productivity/functioning. Patients were 61 ± 12.8 years old and had diabetes for 12 ± 10.3 years and painful DPN for 6.4 ± 6.4 years; 25.5 and 62.7% had other neuropathic and musculoskeletal pain conditions. Average and worst pain scores (BPI-DPN, 0-10 scales) were 5.0 ± 2.5 and 5.6 ± 2.8. The mean EQ-5D utility was .5 ± .3 (range = −.594-1). A majority (87.4%) took pain medications (Rx/OTC) in the preceding week: an average of 3.8 ± 3.9 Rx and 2.1 ± 1.3 OTC medications. Nearly half (46.7%) received NSAIDs. Other frequently reported medications were short/long-acting opioids (43.1%), anticonvulsants (27.1%), selective serotonin reuptake inhibitors/selective norepinephrine reuptake inhibitors (18%), and tricyclic antidepressants (11.4%). During the preceding 3 months, 59.6% had ≥2 health professional consults; 59% reported decreased home productivity; 85.5% reported activity limitations; and 64.4% of patients who worked ( N = 73) reported missing work/decreased work productivity due to painful DPN. Our results underscore a substantial patient-level burden among subjects with painful DPN. Perspective Information on the patient-level burden among painful DPN sufferers in the U.S. was previously lacking. Our results suggest that this burden is significant, evidenced by moderate-to-high pain levels, polypharmacy, health resource use, and work/activity limitations. Results also suggest suboptimal pain management and low levels of satisfaction with treatments.

Our goal was to evaluate pain severity, pain-related interference with function, sleep impairment, symptom levels of anxiety and depression, and quality of life among patients with painful diabetic peripheral neuropathy (DPN). Participants in a burden of illness survey (n = 255) completed the modified Brief Pain Inventory-DPN (BPI-DPN), MOS Sleep Scale, Hospital Anxiety and Depression Scale (HADS), Short Form Health Survey-12v2 (SF-12v2), and the EuroQoL (EQ-5D). Patients were 61 +/- 12.8 years old (51.4% female), had diabetes for 12 +/- 10.3 years and painful DPN for 6.4 +/- 6.4 years. Average and Worst Pain scores (BPI-DPN, 0-10 scales) were 5.0 +/- 2.5 and 5.6 +/- 2.8. Pain substantially interfered (or=4 on 0-10 scales) with walking ability, normal work, sleep, enjoyment of life, mood, and general activity. Moderate to severe symptom levels of anxiety and depression (HADS-A and HADS-D scoresor=11 on 0-21 scales) occurred in 35% and 28% of patients, respectively. Patients reported greater sleep problems compared with the general U.S. population and significant impairment in both physical and mental functioning (SF-12v2) compared with subjects with diabetes. The mean EQ-5D utility score was 0.5 +/- 0.3. Greater pain levels in DPN (mild to moderate to severe) corresponded with higher symptom levels of anxiety and depression, more sleep problems, and lower utility ratings and physical and mental functioning, (all Ps0.01). Painful DPN is associated with decrements in many aspects of patients' lives: physical and emotional functioning, affective symptoms, and sleep problems. The negative impact is higher in patients with greater pain severity.

Neuropathic pain results from a variety of medical conditions encountered in physiatric practice, including infection, trauma, metabolic abnormalities, and nerve compression. Unlike pain resulting from nociceptive or inflammatory processes, neuropathic pain is associated with primary lesion or dysfunction of the nervous system itself and is often difficult to treat. Existing treatment options include drug therapy (e.g., anticonvulsants, the lidocaine patch 5%, antidepressants, opioids, tramadol) or interventional treatments (e.g., peripheral or neuraxial nerve blockade, implanted spinal cord stimulators, implanted intrathecal catheters). The following article presents an overview of the cellular mechanisms associated with neuropathic pain, summarizes the results of randomized, controlled trials with the major classes of available drugs, and discusses treatment options that provide a rational basis for pharmacotherapy.

