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Biomedical subjects

Robert H Dworkin

Publications and source records attributed to Robert H Dworkin.

At least 19 recordsLinked to original sources
PubMed2006

Skin biopsy and quantitative sensory testing do not predict response to lidocaine patch in painful neuropathies.

Predictors of response to neuropathic pain treatment in patients with painful distal sensory neuropathies are lacking. The 5% lidocaine patch is believed to exert its effects on neuropathic pain via a local stabilizing effect on cutaneous sensory afferents. As such, it provides a model to assess whether the status of epidermal innervation as determined by skin biopsy or quantitative sensory testing (QST) of small- and large-diameter sensory afferents might serve as predictors of response to topical, locally active treatment. In this study we assessed associations between epidermal nerve fiber (ENF) densities, sensory nerve conduction studies (NCS), QST, and response to a 5% lidocaine patch in patients with painful distal sensory neuropathies. We observed no association between distal leg epidermal and subepidermal innervation and response to the lidocaine patch. Several patients with complete loss of distal leg ENF showed a response to the lidocaine patch. Similarly we observed no consistent association between treatment response and QST for vibration, cooling, warm, heat-pain, and cold-pain thresholds, or distal sensory NCS. Thus, distal-leg skin biopsy, QST, and sensory NCS cannot be used to identify patients with painful polyneuropathy likely to respond to a lidocaine patch in clinical practice. Further studies are required to clarify precisely the mechanism and site of action of the lidocaine patch in patients with peripheral neuropathic pain.

Aged↗
PubMed2006

Ion channel targets and treatment efficacy in neuropathic pain.

UNLABELLED: Chronic neuropathic pain due to injury or dysfunction of the nervous system remains a formidable treatment challenge in spite of a growing range of medication choices. We review current clinical research supporting the use of ion channel modulators for neuropathic pain states. New modes of local drug delivery, novel Ca2+ channel targets, and increased choices for drugs with activity at Na+channels are transforming this longstanding therapeutic strategy. Clinical decision making is increasingly informed by a more nuanced understanding of the role of voltage-gated Na+channels (VGSCs) and Ca2+ channels (VGCCs) in the pathophysiology of nerve injury. Although holding great promise for the future, mechanism-based approaches to treatment will require greater understanding of the analgesic mechanisms of drug action and of the relationships between pathophysiologic mechanisms and clinical presentation. PERSPECTIVE: Treatment options for neuropathic pain targeting ion channels have grown rapidly in the past decade. An evolving body of clinical research supports the widespread use of this longstanding therapeutic strategy. Improved efficacy of ion channel modulators hinges upon further elucidation of the relationship between signs and symptoms of pain and underlying pathophysiology.

Calcium Channel Blockers↗
PubMed2005

Placebo response in clinical trials of depression and its implications for research on chronic neuropathic pain.

This article reviews studies of the placebo response in antidepressant clinical trials, describes methods that have been attempted to decrease it, and discusses implications of the placebo response in depression for research on treatments for neuropathic pain. Literature reviews and research studies examining the placebo response in clinical trials of treatments for depression were reviewed. Existing data suggest that the placebo response in antidepressant clinical trials is substantial and that a high placebo response in a clinical trial is associated with a reduced likelihood of demonstrating the statistical superiority of antidepressant treatment vs. placebo. Attempts to decrease the placebo response in antidepressant clinical trials have generally not been effective. In addition, there is little evidence that decreasing the placebo response rate makes it more likely that superiority of active vs. placebo treatment will be demonstrated. Analyses of neuropathic pain clinical trial databases should be conducted to examine factors associated with trial outcomes. Aspects of neuropathic pain clinical trials that require further consideration or investigation include the following: (a) exclusion of patients with mild pain severity; (b) exclusion of patients with short episode duration; (c) maximizing reliability, validity, and responsiveness of outcome measures; (d) minimizing extraneous contact with investigative staff and other sources of nonspecific therapeutic effects; (e) trial duration; (f) minimizing the number of treatment groups; (g) flexible vs. fixed dose designs; (h) strategies for identifying patients and accelerating enrollment; (i) identification of run-in periods that reduce the placebo response rate; and (j) registration of clinical trials and publication of negative studies.

Antidepressive Agents↗
PubMed2005

Risk factors for acute pain and its persistence following breast cancer surgery.

