To evaluate the efficacy and safety of pregabalin in the treatment of postherpetic neuralgia (PHN).
The authors conducted a multicenter, parallel-group, double-blind, placebo-controlled, 8-week, ...randomized clinical trial in PHN, defined as pain for 3 or more months following herpes zoster rash healing. Patients (n = 173) were randomized to treatment with pregabalin or placebo. Patients randomized to pregabalin received either 600 mg/day (creatinine clearance > 60 mL/min) or 300 mg/day (creatinine clearance 30 to 60 mL/min). The primary efficacy measure was the mean of the last seven daily pain ratings. Secondary endpoints included additional pain ratings, sleep interference, quality of life, mood, and patient and clinician ratings of global improvement.
Pregabalin-treated patients had greater decreases in pain than patients treated with placebo (endpoint mean scores 3.60 vs 5.29, p = 0.0001). Pain was significantly reduced in the pregabalin-treated patients after the first full day of treatment and throughout the study, and significant improvement on the McGill Pain Questionnaire total, sensory, and affective pain scores was also found. The proportions of patients with >or=30% and >or=50% decreases in mean pain scores were greater in the pregabalin than in the placebo group (63% vs 25% and 50% vs 20%, p = 0.001). Sleep also improved in patients treated with pregabalin compared to placebo (p = 0.0001). Both patients and clinicians were more likely to report global improvement with pregabalin than placebo (p = 0.001). Given the maximal dosage studied, pregabalin had acceptable tolerability compared to placebo despite a greater incidence of side effects, which were generally mild to moderate in intensity.
Treatment of PHN with pregabalin is safe, efficacious in relieving pain and sleep interference, and associated with greater global improvement than treatment with placebo.
A number of high-quality studies have recently been published that examine the association between neuropathic pain and health-related quality of life (HRQoL). The current review identified 52 such ...studies in patients with six neuropathic pain conditions associated with lesions of either the peripheral (postsurgical neuropathic pain associated with breast and amputation surgery, postherpetic neuralgia, and painful diabetic neuropathy) or central (poststroke pain, spinal cord injury pain, multiple sclerosis pain) nervous system. The results provide strong evidence that the presence and severity of neuropathic pain are associated with greater impairments in a number of important HRQoL domains. However, the evidence also indicates that this impact varies somewhat as a function of the HRQoL domain being considered and that different measures of HRQoL are differentially sensitive to the effects of neuropathic pain. The findings have important implications for the selection of HRQoL domains and measures to use in clinical trials and in clinical research on HRQoL in persons with neuropathic pain and suggest that a biopsychosocial (as opposed to a primarily biomedical) approach would be appropriate for understanding and treating neuropathic pain.
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.
Abstract A number of different treatments for neuropathic pain have been studied, but the literature is sizable, rapidly evolving, and lacks important information about practical aspects of patient ...management. Under the auspices of the International Association for the Study of Pain (IASP) Neuropathic Pain Special Interest Group (NeuPSIG), a consensus process was used to develop evidence-based guidelines for the pharmacologic management of neuropathic pain that take into account clinical efficacy, adverse effects, impact on health-related quality of life, convenience, and costs. On the basis of randomized clinical trials, medications recommended as first-line treatments for neuropathic pain included certain antidepressants (i.e., tricyclic antidepressants and dual reuptake inhibitors of both serotonin and norepinephrine), calcium channel α2 -δ ligands (i.e., gabapentin and pregabalin), and topical lidocaine. Opioid analgesics and tramadol were recommended as second-line treatments that can be considered for first-line use in selected clinical circumstances. Other medications that generally would be used as third-line treatments include certain other antidepressant and antiepileptic medications, topical capsaicin, mexiletine, and N -methyl- d -aspartate receptor antagonists. Two other national and international associations recently published pharmacologic treatment guidelines for neuropathic pain, which are summarized and contrasted with the NeuPSIG recommendations. Recent guidelines for the use of neurostimulation for the treatment of neuropathic pain also are summarized. For all treatments for neuropathic pain, long-term studies, head-to-head comparisons, and studies of treatment combinations are a priority for future research.