The influence of sensory symptoms on overall simple pain ratings in neuropathic pain is not well understood. The goal of this study was to determine this relationship by using the Neuropathic Pain Questionnaire (NPQ) and Neuropathic Pain Scale (NPS) in patients who had neuropathic pain. Overall pain intensity ratings were assessed by means of Average and Worst Pain ratings from the Brief Pain Inventory. Ongoing average pain was rated as 5.7 and worst pain as 7.7 on 0 to 10 scale, and it was present in 96% of patients, whereas symptoms that are commonly studied in the laboratory, such as increased pain due to touch and due to heat, were much less frequent (64% and 38%, respectively). Worst pain was most highly correlated with shooting, stabbing, and distress symptom complex, which was in contrast to Average pain, which was most highly correlated with symptom complex consisting of a large number of items. Analysis of conceptually related thermal heat sensation types of pain, spontaneous “burning” pain and the evoked pain “increased due to heat,” showed that spontaneous burning pain was reported at much higher frequency and intensity than the evoked increased pain due to heat. There was no statistically significant difference between descriptors from NPS and NPQ among subgroups of neuropathic pain, such as polyneuropathy, radiculopathy, or posttraumatic neuralgia, but this could be in part due to relatively small number of patients in these subgroups of neuropathic pain. Quantitative analysis, as performed in this study, is one of the steps in developing an approach for elucidating the relationship between neuropathic pain symptoms and underlying mechanisms. Perspective Assessment of neuropathic pain symptoms by means of specifically designed questionnaires provides significant insight into patients' pain experience, including pain overall, which is under many influences. Further research of this type can contribute to advances in mechanism-based diagnosis and treatment.

Postherpetic neuralgia (PHN), which affects up to 70% of elderly persons with herpes zoster, can have debilitating effects, including physical and social disability and significant psychological distress. A variety of agents have been used, either singly or in combination, to control PHN, including topical and oral analgesics, antidepressants, and antiepileptic drugs (AEDs). However, PHN often proves refractory to these therapies.This article reviews available data on the use of the newer AED gabapentin for the control of PHN.A MEDLINE search was undertaken to identify all randomized, placebo-controlled trials on the use of gabapentin in PHN. The search terms were gabapentin and postherpetic neuralgia.The literature search identified 2 published studies of the efficacy of gabapentin in a total of 563 patients with PHN that had persisted for at least 3 months after the healing of herpes zoster rash. The studies employed multiple outcome measures, including visual analog and Likert scales for pain intensity, and quality-of-life and functional measures that included the Medical Outcomes Study 36-item Short Form Health Survey (SF-36) and the Profile of Mood States. At maximum target dosages of 1800 to 3600 mg/d, gabapentin produced significant reductions in mean daily pain scores compared with placebo on both visual analog(P0.001) and Likert scales (P0.01). Improvements were also seen on the SF-36 subscales for physical functioning, bodily pain, vitality, and mental health(P0.01).Gabapentin may provide benefits in terms of alleviation of pain and overall quality of life in patients with chronic PHN.

Caroline Schaefer,1 Alesia Sadosky,2 Rachael Mann,3 Shoshana Daniel,4 Bruce Parsons,2 Michael Tuchman,5 Alan Anschel,6Brett R Stacey,7 Srinivas Nalamachu,8 Edward Nieshoff9 1Covance Market Access Services Inc., Gaithersburg, MD, 2Pfizer, Inc., New York, NY, 3Covance Market Access Services Inc., San Diego, CA, 4Covance Market Access Services Inc., Conshohocken, PA, 5Palm Beach Neurological Center, Palm Beach Gardens, FL, 6Rehabilitation Institute of Chicago, Chicago, IL, 7Oregon Health and Science University, Portland, OR, 8International Clinical Research Institute, Overland Park, KS, 9Rehabilitation Institute of Michigan/Wayne State University, Detroit, MI, USABackground: As with many chronic conditions, patients with neuropathic pain (NeP) are high consumers of health care resources. However, limited literature exists on the economic burden of NeP, including its impact on productivity. The aim of this study was to characterize health care resource utilization, productivity, and costs associated with NeP by pain severity level in US adults.Methods: Subjects (n=624) with painful diabetic peripheral neuropathy, human immunodeficiency virus-related peripheral NeP, post-trauma/post-surgical NeP, spinal cord injury with NeP, chronic low back pain with NeP, and small fiber neuropathy were recruited during routine office visits to US community-based general practitioners and specialists. Clinicians captured clinical characteristics, NeP-related medications, and health care resource utilization based on 6-month retrospective medical chart review. Subjects completed questionnaires on demographics, pain/symptoms, costs, and productivity. Brief Pain Inventory pain severity scores were used to classify subjects by mild, moderate, or severe pain. Annualized NeP-related costs (adjusted for covariates) were estimated, and differences across pain severity groups were evaluated.Results: In total, 624 subjects were recruited (mean age 55.5±13.7 years; 55.4% male), and 504/624 (80.8%) reported moderate or severe pain. Statistically significant differences were observed across pain severity levels for number of comorbidities, prescription medications, physician office visits, and lost productivity (all P≤0.0001). At all pain severity levels, indirect costs were the primary cost driver. After adjusting for demographic and clinical variables, total mean (95% confidence interval [CI]) annualized direct medical costs to payers, direct costs to subjects, and indirect costs per subject were US$6,016 (95% CI 5,316–6,716), US$2,219 (95% CI 1,919–2,519), and US$19,000 (95% CI 17,197–20,802), respectively, with significant differences across pain severity levels.Conclusion: Subjects with NeP, mainly those showing moderate or severe pain, had significant associations between pain severity and NeP-related health care resource utilization, productivity, and costs. The economic burden, particularly indirect costs, was highest among those with severe pain and higher than previously reported in studies of specific NeP conditions. Keywords: burden of illness, neuropathic pain management, health care costs, health care resource use, productivity

