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Showing papers in "Pain Medicine in 2013"


Journal ArticleDOI
TL;DR: The fourth edition of diagnostic and treatment guidelines for complex regional pain syndrome (CRPS; aka reflex sympathetic dystrophy) is presented in this paper, where expert practitioners in each discipline traditionally utilized in the treatment of CRPS systematically reviewed the available and relevant literature; due to the paucity of levels 1 and 2 studies, less rigorous, preliminary research reports were included.
Abstract: Objective This is the fourth edition of diagnostic and treatment guidelines for complex regional pain syndrome (CRPS; aka reflex sympathetic dystrophy). Methods Expert practitioners in each discipline traditionally utilized in the treatment of CRPS systematically reviewed the available and relevant literature; due to the paucity of levels 1 and 2 studies, less rigorous, preliminary research reports were included. The literature review was supplemented with knowledge gained from extensive empirical clinical experience, particularly in areas where high-quality evidence to guide therapy is lacking. Results The research quality, clinical relevance, and “state of the art” of diagnostic criteria or treatment modalities are discussed, sometimes in considerable detail with an eye to the expert practitioner in each therapeutic area. Levels of evidence are mentioned when available, so that the practitioner can better assess and analyze the modality under discussion, and if desired, to personally consider the citations. Tables provide details on characteristics of studies in different subject domains described in the literature. Conclusions In the humanitarian spirit of making the most of all current thinking in the area, balanced by a careful case-by-case analysis of the risk/cost vs benefit analysis, the authors offer these “practical” guidelines.

408 citations


Journal ArticleDOI
TL;DR: In this article, the authors developed core competencies in pain assessment and management for pre-licensure health professional education, which can serve as a foundation for developing and defining curricula and as a resource for the creation of learning activities across health professions designed to advance care that effectively responds to pain.
Abstract: Objective: The objective of this project was to develop core competencies in pain assessment and management for prelicensure health professional education. Such core pain competencies common to all prelicensure health professionals have not been previously reported. Methods: An interprofessional executive committee led a consensus-building process to develop the core competencies. An in-depth literature review was conducted followed by engagement of an interprofessional Competency Advisory Committee to critique competencies through an iterative process. A 2-day summit was held so that consensus could be reached. Results: The consensus-derived competencies were categorized within four domains: multidimensional nature of pain, pain assessment and measurement, management of pain, and context of pain management. These domains address the fundamental concepts and complexity of pain; how pain is observed and assessed; collaborative approaches to treatment options; and application of competencies across the life span in the context of various settings, populations, and care team models. A set of values and guiding principles are embedded within each domain. Conclusions: These competencies can serve as a foundation for developing, defining, and revising curricula and as a resource for the creation of learning activities across health professions designed to advance care that effectively responds to pain

246 citations


Journal ArticleDOI
TL;DR: Findings suggest that MBIs decrease the intensity of pain for chronic pain patients, and implications for understanding mechanisms of change are discussed.
Abstract: Background Mindfulness-based interventions (MBIs) emphasizing a nonjudgmental attitude toward present moment experience are widely used for chronic pain patients. Although changing or controlling pain is not an explicit aim of MBIs, recent experimental studies suggest that mindfulness practice may lead to changes in pain tolerance and pain intensity ratings. Objective The objective of this review is to investigate the specific effect of MBIs on pain intensity. Methods A literature search was conducted using the databases PUBMED and PsycINFO for relevant articles published from 1960 to December 2010. We additionally conducted a manual search of references from the retrieved articles. Only studies providing detailed results on change in pain intensity ratings were included. Results Sixteen studies were included in this review (eight uncontrolled and eight controlled trials). In most studies (10 of 16), there was significantly decreased pain intensity in the MBI group. Findings were more consistently positive for samples limited to clinical pain (9 of 11). In addition, most controlled trials (6 of 8) reveal higher reductions in pain intensity for MBIs compared with control groups. Results from follow-up assessments reveal that reductions in pain intensity were generally well maintained. Conclusions Findings suggest that MBIs decrease the intensity of pain for chronic pain patients. We discuss implications for understanding mechanisms of change in MBIs.

189 citations


Journal ArticleDOI
TL;DR: In a substantial proportion of patients with lumbar radicular pain caused by contained disc herniations, lumbr transforaminal injection of corticosteroids is effective in reducing pain, restoring function, reducing the need for other health care, and avoiding surgery.
Abstract: Objective To determine the effectiveness of lumbar transforaminal injection of steroids in the treatment of radicular pain. Design Comprehensive review of the literature with systematic analysis of all published data. Interventions Four reviewers independently assessed 39 publications on the effectiveness of lumbar transforaminal injection of steroids. Each reviewer determined if a publication provided any valid information on effectiveness. Assessments were compared, and the data of each publication were evaluated in terms of the rigor with which they were produced and the evidence they provided of effectiveness. Outcome Measures The primary outcome sought was the success rate for relief of pain. Improvement in secondary outcomes was noted if reported. Results For miscellaneous conditions, the available evidence is limited and is neither compelling nor conclusive. For disc herniation, the evidence is sufficiently abundant to show that lumbar transforaminal injection of steroids is not universally effective but, nevertheless, benefits a substantial proportion of patients, and is not a placebo. Success rates are higher in patients with contained herniations that cause only low-grade compression of the nerve. Conclusion In a substantial proportion of patients with lumbar radicular pain caused by contained disc herniations, lumbar transforaminal injection of corticosteroids is effective in reducing pain, restoring function, reducing the need for other health care, and avoiding surgery. The evidence supporting this conclusion was revealed by comprehensive review of all published data and found to be much more compelling than it would have been if the literature review had been of the limited scope of a traditional “systematic review” of randomized, controlled trials only.