Although more severe acute postoperative pain increases the risk of chronic pain following breast cancer surgery, few studies have examined the characteristics of patients who develop greater acute pain. To identify risk factors for acute pain and its persistence one month following breast cancer surgery, a sample of 114 women scheduled for breast cancer surgery was assessed preoperatively for demographic, clinical, and emotional functioning variables that were hypothesized to be associated with acute pain severity. Clinically meaningful postoperative pain was assessed at follow-up interviews 2, 10, and 30 days after surgery. In univariate analyses, the risk of clinically meaningful acute pain was increased among women who were younger, unmarried, had more invasive surgeries, and had greater preoperative emotional distress. In multiple logistic regression analyses, greater preoperative anxiety was the only variable that made an independent contribution to predicting clinically meaningful acute pain at 2 days after surgery whereas younger age, being unmarried, and preoperative anxiety each made an independent contribution to predicting clinically meaningful acute pain that persisted from 2 to 30 days after surgery. These results increase understanding of neurobiologic mechanisms and psychosocial processes that contribute to the development of acute pain following breast cancer surgery and have implications for the development of interventions to prevent it.

Acute Disease↗
PubMed2005

Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal pain and lowered pain threshold. Other prominent symptoms include disordered sleep and fatigue. FMS affects an estimated 2% of the population, predominantly women. This trial was designed to evaluate the efficacy and safety of pregabalin, a novel alpha(2)-delta ligand, for treatment of symptoms associated with FMS. METHODS: This multicenter, double-blind, 8-week, randomized clinical trial compared the effects of placebo with those of 150, 300, and 450 mg/day pregabalin on pain, sleep, fatigue, and health-related quality of life in 529 patients with FMS. The primary outcome variable was the comparison of end point mean pain scores, derived from daily diary ratings of pain intensity, between each of the pregabalin treatment groups and the placebo group. RESULTS: Pregabalin at 450 mg/day significantly reduced the average severity of pain in the primary analysis compared with placebo (-0.93 on a 0-10 scale) (P </= 0.001), and significantly more patients in this group had >/=50% improvement in pain at the end point (29%, versus 13% in the placebo group; P = 0.003). Pregabalin at 300 and 450 mg/day was associated with significant improvements in sleep quality, fatigue, and global measures of change. Pregabalin at 450 mg/day improved several domains of health-related quality of life. Dizziness and somnolence were the most frequent adverse events. Rates of discontinuation due to adverse events were similar across all 4 treatment groups. CONCLUSION: Pregabalin at 450 mg/day was efficacious for the treatment of FMS, reducing symptoms of pain, disturbed sleep, and fatigue compared with placebo. Pregabalin was well tolerated and improved global measures and health-related quality of life.

Adult↗
PubMed2005

Assessment of pain quality in chronic neuropathic and nociceptive pain clinical trials with the Neuropathic Pain Scale.

UNLABELLED: Although a number of measures of pain qualities exist, little research has examined the potential for these measures to identify the unique effects of pain treatments on different pain qualities. We examined the utility of the Neuropathic Pain Scale (NPS) for assessing changes in pain qualities after open label lidocaine patch 5% in 3 samples of patients: patients with peripheral neuropathic pain, low back pain, and osteoarthritis. With one exception ("cold" pain in subjects with low back pain), each of the NPS items showed significant change after open label lidocaine patch. In addition, significantly larger changes were observed for the NPS items reflecting global pain intensity and pain unpleasantness and for items assessing sharp and deep pain than for items assessing cold, sensitive, and itchy pain. The pattern of changes in pain qualities did not differ across the 3 diagnostic groups, but it did differ from the patterns of changes in pain qualities associated with other analgesic treatments. The results support the potential utility of the NPS for assessing the patterns of changes in pain qualities that can be observed after pain treatment. PERSPECTIVE: Pain clinical trials that include measures of pain qualities, such as the NPS, might identify distinct patterns of treatment effects on those pain qualities. This research might be used to help clinicians target analgesics to match the specific qualities associated with a patient's pain and to better understand the mechanisms of analgesic effects in drug development programs.

Administration, Cutaneous↗
PubMed2005

A randomized, placebo-controlled trial of bupropion sustained release in chronic low back pain.