Objective The aim of this study was to evaluate patient-reported burden associated with peripheral and central neuropathic pain (NeP) by pain severity and NeP condition. Design Six hundred twenty-four subjects with one of six NeP conditions were recruited during routine office visits. Subjects consented to retrospective chart review and completed a one-time questionnaire (including EuroQol-5 dimensions, 12-item Short-Form Health Survey, Brief Pain Inventory-Short Form, Medical Outcomes Study Sleep Scale, Hospital Anxiety and Depression Scale, and demographic and clinical characteristics). Pain severity scores were used to stratify subjects by mild, moderate, and severe pain. Summary statistics and frequency distributions were calculated. Differences by severity level were compared using Kruskal–Wallis (continuous variables) and chi-square or Fisher's exact test (categorical variables). Effect size was computed with Cohen's d (mild vs severe). Results Subjects' mean age was 55.5. The majority (80.8%) had moderate or severe pain. Patient-reported outcomes (health status, physical and mental health, pain interference with function, sleep, anxiety, and depression) were significantly worse among subjects with greater pain severity (all P < 0.0001). Severe pain subjects were negatively impacted by ≥30% in each outcome compared with mild pain subjects; standardized effect size was moderate for anxiety (0.59) and large (>0.95) for all others. The observed burden was most substantial among chronic low back pain-NeP, although the pattern of disease burden was similar across the six NeP conditions. Conclusions Subjects across NeP conditions exhibited high pain levels, which were significantly associated with poor function, compromised health status and sleep, and increased anxiety and depression. Results indicate substantial patient burden across broad NeP, particularly among subjects with severe pain.

The proportion of patients with intractable pain successfully managed with spinal cord stimulation (SCS) remains disputed. We analyze 27 consecutive patients with intractable pain treated with SCS using identical hardware (Itrel II System; Medtronic Neurological, Inc Minneapolis, MN, USA) by a single satisfactory diagnosis 1992 through 1995. A rigid selection protocol was used: 1. A satisfactory diagnosis of the pathologic process resulting in pain was made. 2. A corrective surgical procedure was judged not feasible by surgeons experienced in the particular pathology, e.g., vascular peripheral nerve, spine. 3. Lack of satisfactory response to noninterventional pain management modalities by an interdisciplinary pain clinic. 4. Independent psychological evaluation, including a structured interview was performed by a psychologist specialized in chronic pain management. In the last eight cases, a battery of self-report tests designed to assess psychosocial and behavioral consequences of the chronic pain problem were administered as well. All cases were of nonmalignant pain, except for one patient. Thirteen cases were diagnosed with failed back surgery syndrome (FBSS), one older patient with lumbosacral radiculopathy who refused decompression, one cervical radiculopathy and Klippel-Feil syndrome, six with reflex sympathetic dystrophy (RSD), two with peripheral vascular ischemic disease, one with post-thoracotomy pain syndrome, one with leg pain following resection of angiolipoma, one with traumatic superficial peroneal neuropathy, and one with Pancoast's tumor. Fifteen patients were female and twelve were male. All were Caucasian. Their ages ranged from 27 to 84 years (mean:48). The average follow-up was 21 months (range: 48-6). All patients underwent a three day trial screening with Pisces-Quad/Resume epidural leads connected to a temporary external stimulator. An Itrel II System pulse-generator was internalized in each of the 24 patients who had successful trial (three cervical and twenty-one thoracic-lumbar). There was no morbidity. Pain reduction was sustained in 22 out of the 24 patients who continue to use the stimulator. The same number would choose to receive in an electrical stimulator again. Normalization or improvement in Quantitative Sudomotor Axon Reflex Test (Q-SART) and Thermography was documented in the patients with RSD. We conclude that rigid selection protocol can maximize the proportion of patients with intractable pain who are successfully treated with SCS. Strict neurosurgical technique eliminates infection risk. Hardware selection minimizes incidence of malfunction.