182 citations


Journal ArticleDOI
TL;DR: In this article, the authors developed the Defense and Veterans Pain Rating Scale (DVPRS) to improve interpretability of incremental pain intensity levels, and to improve communication and documentation across all transitions of care.
Abstract: Background. The Army Surgeon General released the Pain Management Task Force final report in May 2010. Among military providers, concerns were raised that the standard numeric rating scale (NRS) for pain was inconsistently administered and of questionable clinical value. In response, the Defense and Veterans Pain Rating Scale (DVPRS) was developed. Methods. The instrument design integrates pain rating scale features to improve interpretability of incremental pain intensity levels, and to improve communication and documentation across all transitions of care. A convenience sample of 350 inpatient and outpatient active duty or retired military service members participated in the study at Walter Reed Army Medical Center. Participants completed the five-item DVPRS—one pain intensity NRS with and without word descriptors presented in random order and four supplemental items measuring general activity, sleep, mood, and level of stress and the Brief Pain Inventory seven interference items. Using systematic sampling, a random sample was selected for a word descriptor validation procedure matching word phases to corresponding pain intensity on the NRS. Results. Parallel forms reliability and concurrent validity testing demonstrated a robust correlation. When the DVPRS was presented with the word descriptors first, the correlation between the two ratings was slightly higher, r = 0.929 (N = 171; P < 0.001), than ordering first without the descriptors, r = 0.882 (N = 177; P < 0.001). Intraclass correlation coefficient was 0.943 showing excellent alignment of word descriptors by respondents (N = 42), matching them correctly with pain level. Conclusions. The DVPRS tool demonstrated acceptable psychometric properties in a military population.

142 citations


Journal ArticleDOI
TL;DR: It is imperative that clinicians encourage older people with chronic pain to remain active as physical activity is a central non-pharmacological strategy in the management of chronic pain and is integral for healthy aging.
Abstract: Objective: To compare the overall levels of physical activity of older adults with chronic musculoskeletal pain and asymptomatic controls. Review Methods: A systematic review of the literature was conducted using a Cochrane methodology and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Major electronic databases were searched from inception until December 2012, including the Cochrane Library, CINAHL, EBSCO, EMBASE, Medline, PubMed, PsycINFO, and the international prospective register of systematic reviews. In addition, citation chasing was undertaken, and key authors were contacted. Eligibility criteria were established around participants used and outcome measures focusing on daily physical activity. A meta-analysis was conducted on appropriate studies. Results: Eight studies met the eligibility criteria, four of these reported a statistically lower level of physical activity in the older adult sampl e with chronic pain compared with the asymptomatic group. It was possible to perform a non-heterogeneous meta-analysis on five studies. This established that 1,159 older adults with chronic pain had a significantly lower level of physical activity (−0.20, confidence interval 95% = −0.34 to −0.06, p = 0.004) compared with 576 without chronic pain. Conclusion: Older adults with chronic pain appear to be less active than asymptomatic controls. Although this difference was small, it is likely to be clinically meaningful. It is imperative that clinicians encourage older people with chronic pain to remain active as physical activity is a central non-pharmacological strategy in the management of chronic pain and is integral for healthy aging. Future research should prioritize the use of objective measurement of physical activity.

139 citations


Journal ArticleDOI
TL;DR: SCS with CMM is cost-effective compared with C MM alone in the management of FBSS, CRPS, PAD, and RAP and generates a positive INMB for treatment of pain syndromes.
Abstract: Objective. To evaluate the cost-effectiveness of spinal cord stimulation (SCS) and conventional medical management (CMM) compared with CMM alone for patients with failed back surgery syndrome (FBSS), complex regional pain syndrome (CRPS), peripheral arterial disease (PAD), and refractory angina pectoris (RAP). Design. Markov models were developed to evaluate the cost-effectiveness of SCS vs CMM alone from

134 citations


Journal ArticleDOI
TL;DR: Evidence suggests that CPN should be considered in patients with upper abdominal cancer where the pain is not adequately controlled with systemic analgesics or when significant opioid-induced side effects are present, and robust evidence for EUS CPN is lacking.
Abstract: Objective This systematic review assesses the effectiveness and side effects of celiac plexus neurolysis (CPN) in the treatment of upper abdominal cancer pain, and evaluates whether there are any differences between the percutaneous and endoscopic ultrasound-guided (EUS) denervation techniques. Methods Five databases were searched, expanded by assessing the reference lists of all retrieved papers. Sixty-six publications fulfilled the inclusion/exclusion criteria and were included in the systematic review. Randomized controlled trials were available for the percutaneous CPN, and therefore meta-analyses were performed for pain, opioid consumption, and specific side effects. The quality of life data were too heterogeneous to be assessed by a meta-analysis, and evidence for EUS CPN could only be evaluated by observational studies. Results Meta-analyses show that percutaneous CPN significantly improves pain in patients with upper abdominal cancer, with a decrease in opioid consumption and side effects. It is unclear whether there is any change in quality of life. Case series suggest that EUS CPN improves pain. No conclusion can be made about EUS CPN's influence on opioid consumption. Although CPN is a safe procedure, side effects and complications can occur with both the percutaneous and EUS techniques. Conclusions Following this review, evidence suggests that CPN should be considered in patients with upper abdominal cancer where the pain is not adequately controlled with systemic analgesics or when significant opioid-induced side effects are present. The percutaneous approach remains the standard technique as robust evidence for EUS CPN is lacking.

123 citations


Journal ArticleDOI
TL;DR: All of the null hypotheses that have been raised against the concept of discogenic pain and its diagnosis have each been refuted by one or more studies.
Abstract: Objective To test the null hypotheses that: lumbar intervertebral discs cannot be a source of pain; discs are not a source of pain; painful lumbar discs cannot be diagnosed; and there is no pathology that causes discogenic pain. Methods Philosophical essay and discourse with reference to the literature. Results Anatomic and physiologic evidence denies the proposition that disc cannot be a source of pain. In patients with back pain, discs can be source of pain. No studies have refuted the ability of disc stimulation to diagnose discogenic pain. Studies warn only that disc stimulation may have a false-positive rate of 10% or less. Internal disc disruption is the leading cause of discogenic pain. Discogenic pain correlates with altered morphology on computerized tomography scan, with changes on magnetic resonance imaging, and with internal biophysical features of the disc. The morphological and biophysical features of discogenic pain have been produced in biomechanics studies and in laboratory animals. Conclusions All of the null hypotheses that have been raised against the concept of discogenic pain and its diagnosis have each been refuted by one or more studies. Although studies have raised concerns, none has sustained any null hypothesis. Discogenic pain can occur and can be diagnosed if strict operational criteria are used to reduce the likelihood of false-positive results.