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.
We evaluated the impact on survival of antithymocyte globulin conditioning (TLI-ATG) with radiation (RT) boost to high risk or residual disease before allogeneic hematopoietic cell transplant ...(allo-HCT) for adults with lymphoma (excluding mycosis fungoides and low-grade NHL other than SLL/CLL). Of 251 evaluable patients, 36 received an RT boost within 3 months of allo-HCT at our institution from 2001 to 2016. At the time of TLI-ATG, patients who received boost vs no boost had a lower rate of CR (11% vs 47%, p = 0.0003), higher rates of bulky disease (22% vs 4%, p < 0.0001), extranodal disease (39% vs 5%, p < 0.0001), and positive PET (75% vs 28%, p < 0.00001). In the boost group, the median (range) largest axial lesion diameter was 5.2 cm (1.8-22.3). Median follow-up was 50.2 months (range: 1-196). There was no significant difference in OS, time to recurrence, or time to graft failure with vs without boost. A trend toward higher percent donor CD3
chimerism was seen with vs without boost (p = 0.0819). The worst boost-related toxicity was grade 2 dermatitis. RT boost may help successfully mitigate the risk of high risk or clinically evident residual disease in adults with lymphoma undergoing allo-HCT.
Neuropathic pain is caused by a lesion or disease of the somatosensory system, including peripheral fibres (Aβ, Aδ and C fibres) and central neurons, and affects 7-10% of the general population. ...Multiple causes of neuropathic pain have been described and its incidence is likely to increase owing to the ageing global population, increased incidence of diabetes mellitus and improved survival from cancer after chemotherapy. Indeed, imbalances between excitatory and inhibitory somatosensory signalling, alterations in ion channels and variability in the way that pain messages are modulated in the central nervous system all have been implicated in neuropathic pain. The burden of chronic neuropathic pain seems to be related to the complexity of neuropathic symptoms, poor outcomes and difficult treatment decisions. Importantly, quality of life is impaired in patients with neuropathic pain owing to increased drug prescriptions and visits to health care providers, as well as the morbidity from the pain itself and the inciting disease. Despite challenges, progress in the understanding of the pathophysiology of neuropathic pain is spurring the development of new diagnostic procedures and personalized interventions, which emphasize the need for a multidisciplinary approach to the management of neuropathic pain.
Neuropathic pain (NP) is often refractory to pharmacologic and noninterventional treatment. On behalf of the International Association for the Study of Pain Neuropathic Pain Special Interest Group, ...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 poststroke 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 radiofrequency lesions for radiculopathy. No other conclusive recommendations can be made due to the poor quality of available 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 noninterventional treatments.
OBJECTIVEAn overview is presented of neuropathic pain syndromes, their characteristic symptoms and signs, and recent approaches to identifying their pathophysiologic mechanisms.
DESIGNThe results of ...recent clinical studies of neuropathic pain are reviewed. Chronic neuropathic pain syndromes are emphasized because these long-lasting and often disabling conditions present a much greater challenge for the clinician than acute pain. Peripheral neuropathic syndromes have received greater attention in the research literature than central pain, and studies of syndromes such as postherpetic neuralgia and painful diabetic neuropathy provide the basis for current knowledge of neuropathic pain.
CONCLUSIONSPrecise estimates of the prevalence of neuropathic pain are not available, but chronic neuropathic pain may be much more common than has generally been appreciated and its prevalence can be expected to increase in the future. There is considerable agreement that both peripheral and central processes contribute to many chronic neuropathic pain syndromes, and that these different mechanisms may explain the qualitatively different symptoms and signs that patients experience. The limitations of existing treatments for neuropathic pain and the inability to provide relief for many patients has stimulated ongoing studies that examine different approaches to preventing neuropathic pain.
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