Background Chronic low back pain (CLBP) is highly prevalent, and between 35% and 55% of individuals with CLBP suffer from a neuropathic pain component (CLBP-NeP). Limited data on the economic and patient burden in this CLBP subgroup have been published. Methods This observational study aimed to characterize burden among CLBP-NeP subjects (n=106) recruited during routine physician visits in the United States. Subjects completed a questionnaire to capture pain severity, function, health status, sleep, anxiety/depression, lost productivity, demographics, employment status, and out-of- pocket expenses. Investigators completed a 6-month retrospective chart review to capture clinical characteristics and CLBP-NeP-related healthcare resource use. Based on average pain severity scores, subjects were stratified into mild, moderate, and severe pain groups. Summary statistics were calculated, and differences across severity groups were evaluated. Results Subjects’ mean (SD) age was 54.1 (11.9) years; 57.5% were female. Most subjects had at least one comorbidity (87.7%); common comorbidities included sleep disturbance/insomnia [58.5%], depressive symptoms [51.9%], headache/migraine [46.2%], and anxiety [45.3%]. Mean (SD) pain severity score was 6.0 (1.77). Outcomes were worse among subjects with greater pain for health status, function, and sleep. Overall, 23.6% of subjects were employed for pay; 32.1% reported being disabled due to CLBP-NeP. Among those employed, lost productivity due to CLBP-NeP (62.3% overall work impairment) was substantial. Nearly all (98.1%) subjects were prescribed one or more medications for CLBP-NeP, including opioids (81.1%), muscle relaxants (33.0%), and antiepileptics (28.3%). Mean adjusted annualized direct and indirect costs per subject were $8,305 and $30,496 (mild), $10,189 and $26,428 (moderate), and $11,880 and $25,051 (severe), respectively, with no significant differences observed. Conclusions Patient and economic CLBP-NeP burden is high despite active management. Sub-optimal outcomes were associated with greater pain severity. Findings point to unmet need and indicate CLBP-NeP burden is experienced in terms of poor function and lost productivity.

Although Patient-Controlled Analgesia (PCA) is routinely available in most hospitals in the United States, there appears to be little standardization regarding who provides this valuable service to postoperative patients. This study evaluates the differences in PCA management practices and patient outcomes between primary service (PS) physicians and acute pain service (APS) physicians. Over a 3-mo period, 40 patients prescribed PCA by PS physicians were prospectively studied without the knowledge of the physicians or nurses involved in PCA management. After collecting PS data, a proportionate stratified random sampling procedure was used to select 40 APS patients matched for gender, age, and type of surgery. Data regarding patient demographics, PCA prescription, changes in PCA orders, opioid consumption, reason for discontinuation of PCA, verbal analog scale pain scores, side effects, and post-PCA pain management were analyzed. Although pain scores were not different between groups, APS patients had fewer side effects, were more likely to receive a loading dose, had their PCA settings adjusted more often (P < 0.05), and used more opioid. PS patients were more likely to receive intramuscular medications after PCA discontinuation (P < 0.05). This study demonstrates potentially important PCA management differences between APS and PS physicians.

RAYNAUD'S Disease is a vasospastic disorder affecting primarily the distal resistance vessels. The disease is typically characterized by the abrupt onset of digital pallor or cyanosis in response to cold exposure or stress. Raynaud's Disease may occur independently or be associated with other conditions (systemic lupus erythematosus and scleroderma) and connective tissue diseases. Initial symptoms may include a burning sensation in the affected area accompanied by allodynia and painful paresthesias with vasomotor (cold, cyanotic) changes. Ultimately, as the ischemia becomes more chronic, this condition may progress to amputation of the affected digits. The most common indication for spinal cord stimulation in the United States is for chronic painful neuropathies. However, in Europe, spinal cord stimulation is frequently used to treat ischemic conditions, such as peripheral vascular disease and coronary occlusive disease. Although technically an off-label indication in the United States, this practice is supported by many published studies. There have also been case reports of its use in other diseases resulting in arterial insufficiency to the extremities, such as thromboangiitis obliterans (Buerger's Disease), 2 but its use in Raynaud's Disease is relatively underreported. 3 This case describes the use of cervical spinal cord stimulation to treat refractory digital ischemia in a patient with advanced Raynaud's Disease.