114 citations


Journal ArticleDOI
TL;DR: This retrospective observational study reveals no evidence that dexamethasone is less effective than particulate steroids in lumbar TFESIs performed for radicular pain with or without radiculopathy.
Abstract: Objective To assess whether a nonparticulate steroid (dexamethasone, 10 mg) is less clinically effective than the particulate steroids (triamcinolone, 80 mg; betamethasone, 12 mg) in lumbar transforaminal epidural steroid injections (TFESIs) in subjects with radicular pain with or without radiculopathy. Design Retrospective observational study with noninferiority analysis of dexamethasone relative to particulate steroids. Setting Single academic radiology pain management practice. Subjects Three thousand six hundred forty-five lumbar TFESIs at the L4-5, L5-S1, or S1 neural foramina, performed on 2,634 subjects. Methods/Outcome Measures Subjects were assessed with a pain numerical rating scale (NRS, 0–10) and Roland–Morris disability questionnaire (R-M) prior to TFESI, and at 2 weeks and 2 months follow-up. For categorical outcomes, successful pain relief was defined as either ≥50% reduction in NRS or pain 0/10; functional success was defined as ≥40% reduction in R-M score. Noninferiority analysis was performed with δ = −10% as the limit of noninferiority. Continuous outcomes (mean NRS, R-M scores) were analyzed for noninferiority with difference bounds of 0.3 for NRS scores and 1.0 for R-M scores. Results With categorical outcomes, dexamethasone was demonstrated to be noninferior to the particulate steroids in pain relief and functional improvement at 2 months. Using continuous outcomes, dexamethasone was demonstrated to be superior to the particulate steroids in both pain relief and functional improvement at 2 months. Conclusion This retrospective observational study reveals no evidence that dexamethasone is less effective than particulate steroids in lumbar TFESIs performed for radicular pain with or without radiculopathy.

112 citations


Journal ArticleDOI
TL;DR: The economic burden of opioid poisoning in the United States is quantified to help evaluate the economic case for efforts to reverse or prevent opioid poisoning and its associated morbidity and mortality.
Abstract: OBJECTIVE: To estimate the yearly economic burden of opioid-related poisoning in the United States. BACKGROUND: Rates of opioid poisoning and related mortality have increased substantially over the past decade. Although previous studies have measured the costs of misuse and abuse, costs related specifically to opioid poisoning have not been quantified. This study quantifies the economic burden of opioid poisoning in the United States to help evaluate the economic case for efforts to reverse or prevent opioid poisoning and its associated morbidity and mortality. METHODS: Mean costs and prevalence estimates were estimated using publically available datasets. A societal perspective was assumed and accordingly estimated direct medical and productivity costs. Direct medical costs included treatment for opioid poisoning in the emergency department (ED) and inpatient settings, along with emergency transport and drug costs. Productivity costs were estimated using the human capital method and included lost wages due to mortality and absenteeism costs from ED visits and hospitalizations. All costs were inflated to 2011 U.S. dollars. RESULTS: In 2009, total costs were estimated at approximately $20.4 billion with indirect costs constituting 89% of the total. Direct medical costs were approximately $2.2 billion. ED costs and inpatient costs were estimated to be $800 million and $1.3 billion, respectively. Absenteeism costs were $335 million and lost future earnings due to mortality were $18.2 billion. CONCLUSION: Opioid-related poisoning causes a substantial burden to the United States each year. Costs related to mortality account for the majority of costs. Interventions designed to prevent or reverse opioid-related poisoning can have significant impacts on cost, especially where death is prevented. Language: en

Journal ArticleDOI
TL;DR: Chronic back pain, mediated by the lumbar medial branches, can be stopped and patients fully restored to normal living, if treated with RFN, when performed in a rigorous manner in appropriately selected patients.
Abstract: Objective This study aims to determine the effectiveness of lumbar medial branch radiofrequency neurotomy (RFN) performed by two practitioners trained according to rigorous guidelines. Design Prospective, outcome study of consecutive patients with chronic back pain treated in a community setting. Interventions A total of 106 patients, selected on the basis of complete relief of pain following controlled, diagnostic, medial branch blocks, were treated with RFN according to the guidelines of the International Spine Intervention Society. Outcome Measures Successful outcome was defined as complete relief of pain for at least 6 months, with complete restoration of activities of daily living, no need for any further health care, and return to work. Patients who failed to meet any of these criteria were deemed to have failed treatment. Results In the two practices, 58% and 53% of patients achieved a successful outcome. Relief lasted 15 months from the first RFN and 13 months for repeat treatments. Allowing for repeat treatment, patients maintained relief for a median duration of 17–33 months, with some 70% still having relief at follow-up. Conclusion Lumbar RFN can be very effective when performed in a rigorous manner in appropriately selected patients. Chronic back pain, mediated by the lumbar medial branches, can be stopped and patients fully restored to normal living, if treated with RFN.

Journal ArticleDOI
TL;DR: This study provides a national overview of the prevalence, causes, severity, management and impact of chronic pain in Australian general practice patients, and the parity between GP and patient satisfaction with pain management.
Abstract: Objective To determine the prevalence of chronic pain, its causes, severity, management, impact on sleep, mood and activity levels, and general practitioner (GP) and patient satisfaction with pain management. Design A subset of 197 GPs and 5,793 patients from the BEACH program, a continuous, national cross-sectional survey of Australian general practice. Results The prevalence of chronic pain was 19.2% (95% confidence interval: 17.4–21.0) (N = 1,113). The most commonly reported causal conditions were osteoarthritis (48.1%) and back problems (29.4%). For pain severity (using Von Korff's pain grades), 25.2% were at Grade I (lowest); 37.1% were at Grade II; 28.3% at Grade III; and 9.4% at Grade IV (highest). Medication was used for pain management by 86.1% of patients, and one third also used nonpharmacological managements. One third of patients were taking opioids, most commonly those at the highest pain severity grades. On “Live Better with Pain Log” scale, the impact of pain was similar across activity (mean = 4.0), sleep (mean = 4.8), and mood (mean = 4.8). On a scale of 1 (highest) to 5 (lowest), GPs' satisfaction (mean = 2.5) was highly correlated (r = 0.7) with patients' satisfaction (mean = 2.6) with pain management. Conclusions Chronic pain impairs patient quality of life, and is a public health burden. This study provides a national overview of the prevalence, causes, severity, management and impact of chronic pain in Australian general practice patients, and the parity between GP and patient satisfaction with pain management.