UNLABELLED: Clinical trials of the efficacy of antidepressant drugs in patients with chronic low back pain have had mixed results, possibly because of the different mechanisms of action of the drugs that have been studied. Because bupropion has a mechanism of action that differs from other antidepressants and has shown efficacy in neuropathic pain, a randomized, placebo-controlled, 2-period crossover trial was conducted to evaluate its efficacy in subjects with chronic low back pain. The primary efficacy variable was mean daily diary pain intensity ratings, and secondary pain intensity and relief outcomes included weekly pain intensity ratings, the McGill Pain Questionnaire (MPQ) Present Pain Intensity scale, pain relief ratings, and satisfaction with pain relief ratings. Adverse events were also assessed throughout the trial. Analyses were performed of an intention-to-treat sample of 44 patients, only 3 of whom met criteria for neuropathic low back pain. Daily and weekly pain intensity ratings, the MPQ Present Pain Intensity scale, and pain relief ratings were not significantly different following treatment with bupropion sustained release (SR) vs. placebo. These results suggest that bupropion SR was not significantly better than placebo in the treatment of patients with non-neuropathic chronic low back pain. PERSPECTIVE: Antidepressant medications that have both noradrenergic and serotonergic effects appear to have greater efficacy in patients with chronic low back pain than those with only serotonergic activity. We studied bupropion because it inhibits the reuptake of both norepinephrine and dopamine, but found no evidence of efficacy in patients with non-neuropathic chronic low back pain.

Adult↗
PubMed2005

Psychosocial risk factors for postherpetic neuralgia: a prospective study of patients with herpes zoster.

UNLABELLED: The results of previous studies using retrospective methods or small samples have suggested that there may be psychosocial risk factors for postherpetic neuralgia (PHN). We conducted a prospective study in which 110 patients with herpes zoster were assessed within the first month after rash onset with measures of acute pain and five broad domains of psychosocial functioning-physical, role, social, and emotional functioning, and stress and social support. Twenty of the 102 patients with follow-up data were diagnosed with PHN, defined as pain that had persisted for 4 months after rash onset. Measures of role functioning, personality disorder symptoms, and disease conviction during herpes zoster each made independent contributions to predicting either presence or intensity of PHN in logistic and linear regression analyses that controlled for relevant demographic and clinical variables, including age and acute pain intensity. These findings indicate that psychosocial variables are risk factors for the development of PHN. PERSPECTIVE: The results of this prospective study of patients with herpes zoster suggest that future research on the mechanisms and prevention of PHN should consider psychosocial as well as neurobiologic processes.

Activities of Daily Living↗
PubMed2005

Effects of intradermal foot and forearm capsaicin injections in normal and vulvodynia-afflicted women.

Cutaneous response to capsaicin has been used to assess central sensitization in pain research. This study compared the response to intradermal capsaicin in the forearm and foot of vulvar vestibulitis (vestibulodynia)-afflicted cases and controls. We hypothesized that cases will experience greater spontaneous pain, larger cutaneous areas of punctate hyperalgesia and dynamic allodynia, and greater vascular flow than controls. We also hypothesized enhanced post-injection pain in the foot compared to the forearm based on dermatome proximity of the foot and vulva. Methods. Ten vulvar vestibulitis syndrome (VVS) cases and 10 age and ethnically matched controls underwent two randomized, cross-over trials with intra-dermal injections of capsaicin or a saline placebo in the forearm and foot. Outcome measures included spontaneous pain level, surface area of punctate hyperalgesia, surface area of dynamic allodynia, cutaneous blood flow, regional skin temperature and vital signs. Results. VVS cases experienced greater spontaneous pain, punctate hyperalgesia and dynamic allodynia than pain-free controls. Within the VVS group, post-capsaicin spontaneous pain, punctate hyperalgesia and dynamic allodynia were similar in the forearm and foot. Post-capsaicin blood flow did not differ between cases and controls by anatomic site. Measures of depression and anxiety correlated with spontaneous pain intensity but did not correlate with measures of hyperalgesia, allodynia, or blood flow. VVS cases had higher resting pulse rates and lower resting systolic blood pressures than in controls. Conclusion. VVS patients show enhancement of post-capsaicin pain response extending far beyond the anatomic location of the primary complaint.