Neuropathic pain (NP) is often refractory to pharmacologic and non-interventional treatment. On behalf of the International Association for the Study of Pain Neuropathic Pain Special Interest Group (NeuPSIG), the authors evaluated systematic reviews, clinical trials, and existing guidelines for the interventional management of NP. Evidence is summarized and presented for neural blockade, spinal cord stimulation (SCS), intrathecal medication, and neurosurgical interventions in patients with the following peripheral and central NP conditions: herpes zoster and postherpetic neuralgia (PHN); painful diabetic and other peripheral neuropathies; spinal cord injury NP; central post-stroke pain; radiculopathy and failed back surgery syndrome (FBSS); complex regional pain syndrome (CRPS); and trigeminal neuralgia and neuropathy. Due to the paucity of high-quality clinical trials, no strong recommendations can be made. Four weak recommendations based on the amount and consistency of evidence, including degree of efficacy and safety, are: (1) epidural injections for herpes zoster; (2) steroid injections for radiculopathy; (3) SCS for FBSS; and (4) SCS for CRPS type 1. Based on the available data, we recommend not to use sympathetic blocks for PHN nor RF lesions for radiculopathy. No other conclusive recommendations can be made due to the poor quality of available of data. Whenever possible, these interventions should either be part of randomized clinical trials or documented in pain registries. Priorities for future research include randomized clinical trials; long-term studies; and head-to-head comparisons among different interventional and non-interventional treatments.

PreviewDespite the fact that pain is a common presenting complaint, its effective management remains an elusive goal surrounded by contradictions and controversy. In this article, Dr Stacey discusses the goals of chronic pain management and the treatment options available, with a focus on pharmacologic therapy and prescribing issues involving currently available analgesics.

Background. Long-term opioid use has increased substantially over the past decade for U.S. women. Women are more likely than men to have a chronic pain condition, to be treated with opioids, and may receive higher doses. Prescribing trends persist despite limited evidence to support the long-term benefit of this pain treatment approach. Purpose. To review the medical and psychological risks and consequences of long-term opioid therapy in women. Method. Scientific literature containing relevant keywords and content were reviewed. Results and Conclusions. Long-term opioid use exposes women to unique risks, including endocrinopathy, reduced fertility, neonatal risks, as well as greater risk for polypharmacy, cardiac risks, poisoning and unintentional overdose, among other risks. Risks for women appear to vary by age and psychosocial factors may be bidirectionally related to opioid use. Gaps in understanding and priorities for future research are highlighted.