Journal ArticleDOI
TL;DR: There is evidence that ketamine may be a viable option for treatment-refractory cancer pain, despite limitations in the breadth and depth of data available.
Abstract: Objective Chronic cancer pain is often refractory and difficult to treat. Ketamine is a medication with evidence of efficacy in the treatment of chronic pain. Design This article presents a synthesis of the data on ketamine for refractory cancer pain in adults and children. Results There are five randomized, double-blind, controlled trials of ketamine use in cancer pain that demonstrate improvement in pain for some patients. There are six prospective, uncontrolled trials in cancer pain that also demonstrate improvement in pain scores for some patients. There are no randomized, controlled trials in children with cancer pain, although there are a few studies reflecting improved pain control with ketamine for children with cancer pain. Adverse events for adults on ketamine are most commonly somnolence, feelings of insobriety, nausea/vomiting, hallucinations, depersonalization/derealization, and drowsiness. However, when ketamine is combined with benzodiazepines, feelings of insobriety, hallucinations, and depersonalization/derealization are not reported. Children on ketamine have had few reported adverse effects, which include sedation, anorexia, urinary retention, and myoclonic movements. Recommended ketamine infusion dosages are from 0.05 to 0.5 mg/kg/h (intravenous or subcutaneous). Recommended oral dosages of ketamine are 0.2–0.5 mg/kg/dose two to three times daily with a maximum of 50 mg/dose three times daily. Conclusions Despite limitations in the breadth and depth of data available, there is evidence that ketamine may be a viable option for treatment-refractory cancer pain.

Journal ArticleDOI
TL;DR: Patients classified by the SOAPP-SF in the current study as high risk tended to be younger, endorse more pain, have higher MEDD requirement, and endorse more symptoms of depression and anxiety, consistent with the literature on risk factors of opioid abuse in chronic pain patients.
Abstract: Background. Opioids are recognized as an integral part of the armamentarium in the management of cancer pain. There has been a growing awareness of the misuse of prescription opioids among cancer patients. More research is needed to detail risk factors and incidence for opioid misuse among cancer pain patients. Methods. We reviewed 522 patient charts that were seen in our Pain Center from January 1, 2009 to June 30, 2009 for risk stratification of opioid misuse with demographic and clinical factors utilizing the Screener and Opioid Assessment for Patients with Pain-short form (SOAPP-SF). Group differences based on High (≥4) and Low (<4) SOAPP-SF scores were evaluated at initial visit, follow-up within a month and 6–9 months. Results. One hundred forty-nine of the 522 (29%) patients had a SOAPP-SF score of ≥4. The mean age for patients with high SOAPP-SF score (≥4) was 50 ± 14 vs 56 ± 14 for patients with low SOAPP-SF score (<4) (P < 0.0001). The pain scores were higher for patients with high SOAPP-SF score compared with patients with low SOAPP-SF score at consult (P < 0.0001). Morphine equivalent daily dose (MEDD) was higher for patients with high SOAPP-SF score compared with patients with low SOAPP-SF score at consult (P = 0.0461). Fatigue, feeling of well-being, and poor appetite were higher among the high SOAPP-SF group at initial visit (P < 0.0001, <0.0001, <0.0149, respectively). The high SOAPP-SF score patients also had statistically significant (P < 0.05) higher anxiety and depression scores at all three time points. In the multivariate analysis, patients younger than 55 years have a higher odds of having a “high” SOAPP-SF score than patients 55 years and older {odds ratio (OR) (95% confidence interval [CI]) = 2.76 (1.58, 4.81), P = 0.0003} adjusting for employment status, disease status, treatment status, usual pain score, and morphine equivalency at consult. Patients with higher usual pain score at consult have higher odds of a “high” SOAPP-SF score (OR [95% CI] = 1.34 [1.19, 1.51], P < 0.0001) adjusting for age, employment status, disease status, treatment status, and morphine equivalency at consult. Conclusion. Patients classified by the SOAPP-SF in the current study as high risk tended to be younger, endorse more pain, have higher MEDD requirement, and endorse more symptoms of depression and anxiety. These findings are consistent with the literature on risk factors of opioid abuse in chronic pain patients which suggests that certain patient characteristics such as younger age, anxiety, and depression symptomatology are associated with greater risk for opioid misuse. However, a limitation of the current study is that other measures of opioid abuse were not available for validation and comparison with the SOAPP-SF.

Journal ArticleDOI
TL;DR: In this article, the authors identify unmet spiritual needs in patients with chronic pain diseases and cancer living in a secular society, and show that these needs can be predicted best by (religious) "trust", the illness interpretation "call for help", and living with a partner.
Abstract: Objective Research has shown that several patients report unmet psychosocial and spiritual needs. While most studies focus on patients with advanced stages of disease, we intended to identify unmet spiritual needs in patients with chronic pain diseases and cancer living in a secular society. Methods In an anonymous cross-sectional study, standardized questionnaires were provided to German patients with chronic pain diseases (and cancer), i.e., Spiritual Needs Questionnaire (SpNQ), Spirituality/Religiosity and Coping (SpREUK-15), Spiritual Well-being (FACIT-Sp), Brief Multidimensional Life Satisfaction Scale, Interpretation of Illness Questionnaire, and Escape from Illness (Escape). Results We enrolled 392 patients (67% women, mean age 56.3 ± 13.6 years; 61% Christian denomination) with chronic pain diseases (86%) and cancer (14%). Religious Needs (mean score 0.5 ± 0.8 on the scale) and Existential Needs (0.8 ± 0.8 on the scale) were low, while needs for Inner Peace (1.5 ± 0.9 on the scale) and Giving/Generativity were scored high (1.3 ± 1.0 on the scale). Regression analyses indicated that Religious Needs can be predicted best by (religious) “Trust,” the illness interpretation “call for help,” and living with a partner; Existential Needs can be predicted by “call for help” and to a weaker extent by (religious) “Trust.” Existential Needs are influenced negatively by the illness interpretation “challenge.” Needs for Inner Peace were predicted only in trend by the illness interpretation “threat,” and there were no significant predictors for the Giving/Generativity needs in the respective regression model. Conclusions Patients with chronic pain diseases predominantly report needs related to inner peace and generative relatedness on a personal level, whereas needs related to transcendent relatedness were of minor relevance. Nevertheless, even religious “skeptics” can express specific religious needs, and these should be recognized. Addressing patients' specific needs and also supporting them in their struggle with chronic illness remain a challenging task for the modern health care system.