Adult↗
PubMed2005

Pregabalin.

Explore the source record for details and available documents.

Analgesics↗
PubMed2005

Contributions of physical and sexual abuse to women's experiences with chronic pelvic pain.

OBJECTIVE: To examine the roles of physical and sexual abuse in women with chronic pelvic pain using multi-dimensional pain assessment and to compare the chronic pelvic pain experiences of women with physical abuse to those of women with sexual abuse. STUDY DESIGN: Structured questionnaires were used to measure self-reported abuse, pain severity, psychological distress, physical functioning, interpersonalfunctioning, and coping in 63 women attending a tertiary care gynecologic clinic for diagnosis and treatment of chronic pelvic pain. RESULTS: Women with chronic pelvic pain who reported abuse demonstrated significantly more psychological distress than did women who reported no abuse, but there were no differences in pain severity, physical functioning, interpersonal functioning or coping. Women with physical abuse reported more overall psychological distress, depression, anxiety and somatization than women who reported no physical abuse. Women who reported sexual abuse showed more overall psychological distress and anxiety than women who reported no sexual abuse. While physical abuse was more consistently associated with psychological distress than was sexual abuse, both types of abuse were risk factors for distress. CONCLUSION: These results suggest that both physical and sexual abuse are associated with psychological distress in women with chronic pelvic pain but not with other domains of pain experience. Additional research to improve identification and treatment of women with both chronic pelvic pain and abuse is indicated.

Adult↗
PubMed2004

Acute pain in herpes zoster and its impact on health-related quality of life.

Although the effects of postherpetic neuralgia on physical and emotional functioning have been examined in a number of studies, the impact of acute pain in herpes zoster ("shingles") on health-related quality of life has been neglected. We describe the characteristics of herpes zoster pain and examine its relationship to physical, role, social, and emotional functioning in 110 patients with herpes zoster. When we controlled for relevant covariates, we found that greater pain burden, as assessed by the product of pain intensity and duration, was associated with poorer physical functioning, increased emotional distress, and decreased role and social functioning. The results demonstrate that herpes zoster pain has broad effects on the daily lives of patients and on their emotional health. The increasing incidence of herpes zoster that can be anticipated as the population ages requires that clinical trials that examine interventions to prevent or treat herpes zoster pain be given a high priority.

Acute Disease↗
PubMed2004

What should be the core outcomes in chronic pain clinical trials?

A consensus conference with representatives from academia, governmental agencies, and the pharmaceutical industry met and concluded that clinical trials designed to assess the efficacy and effectiveness of treatments for chronic pain should consider outcomes in six core domains: pain, physical functioning, emotional functioning, patient global ratings of satisfaction, negative health states and adverse events, and patient disposition. In addition, it was acknowledged that there are many secondary domains that might be of importance and should be included in trials depending on the nature of the treatment and population to whom the treatment is targeted.

Chronic Disease↗
PubMed2004

Risk factors for postherpetic neuralgia in patients with herpes zoster.

OBJECTIVES: To identify risk factors for postherpetic neuralgia (PHN) using a validated definition of this chronic neuropathic pain syndrome, to determine combinations of risk factors that identify patients with a high risk of developing PHN, and to examine the characteristics of patients with subacute herpetic neuralgia, that is, pain that persists beyond the acute phase of herpes zoster but that resolves before PHN can be diagnosed. METHODS: The authors examined baseline and follow-up data from 965 herpes zoster patients enrolled within 72 hours of rash onset in two clinical trials of famciclovir. RESULTS: Univariate and multivariate analyses indicated that older age, female sex, presence of a prodrome, greater rash severity, and greater acute pain severity made independent contributions to identifying which patients developed PHN. Patients with subacute herpetic neuralgia who did not develop PHN were significantly younger and had less severe acute pain than PHN patients but were significantly more likely to have severe and widespread rash than patients without persisting pain. CONCLUSIONS: The independent contributions to the prediction of PHN made by older age, female sex, presence of a prodrome, greater rash severity, and greater acute pain severity suggest that these risk factors reflect different mechanisms that each contribute to the development of PHN. Subacute herpetic neuralgia that does not progress to PHN may reflect peripheral tissue damage and inflammation caused by a particularly severe or widespread rash.

2-Aminopurine↗