Opioid therapy for chronic noncancer pain has been the topic of debate, including who is an appropriate candidate for prescription, what are correct dosages, and how to prevent opioid-related accidental death. One overlooked aspect of this debate is attention to the sex differences related to the use of opioids and the specific risks for women. Epidemiological studies of pharmacy claims in the United States show that opioids are more likely to be prescribed to women than men and that women are more likely to be taking higher doses of opioids.1 In recent years, opioid prescription has increased among both sexes, but the temporal slope for opioid prescription is greater for women than for men, suggesting that this sex disparity is widening over time.2 Women are at greater risk for acquiring varied chronic pain conditions, and women on average experience greater pain intensity than men. For these reasons, women are at greater risk for the varied iatrogenic consequences of opioid prescription. Also, women are at greater risk for opioid misprescription: the prescribing of opioids for pain conditions such as fibromyalgia, headache, or osteoarthritis, with efficacy data suggesting that opioid therapy is nonbeneficial. While both men and women are at risk for opioid-induced endocrinopathy, 3 several studies have documented that women-specific risks include amenorrhea and infertility in reproductive-aged women and reduced sex steroids in postmenopausal women.4 Hormonal imbalance is associated with increased pain intensity and with the development of secondary complications, such as impaired stress and immune responses. Regarding opioid use in pregnancy, an epidemiological case-controlled study conducted by the Centers for Disease Control and Prevention showed that maternal opioid exposure significantly predicted infant conoventricular septal defect, atrioventricular septal defect, atrial septal defect, hypoplastic left heart syndrome, tetralogy of Fallot, and pulmonary valve stenosis; other risks included spina bifida and gastroschisis.5 The study excluded women who reported illicit opioid use; therefore, the findings are relevant to female pain patients who are considering pregnancy. Studies describing specific risks of opioid exposure in infants of mothers who are using opioids for nonobstetric chronic noncancer pain are lacking; thus, infant safety has not been established. Findings from the acute pain literature suggest that there are likely to be risks in breastfeeding mothers who are using opioids on a long-term basis. If long-term opioid use cannot be avoided in a breastfeeding mother, the risks may be minimized by providing safety instructions regarding monitoring for warning signs of toxic effects in infants. Among chronic pain clinic patients who are taking opioids, women are more likely than men to have polypharmacy.6 Such pharmaceutical complexity places women at greater risk than men for drug-drug interactions, additive adverse effects, and potential for poisoning or overdose. Rates of toxic reactions have tripled among women since 1999, and opioid-related poisoning hospitalizations have increased for women but not for men. Examples of factors related to poisoning could include overprescription, overuse by the patient, adverse effects, or toxic reactions related to drug-drug interactions. A study of unintentional pharmaceutical overdose fatalities reported that prescribed opioids were present in 44% of women.7 Drug monitoring program records showed that among fatality cases, women were more than twice as likely as men to have received prescriptions from 5 clinicians or more in the prior year.7 Therefore, women are at greater risk for polypharmacy, for unintentional poisoning death, and for receiving multiple opioid prescriptions from multiple providers. Psychosocial factors profoundly influence the experience of pain and coping with pain. Women are more likely than men to have depression and anxiety, 2 factors that strongly predict the receipt of opioids. Interpersonal factors are emerging as influential for opioid prescription and level of use. For instance, women with solicitous spouses are more likely to use greater amounts of opioids; the same is not true for men with solicitous spouses. Physician prescribing patterns have been linked to patients’ in-office display of pain behaviors,8 but data do not suggest sex differences. Finally, women are significantly more likely than men to endorse having poor capacity to set limits with others, and they are also more likely to report that their fear of disappointing others leads them to make poor decisions about their pain care. For instance, women are much more likely than men to exhibit poor pacing and to push themselves into greater pain severity in an effort to maintain their role in the family. Furthermore, women are more likely than men to endorse a lenient attitude toward taking pain medication to treat the consequences of poor pacing and poor self-care.9 Among persons seeking treatment for opioid abuse, women are more likely than men to report having received their opioids in the form of a legitimate prescription.10 As such, physicians may have a greater opportunity to prevent the misuse of opioids by women. Sex-specific risks include endocrinopathy, infertility, polypharmacy, unintentional poisoning, and abuse; these factors should influence decision making regarding initiating or continuing opioid therapy. Sex-specific monitoring in women who are taking opioids includes ongoing assessment for pregnancy plans, endocrinopathy, physician shopping, and the use of opioids to medicate psychosocial factors. Before initiating opioid treatment for chronic pain, in women or men, prescribers should fully assess the individual risks and benefits of the therapy and have a thorough discussion of the goals, risks, and consequences of such therapy with each patient.

To evaluate the use and direct medical costs of pharmacologic and alternative treatments for patients with osteoarthritis (OA) and chronic low back pain (CLBP).The LifeLink™ Health Plan Claims Database was used to identify patients ≥18 years old, diagnosed with OA (N = 112,951) or CLBP (N = 101,294). Of these patients, 64,085 with OA and 47,386 with CLBP received pain-related treatments during CY2008 and were selected for inclusion. For patients in both cohorts, pharmacologic and alternative treatments, and direct medical costs were examined during CY2008.Opioids were the most frequently prescribed medication (70%) in both groups, followed by nonselective nonsteroidal anti-inflammatory drugs (50%). Over 30% received antidepressants,20% received benzodiazepines, and 15% in each group received sedative hypnotics. Use of alternative treatments was as follows: chiropractor, OA 11%, CLBP 34%; physical therapy, 20% in both groups; transcutaneous electrical nerve stimulations (TENS), OA 14%, CLBP 22%; acupuncture, hydrotherapy, massage therapy, and biofeedback,3% in both groups. Mean (SD) total healthcare costs among these patients were, OA: $15,638 ($22,595); CLBP: $11,829 ($20,035). Pharmacologic therapies accounted for approximately 20% of these costs, whereas alternative treatments accounted for only 3% to 4% of the total costs.Patients with OA and CLBP used a variety of pain-related and adjunctive medications. Although, alternative treatments are widely recommended, we found limited use of several of these in clinical practice, potentially due to the source of our data (commercial claims). Further research is needed to ascertain the extent to which such therapies contribute to the total costs of OA and CLBP management.