Journal ArticleDOI
TL;DR: In this article, the authors used multimolecular immunocytochemistry to assess different types of cutaneous innervation in 3'mm skin biopsies from glabrous hypothenar and trapezius regions.
Abstract: Objective To determine if peripheral neuropathology exists among the innervation of cutaneous arterioles and arteriole–venule shunts (AVS) in fibromyalgia (FM) patients Setting Cutaneous arterioles and AVS receive a convergence of vasoconstrictive sympathetic innervation, and vasodilatory small-fiber sensory innervation Given our previous findings of peripheral pathologies in chronic pain conditions, we hypothesized that this vascular location may be a potential site of pathology and/or serotonergic and norepinephrine reuptake inhibitors (SNRI) drug action Subjects Twenty-four female FM patients and nine female healthy control subjects were enrolled for study, with 14 additional female control subjects included from previous studies AVS were identified in hypothenar skin biopsies from 18/24 FM patient and 14/23 control subjects Methods Multimolecular immunocytochemistry to assess different types of cutaneous innervation in 3 mm skin biopsies from glabrous hypothenar and trapezius regions Results AVS had significantly increased innervation among FM patients The excessive innervation consisted of a greater proportion of vasodilatory sensory fibers, compared with vasoconstrictive sympathetic fibers In contrast, sensory and sympathetic innervation to arterioles remained normal Importantly, the sensory fibers express α2C receptors, indicating that the sympathetic innervation exerts an inhibitory modulation of sensory activity Conclusions The excessive sensory innervation to the glabrous skin AVS is a likely source of severe pain and tenderness in the hands of FM patients Importantly, glabrous AVS regulate blood flow to the skin in humans for thermoregulation and to other tissues such as skeletal muscle during periods of increased metabolic demand Therefore, blood flow dysregulation as a result of excessive innervation to AVS would likely contribute to the widespread deep pain and fatigue of FM SNRI compounds may provide partial therapeutic benefit by enhancing the impact of sympathetically mediated inhibitory modulation of the excess sensory innervation

Journal ArticleDOI
TL;DR: A literature search on bibliographic resources, including EMBASE, PubMed Cochrane Database of Systemic Reviews from literature published from 1966 to December 1, 2012 to identify studies and treatments directed at the dorsal root ganglion (DRG) to treat chronic pain, and was limited to the English language Case series, case reports, and preclinical work were excluded Information on emerging technologies and pharmacologics were captured separately, as they did not meet the inclusion criteria as discussed by the authors.
Abstract: Objective The purpose of the study was to systematically review the historical therapeutics for chronic pain care directed at the dorsal root ganglion (DRG) and to identify future trends and upcoming treatment strategies Methods A literature search on bibliographic resources, including EMBASE, PubMed Cochrane Database of Systemic Reviews from literature published from 1966 to December 1, 2012 to identify studies and treatments directed at the DRG to treat chronic pain, and was limited to the English language Case series, case reports, and preclinical work were excluded Information on emerging technologies and pharmacologics were captured separately, as they did not meet the inclusion criteria Results The literature review yielded three current clinical treatment strategies: ganglionectomy, conventional radiofrequency treatment of the dorsal root ganglion, and pulsed radiofrequency treatment of the DRG Seven studies were identified utilizing ganglionectomy, 14 for conventional radiofrequency, and 16 for pulsed radiofrequency Electrical stimulation and novel therapeutic delivery strategies have been proposed and are in development Conclusions Despite a robust understanding of the DRG and its importance in acute nociception, as well as the development and maintenance of chronic pain, relatively poor evidence exists regarding current therapeutic strategies Novel therapies like electrical and pharmacologic strategies are on the horizon, and more prospective study is required to better qualify the role of the DRG in chronic pain care

Journal ArticleDOI
TL;DR: The small molecule AT₂R antagonist, EMA401, is in clinical development as a novel analgesic for the relief of neuropathic pain.
Abstract: Objective Neuropathic pain is an area of unmet clinical need. The objective of this study was to define the pharmacokinetics, oral bioavailability, and efficacy in rats of small molecule antagonists of the angiotensin II type 2 receptor (AT2R) for the relief of neuropathic pain. Design and Methods. Adult male Sprague-Dawley (SD) rats received single intravenous (110mg/kg) or oral (510mg/kg) bolus doses of EMA200, EMA300, EMA400 or EMA401 (S-enantiomer of EMA400). Blood samples were collected immediately pre-dose and at specified times over a 12- to 24-hour post-dosing period. Liquid chromatography tandem mass spectrometry was used to measure plasma drug concentrations. Efficacy was assessed in adult male SD rats with a unilateral chronic constriction injury (CCI) of the sciatic nerve. Results. After intravenous administration in rats, mean (+/- standard error of the mean) plasma clearance for EMA200, EMA300, EMA400, and EMA401 was 9.3, 6.1, 0.7, and 1.1L/hour/kg, respectively. After oral dosing, the dose-normalized systemic exposures of EMA400 and EMA401 were 20- to 30-fold and 50- to 60-fold higher than that for EMA300 and EMA200, respectively. The oral bioavailability of EMA400 and EMA401 was similar at approximate to 30%, whereas it was only 5.9% and 7.1% for EMA200 and EMA300, respectively. In CCI rats, single intraperitoneal bolus doses of EMA200, EMA300, and EMA400 evoked dose-dependent pain relief. The pain relief potency rank order in CCI rats was EMA400>EMA300>EMA200 in agreement with the dose-normalized systemic exposure rank order in SD rats. Conclusion. The small molecule AT2R antagonist, EMA401, is in clinical development as a novel analgesic for the relief of neuropathic pain.