T he diagnosis and treatment of chronic pain patients from the perspective of the traditional medical model often results in considerable confusion and frustration for all involved. Management of the individual patient with this approach has focused on the clinical history and physical findings, and the correlation of these findings with diagnostic tests. It is assumed that the data obtained from the interview, examination, and laboratory procedures provide reliable measures that permit valid diagnostic and prognostic interpretations. Difficulties in determining and measuring the medical and physical signs and symptoms that may be related to patients' reports of pain are well recognized, and as yet there are no widely accepted criteria for scoring the presence, absence, extent, or importance of particular biomedical f indings or diagnostic procedures. 6 To complicate matters further, physicians, at least in the United States, are being requested to integrate vague and often unreliable information not only to make diagnostic decisions, but also to make disability determinations and prognostic predictions. Stieg has succinctly argued that, at least as currently operationalized, biomedical and physical findings are not up to the task of accurately predicting disability and, we would add, treatment outcomes. To oversimplify, he asserts that disability is a legal rather than a medical issue and, whatever the illusive construct of disability involves, it cannot be measured or predicted by focusing on physical findings. Additionally, he suggests that existing research does

Retrospective analysis of an insurance claims database.To examine the comorbidities, treatment patterns, health care resource utilization, and direct medical costs of patients with chronic low back pain (CLBP) in clinical practice.Although the socioeconomic impact of CLBP is substantial, characterization of comorbidities, pain-related pharmacotherapy, and health care resource use/costs of patients with CLBP relative to non-CLBP controls have been infrequently documented.Using the LifeLink Health Plan Claims Database (IMS Health Inc., Watertown, MA), patients with CLBP, defined using the International Classification of Diseases, Ninth Revision, Clinical Modification, were identified and matched (age, sex, and region) with non-CLBP individuals. Comorbidities, pain-related pharmacotherapy, and health care service use/costs (pharmacy, outpatient, inpatient, total) were compared for the 2 groups during 2008.A total of 101,294 patients with CLBP and controls were identified (55% women; mean age was 47.2 ± 11.6 years). Relative to controls, patients with CLBP had a greater comorbidity burden including a significantly higher (P0.0001) frequency of musculoskeletal and neuropathic pain conditions and common sequelae of pain such as depression (13.0% vs. 6.1%), anxiety (8.0% vs. 3.4%), and sleep disorders (10.0% vs. 3.4%). Pain-related pharmacotherapy was significantly greater (P0.0001) among patients with CLBP including opioids (37.0% vs. 14.8%; P0.0001), nonsteroidal anti-inflammatory drugs (26.2% vs. 9.6%; P0.0001), and tramadol (8.2% vs. 1.2%; P0.0001). Prescribing of "adjunctive" medications for treating conditions associated with pain (i.e., depression, anxiety, and insomnia) was also significantly greater (P0.0001) among patients with CLBP; 36.3% of patients received combination therapy. Health care costs were significantly higher in the CLBP cohort (P0.0001), reflecting greater resource utilization. Total direct medical costs were estimated at $8386 ± $17,507 in the CLBP group and $3607 ± $10,845 in the control group; P0.0001).Patients with CLBP are characterized by greater comorbidity and economic burdens compared with those without CLBP. This economic burden can be attributed to greater prescribing of pain-related medications and increased health resource utilization.

Background The purpose of this study was to compare pre- and post-surgical healthcare costs in commercially insured total joint arthroplasty (TJA) patients with osteoarthritis (OA) in the United States (U.S.). Methods Using a large healthcare claims database, we identified patients over age 39 with hip or knee OA who underwent unilateral primary TJA (hip or knee) between 1/1/2006 and 9/30/2007. Utilization of healthcare services and costs were aggregated into three periods: 12 months "pre-surgery," 91 days "peri-operative," and 3 to 15 month "follow-up," Mean total pre-surgery costs were compared with follow-up costs using Wilcoxon signed-rank test. Results 14,912 patients met inclusion criteria for the study. The mean total number of outpatient visits declined from pre-surgery to follow-up (18.0 visits vs 17.1), while the percentage of patients hospitalized increased (from 7.5% to 9.8%) (both p < 0.01). Mean total costs during the follow-up period were 18% higher than during pre-surgery ($11,043 vs. $9,632, p < 0.01), largely due to an increase in the costs of inpatient care associated with hospital readmissions ($3,300 vs. $1,817, p < 0.01). Pharmacotherapy costs were similar for both periods ($2013 [follow-up] vs. $1922 [pre-surgery], p = 0.33); outpatient care costs were slightly lower in the follow-up period ($4338 vs. $4571, p < 0.01). Mean total costs for the peri-operative period were $36,553. Conclusions Mean total utilization of outpatient healthcare services declined slightly in the first year following TJA (exclusive of the peri-operative period), while mean total healthcare costs increased during the same time period, largely due to increased costs associated with hospital readmissions. Further study is necessary to determine whether healthcare costs decrease in subsequent years.