Journal ArticleDOI
TL;DR: This novel system, combining biofeedback and virtual reality, is feasible for pediatric use and Randomized controlled studies in larger populations are needed in order to determine the utility of the system in reducing headache, improving daily functioning, and elevating quality of life.
Abstract: Objective Pediatric headache is highly widespread and is associated with distress and reduced quality of life. Pharmacological treatment of chronic headache in children has been only partially effective and, as in medication-overuse headache, can sometimes be counterproductive. Therefore, there is a substantial need to develop other effective methods of treatment. Here we present the rationale, feasibility, and preliminary results of a pilot study applying a novel system, combining virtual reality and biofeedback, aimed as an abortive treatment of pediatric chronic headache. Design A prospective single-arm open-label, pilot study. Ten children attending an outpatient pediatric neurology clinic were treated by the proposed system. Participants practiced relaxation with biofeedback and learned to associate successful relaxation with positive pain-free virtual images of themselves. Results Nine patients completed the 10-session intervention. Ratings of pain, daily functioning, and quality of life improved significantly at 1 and at 3 months posttreatment. Most patients reported applying their newly acquired relaxation and imagery skills to relieve headache outside the lab. Conclusion This novel system, combining biofeedback and virtual reality, is feasible for pediatric use. Randomized controlled studies in larger populations are needed in order to determine the utility of the system in reducing headache, improving daily functioning, and elevating quality of life.

Journal ArticleDOI
TL;DR: Topical NSAIDs have been shown to be beneficial from both a therapeutics and adverse effect perspective, and are increasingly recommended in treatment guidelines.
Abstract: Objective This article reviews topical nonsteroidal anti-inflammatory drug (NSAID) formulations available in the United States, including advantages and disadvantages, therapeutic usefulness, adverse effects, and formulation considerations. Results In the United States, several topical NSAID products are approved to treat painful conditions including diclofenac sodium 1% gel (Voltaren Gel®; Endo Pharmaceuticals), diclofenac sodium topical solution 1.5% w/w in 45.5% dimethyl sulfoxide (PENNSAID®; Mallinckrodt, Inc.), and diclofenac epolamine 1.3% (Flector Patch®; Alpharma Pharmaceuticals LLC, a subsidiary of Pfizer, Inc.). Recent studies suggest topical diclofenac preparations are effective for osteoarthritis pain and suggest the efficacy of topical formulations is similar to that achieved with oral NSAID formulations. All NSAID formulations contain the same boxed warnings regarding cardiovascular and renal toxicity; however, topical NSAIDs are proposed to have a more favorable safety profile than oral NSAIDs due to the low serum concentrations achieved with topical NSAID formulations. Conclusions Topical NSAIDs have been shown to be beneficial from both a therapeutics and adverse effect perspective, and are increasingly recommended in treatment guidelines.

Journal ArticleDOI
TL;DR: It is suggested that CPM paradigms possess sufficient reliability to be incorporated into bedside clinical evaluation of patients with chronic pain, but only among women, and the lack of CPM reproducibility/stability observed among men places limits on the potential use of C PM paradigm in clinical settings for the assessment of men's endogenous pain-inhibitory function.
Abstract: Objectives To examine the temporal stability of conditioned pain modulation (CPM), formerly termed diffuse noxious inhibitory controls, among a sample of patients with chronic pain. The study also examined the factors that might be responsible for the stability of CPM. Design, Subjects, and Methods In this test-retest study, patients underwent a series of standardized psychophysical pain-testing procedures designed to assess CPM on two separate occasions (i.e., baseline and follow up). Patients also completed self-report measures of catastrophizing (Pain Catastrophizing Scale [PCS] and negative affect [NA]). Results Overall, results provided evidence for the stability of CPM among patients with chronic pain. Results, however, revealed considerable sex differences in the stability of CPM. For women, results revealed a significant test-retest correlation between baseline and follow-up CPM scores. For men, however, the test-retest correlation between baseline and follow-up CPM scores was not significant. Results of a Fisher's Z-test revealed that the stability of CPM was significantly greater for women than for men. Follow-up analyses revealed that the difference between men and women in the stability of CPM could not be accounted for by any demographic (e.g., age) and/or psychological factors (PCS and NA). Conclusions Our findings suggest that CPM paradigms possess sufficient reliability to be incorporated into bedside clinical evaluation of patients with chronic pain, but only among women. The lack of CPM reproducibility/stability observed among men places limits on the potential use of CPM paradigms in clinical settings for the assessment of men's endogenous pain-inhibitory function.

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TL;DR: Competing demands of primary care practice, differing beliefs about pain, and uncertainties about the appropriate place of opioid therapy in chronic pain management likely contributed to the identified tensions.
Abstract: Objective With greater scrutiny on primary care providers' (PCPs) approaches to chronic pain management, more research is needed to clarify how concerns and uncertainties about opioid therapy affect the ways both patients with chronic pain and PCPs experience primary care interactions. The goal of this qualitative study was to develop a better understanding of the respective experiences, perceptions, and challenges that patients with chronic pain and PCPs face communicating with each other about pain management. Design Purposive and snowball sampling techniques were used to identify 14 PCPs. Patients who received ≥6 opioid prescriptions during the prior year were selected at random from the panels of participating physicians. Face-to-face in-depth interviews were conducted individually with patients and PCPs. Setting VISN 11 Roudebush VA Medical Center (RVAMC) in Indianapolis, Indiana. Subjects Fourteen PCPs and 26 patients with chronic pain participated. Methods An inductive thematic analysis was conducted separately with patient and PCP interview data, after which the emergent themes for both groups were compared and contrasted. Results Three notable tensions between patients and PCPs were discovered: 1) the role of discussing pain versus other primary care concerns, 2) acknowledgment of pain and the search for objective evidence, and 3) recognition of patient individuality and consideration of relationship history. Conclusions Competing demands of primary care practice, differing beliefs about pain, and uncertainties about the appropriate place of opioid therapy in chronic pain management likely contributed to the identified tensions. Several clinical communication strategies to help PCPs mitigate and manage pain-related tensions are discussed.

Journal ArticleDOI
TL;DR: The Turkish version of the PD-Q is a reliable and valid scale to be used to determine neuropathic component of chronic pain in Turkish patients.
Abstract: Objectives The aim of this study was to develop a Turkish version of the painDETECT questionnaire (PD-Q) and assess its reliability and validity. Methods Two hundred and forty patients who were diagnosed by expert pain physicians in daily clinical practice and classified as having either neuropathic, nociceptive, or mixed pain for at least 3 months were enrolled in this study. After the usual translation process, the Turkish version of the PD-Q was administered to each participant twice with an interval of 48 hours. The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), Douleur Neuropathique en 4 questions (DN4) and a pain visual analog scale were assessed along with the PD-Q. Chronbach's α was calculated to evaluate internal consistency of the PD-Q. Intraclass correlation coefficient was calculated to examine test-retest reliability. Convergent validity was assessed by correlating the scale with LANSS and DN4. Discriminant statistics—sensitivity, specificity, Youden index, positive predictive value, negative predictive value—were also assessed. Results A total of 240 patients with chronic pain, 80 patients in each neuropathic, nociceptive, and mixed pain group, were included in this study. Mean age of the patients was 54.1 years, and majority of the patients were female (52.9%). Chronbach's α of the Turkish version of the PD-Q was 0.81. The test-retest reliability of the Turkish version of the PD-Q was determined as 0.98 for the total score and ranged from 0.86 to 0.99 for individual items. The Turkish version of the PD-Q was possitively and significantly corralated with LANSS (r 0.89, P < 0.001) and DN4 (r 0.82, P < 0.001). When the two cutoff values in the original version were used, sensitivity was found 77.5% for a cutoff value ≤19, and specificity was 82.5%. Sensitivity and specificity were 90% and 67.5%, respectively, for the other cutoff value ≤12. Scores ≤12 represents a negative predictive value = 87%, and scores 19≤ represents a positive predictive value = 82%. When mixed pain patients were included in the neuropathic pain group, discriminant values were reduced as expected. Conclusions The Turkish version of the PD-Q is a reliable and valid scale to be used to determine neuropathic component of chronic pain in Turkish patients.

Journal ArticleDOI
TL;DR: The clinical benefits observed in this study are the result of non-placebo treatment effects afforded by IDB, which should be recommended to select the patients with chronic discogenic low back pain.
Abstract: Objective The aim was to compare the efficacy of intradiscal biacuplasty (IDB) with that of placebo treatment for discogenic low back pain. Design This is a randomized, placebo-controlled trial. Subjects were randomized on a 1:1 basis to IDB and sham groups. Follow-ups were conducted at 1, 3, and 6 months. Subjects and coordinators were blinded to randomization until 6 months. Of the 1,894 subjects screened, 64 subjects were enrolled, and 59 were treated: 29 randomized to IDB and 30 to sham. All subjects had a history of chronic low back pain for longer than 6 months. Interventions Two cooled radiofrequency (RF) electrodes placed in a bipolar manner in affected discs to lesion the nociceptive fibers of the annulus fibrosus. The sham procedure was identical to the active treatment except that probes were not directly inserted into the disc space, and RF energy was not actively delivered. Results The principal outcome measures were physical function, pain, disability, and opioid usage. Patients in the IDB group exhibited statistically significant improvements in physical function ( P = 0.029), pain ( P = 0.006), and disability ( P = 0.037) at 6-month follow-up as compared to patients who received sham treatment. Treatment patients reported a reduction of 16 mg daily intake of opioids at 6 months; however, the results were not statistically different from sham patients. Conclusions The results suggest that the clinical benefits observed in this study are the result of non-placebo treatment effects afforded by IDB. IDB should be recommended to select the patients with chronic discogenic low back pain. (Clinicaltrials.gov number, [NCT00750191][1].) [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00750191&atom=%2Fpainmedicine%2F14%2F3%2F362.atom

Journal ArticleDOI
TL;DR: Investigating the relationship of pain to functional impairment in HIV-infected patients, independent of mood disorders and substance abuse found pain was associated with substantially increased odds of impairment in physical function.
Abstract: Introduction HIV-infected patients in the current treatment era can achieve normal life expectancies, but experience a high degree of medical and psychiatric comorbidity. Impaired physical function and pain, often in the context of mood disorders and substance abuse, are common in HIV-infected patients. The objective of this study was to investigate the relationship of pain, a modifiable condition, to functional impairment in HIV-infected patients, independent of mood disorders and substance abuse.

Journal ArticleDOI
TL;DR: A critical examination of the proposition that chronic pain is a disease cannot be supported on clinical and pathological grounds, as well as in terms of ways of knowing.
Abstract: Objective. The discovery of neuroplastic phenom- ena such as central sensitization of nociception has challenged pain theory to evolve, to encompass unpredictable and unlikely chronic pain states, and to cope with the emerging complexity of the brain. Recently, the proposition that chronic pain is a disease in its own right has gained currency, based upon functional and structural changes in the brain constituting a distinctive pathology. Proponents have expanded the theory to identify "eudynia" ("good" pain) and "maldynia" ("bad" pain). Methods. A critical examination of the proposition that chronic pain is a disease was conducted within the framework of evolution of pain medicine theory. Results. Three dominant theories were identified: specificity theory (the "hard-wired" nervous system); neuroplasticity theory (the "soft-wired" nervous system); and pain-as-a-disease. The pro- gression from specificity theory to neuroplasticity theory was based upon empirical evidence and con- ceptual clarity. The latter theory confronts the uncer- tainty and the unpredictability of pain, and offers explanations for conditions where ongoing noxious input is not discernible. However, not only does pain- as-a-disease elevate the neurophysiological mecha- nisms underlying the experience of chronic pain to the status of a disease, but also it conceives of pain as a "thing" that is itself capable of producing an effect. This reasoning is found to be faulty on two grounds: the confusion of pain as a symptom, a cause, and a pathology; and the fallacy that can arise when an interpretation is claimed to be a truth. Conclusions. The proposition that chronic pain is a disease cannot be supported on clinical and path- ological grounds, as well as in terms of ways of knowing. The promulgation of "good" and "bad" pain has the potential to obstruct necessary dialogue for advancing the science and treatment of pain. We suggest a way forward to resolve this impasse.