A number of pharmacologic treatments examined in recent randomized clinical trials (RCTs) have failed to show statistically significant superiority to placebo in conditions in which their efficacy had previously been demonstrated. Assuming the validity of previous evidence of efficacy and the comparability of the patients and outcome measures in these studies, such results may be a consequence of limitations in the ability of these RCTs to demonstrate the benefits of efficacious analgesic treatments vs placebo ("assay sensitivity"). Efforts to improve the assay sensitivity of analgesic trials could reduce the rate of falsely negative trials of efficacious medications and improve the efficiency of analgesic drug development. Therefore, an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials consensus meeting was convened in which the assay sensitivity of chronic pain trials was reviewed and discussed. On the basis of this meeting and subsequent discussions, the authors recommend consideration of a number of patient, study design, study site, and outcome measurement factors that have the potential to affect the assay sensitivity of RCTs of chronic pain treatments. Increased attention to and research on methodological aspects of clinical trials and their relationships with assay sensitivity have the potential to provide the foundation for an evidence-based approach to the design of analgesic clinical trials and expedite the identification of analgesic treatments with improved efficacy and safety.

Pregabalin is a ligand for the alpha-2-delta subunit of voltage-gated calcium channels with anticonvulsant, analgesic, and anxiolytic properties. It has predictable absorption across the gastrointestinal tract, is neither metabolized nor protein-bound, and has minimal drug-drug interactions. It is effective with two or three-times daily dosing in a dose range of 150 to 600 mg daily. Seven published prospective, randomized clinical trials in postherpetic neuralgia (PHN) and painful diabetic peripheral neuropathy (DPN) demonstrate pain relief, decreased sleep interference, and improvements in several secondary outcome measures. The 50% responder rates for PHN and DPN compare favorably with other first-line agents for neuropathic pain. Pregabalin is well tolerated in most patients with infrequent severe adverse effects. Pregabalin is an important addition to the treatment armamentarium for neuropathic pain.

A consensus meeting was convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to provide recommendations for interpreting clinical importance of treatment outcomes in clinical trials of the efficacy and effectiveness of chronic pain treatments. A group of 40 participants from universities, governmental agencies, a patient self-help organization, and the pharmaceutical industry considered methodologic issues and research results relevant to determining the clinical importance of changes in the specific outcome measures previously recommended by IMMPACT for 4 core chronic pain outcome domains: (1) Pain intensity, assessed by a 0 to 10 numerical rating scale; (2) physical functioning, assessed by the Multidimensional Pain Inventory and Brief Pain Inventory interference scales; (3) emotional functioning, assessed by the Beck Depression Inventory and Profile of Mood States; and (4) participant ratings of overall improvement, assessed by the Patient Global Impression of Change scale. It is recommended that 2 or more different methods be used to evaluate the clinical importance of improvement or worsening for chronic pain clinical trial outcome measures. Provisional benchmarks for identifying clinically important changes in specific outcome measures that can be used for outcome studies of treatments for chronic pain are proposed. Perspective Systematically collecting and reporting the recommended information needed to evaluate the clinical importance of treatment outcomes of chronic pain clinical trials will allow additional validation of proposed benchmarks and provide more meaningful comparisons of chronic pain treatments.

Purpose To describe patterns of use of tricyclic antidepressants (TCAs) (eg, amitriptyline, nortriptyline) among older patients with diabetic peripheral neuropathy (DPN). Materials and methods Using a large, integrated, US health-insurance claims database, we identified all patients who received TCAs between January 1, 1999 and June 30, 2001 ("study period"). Among these persons, we then selected those who: (1) were aged >or=65 years as of the date of first receipt of a TCA during the study period; and (2) had one or more healthcare encounters with a diagnosis of DPN in the 30-day period immediately preceding date of first receipt of a TCA. We then examined the prevalence of selected comorbidities and concurrent use of medications which might render inappropriate the prescribing of TCAs, based on a listing of contraindications, warnings, and precautions found in the package inserts for these medications. Patterns of TCA prescribing were examined, based on information on paid claims. Results There were 349 DPN patients, aged >or=65 years, who received TCAs. Mean age was 73.8 years, 55.9% were women, and 17.9% had diagnoses of depression. Most patients (84.0%) began therapy with amitriptyline. Almost one-half of study patients had indicators of potentially inappropriate TCA use, primarily cardiovascular comorbidities. Mean TCA dose among patients with and without these indicators was 23.3 (+/-13.4) mg and 25.4 (+/-15.3) mg, respectively (P=0.42). Conclusions The high prevalence of contraindications, warnings, or precautions and the low level of TCA exposure suggest that many older patients with DPN who receive TCAs may be inappropriately treated.