Journal ArticleDOI
TL;DR: Perceived negative stereotyping among chronic pain sufferers is common, particularly negative perceptions about physicians, and women with chronic vulvar pain who felt stigmatized were more likely to have sought care than those who did not feel stigmatized.
Abstract: Approximately 10% - 18% of American women have had symptoms consistent with vulvodynia at some point in their lives1-4. Among the estimated 116 million American chronic pain sufferers, women with vulvodynia play a significant role in the chronic pain epidemic due to their high rate of co-morbidity5-8, the subsequent psychosocial impact of this condition9-12, population-level economic costs13, the risk of reproductive consequences14,15, and the young age at which peak incidence of vulvodynia occurs16,17. The goal of medical intervention for vulvodynia is to reduce or eliminate pain, and in fact, remission from vulvar pain is thought to occur for some women18. However, unsuccessful treatment of vulvodynia, leading to prolonged pain, can profoundly affect a woman's sexual functioning19,20. Whereas successful intervention, which is often multidisciplinary, can lead to not only overall pain reduction but also nearly pain-free intercourse21, decreased depression and anxiety22, and improved psychological well-being23. Medical management of vulvodynia has only been moderately effective so it is unclear to what extent medical care influences resolution of symptoms for women with vulvodynia. 24-29. In addition, examining the role of medical therapy on remission among all women with vulvodynia may far overestimate its true effect because in reality only roughly half of women with vulvar pain seek medical care1,4. Reasons women choose not to seek medical care for their vulvar pain have not been elucidated. However, some studies have found that women with vulvodynia are apprehensive to speak about their pain with others9, and feelings of isolation and invalidation of their pain are common8. Although no previous studies regarding failure to seek medical care have been conducted among women with vulvodynia, studies of other chronic pain syndromes have identified that stigma, whether perceived, inadvertent, or real, contributes to estrangement from health care providers, particularly physicians30-32. Sampling from a large administrative healthcare system database that represents young women from the surrounding geographical area, we conducted a study that estimates the prevalence of perceived stereotyping, which may ultimately lead to stigma, regarding vulvar pain sufferers. We then determined whether perceived stigma was associated with the high level of failure to seek care among women with chronic vulvar pain.

Journal ArticleDOI
TL;DR: The local and referred pain elicited by active TrPs in the back and hip muscles contributes to pain symptoms in nonspecific LBP.
Abstract: Objective To investigate the difference in the presence of trigger points (TrPs) between patients with chronic nonspecific low back pain (LBP) and healthy people, and to determine the relationship of TrPs with the intensity of ongoing pain, disability, and sleep quality. Design A cross-sectional study. Setting The role of TrPs in LBP has not been determined. Patients Forty-two patients with nonspecific LBP (50% women), aged 23–55 years old, and 42 age- and sex-matched controls participated. Outcome Measures TrPs were bilaterally explored within the quadratus lumborum, iliocostalis lumborum, psoas, piriformis, gluteus minimus, and gluteus medius muscles in a blinded design. TrPs were considered active if the subject recognized the local and referred pain as familiar symptoms, and TrPs were considered latent if the pain was not recognized as a familiar symptom. Pain measures were collected with a numerical pain rate scale, disability was assessed with the Roland–Morris questionnaire, and sleep quality was determined with the Pittsburgh Sleep Quality Index. Results Patients with nonspecific LBP exhibited a greater disability and worse sleep quality than healthy controls ( P < 0.001). Patients with nonspecific LBP exhibited a mean of 3.5 ± 2.3 active TrPs. Further, patients with nonspecific LBP showed a greater ( P < 0.001) number of latent TrPs (mean: 2.0 ± 1.5) than healthy controls (mean: 1.0 ± 1.5). Active TrPs in the quadratus lumborum, iliocostalis lumborum, and gluteus medius muscles were the most prevalent in patients with nonspecific LBP. A greater number of active TrPs was associated with higher pain intensity (rs = 0.602; P < 0.001) and worse sleep quality (rs = 0.338; P = 0.03). Conclusions The local and referred pain elicited by active TrPs in the back and hip muscles contributes to pain symptoms in nonspecific LBP. Patients had higher disability and worse sleep quality than controls. The number of active TrPs was associated with pain intensity and sleep quality. It is possible that a complex interaction among these factors is present in patients with nonspecific LBP.

Journal ArticleDOI
TL;DR: Patients with LE may be subgrouped based on pain hypersensitivity and Doppler ultrasound into clinically meaningful subgroups with varying duration of symptoms and different degrees of central sensitization.
Abstract: OBJECTIVE.: To assess pain sensitivity and spreading hyperalgesia in lateral epicondylalgia (LE). SUBJECTS.: Twenty-two women with LE, and 38 controls were included. OUTCOME MEASURES.: Computerized cuff pressure algometry was used for assessment of pressure-pain threshold and tolerance. The stimulus was applied using a single (stimulation-area: 241 cm(2) ) or double-chambered (stimulation-area: 482 cm(2) ) tourniquet on the arm and leg. Spatial summation was expressed as the ratio between pressure-pain thresholds to single and double cuff-chamber stimulation. During 10-minute constant pressure stimulation at intensity relative to the individual pain threshold, the pain intensity was continuously recorded using an electronic visual analogue scale (VAS), and from this the degree of temporal summation was estimated. For LE, a Doppler ultrasound examination of the elbow was made to identify inflammation. RESULTS.: In LE compared with controls the pressure-pain threshold and tolerance were on average reduced by respectively 31% (nonsignificant) and 18% (nonsignificant) on the lower arm and by 32% (P < 0.05) and 22% (P < 0.05) on the lower leg (spreading sensitization). Within the LE group, pressure-pain thresholds were on average reduced by 20% (P < 0.05) and pain tolerance by 10% (nonsignificant) on the painful compared with the asymptomatic side. Spatial summation (P < 0.01) and temporal summation (P < 0.05) was facilitated in LE compared with controls. In LE patients without signs of peripheral inflammation assessed by Doppler ultrasound, temporal summation was significantly stronger than in patients with ongoing inflammation (P < 0.01). CONCLUSION.: Patients with LE may be subgrouped based on pain hypersensitivity and Doppler ultrasound into clinically meaningful subgroups with varying duration of symptoms and different degrees of central sensitization. These groups may require different pain management strategies.