The journal of pain : official journal of the American Pain Society
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Review Comparative Study
Systematic review of the comparative effectiveness of antiepileptic drugs for fibromyalgia.
Fibromyalgia is a difficult-to-treat chronic pain syndrome that affects 2% of the US population. Pregabalin is an antiepileptic recently FDA approved for fibromyalgia treatment. Other antiepileptics have been suggested for treatment. This systematic review examines the relative benefits and harms of antiepileptic drugs in the treatment of fibromyalgia. A literature search was conducted and 8 studies matched criteria (7 studies of pregabalin, 1 of gabapentin). Both drugs reduced mean pain scores more than placebo at a modest rate (pregabalin, 38% to 50%; gabapentin, 51%). In a 6-month trial of pregabalin responders, 32% continued to have response at 6 months, with a mean time to loss of response of 34 days. Compared to placebo, the drugs had similarly high rates of adverse events and withdrawals. Without a head-to-head trial it is not possible to conclude if 1 antiepileptic is more effective or harmful than the other, although limited evidence suggests potential differences. Future studies must directly compare the drugs, include a more broadly defined population, examine long term benefits and harms, and include cointerventions. We conclude that pregabalin and gabapentin are modestly effective for the treatment of fibromyalgia but that their long-term safety and efficacy remain unknown. ⋯ This systematic review evaluates the benefits and harms of using the antiepileptic drugs gabapentin and pregabalin for the treatment of fibromyalgia. Conclusions from this paper can help clinicians to more effectively treat the pain associated with fibromyalgia.
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Global ratings of treatment satisfaction and improvement can provide an opportunity for patients to aggregate multiple aspects of their treatment into a single measure of its perceived benefits and disadvantages. Although such measures have been recommended for chronic pain clinical trials, only limited data are available that address the hypothesis that they reflect multiple aspects of patients' treatment experience. Our objective was to identify the factors that make independent contributions to ratings of treatment satisfaction. We analyzed data from 5 open-label clinical trials of lidocaine patch 5% in osteoarthritis knee pain and chronic low back pain that were 2 to 12 weeks in duration. A total of 383 patients completed the Patient Global Assessment of Treatment Satisfaction scale and measures of pain, interference with physical and emotional functioning, sleep interference, and adverse events. The results of multivariate analyses indicated that improvements in measures of pain intensity, pain relief, and interference with physical functioning each made independent contributions to treatment satisfaction in both groups of patients. Improvements in interference with emotional functioning and sleep and the presence and severity of adverse events were not associated with satisfaction. ⋯ Measures of treatment satisfaction can reflect different aspects of the patient's treatment response, including improvements in pain and physical functioning. Increased understanding of such global measures may facilitate development of clinical trial outcomes that allow patients to evaluate with minimal burden those aspects of the treatment experience they consider personally meaningful.
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A large proportion of oncology outpatients with bone metastasis report unrelieved pain that significantly interferes with daily functioning and quality of life. However, little is known about the longitudinal pattern of pain intensity and analgesic prescriptions or use. Moreover, despite considerable advantages, the use of sophisticated statistical techniques, such as hierarchical linear modeling (HLM) has not been applied to the study of pain and analgesic outcomes. In a prospective longitudinal study, HLM was used to explore predictors of pain intensity and analgesic prescription and intake at the time of enrollment into the study (intercept) and over the course of 6 weeks (trajectory) in a sample of oncology outpatients with bone metastasis who received standard care for pain. In addition to corroborating known predictors of pain intensity, previously unrecognized variables were found that appear to affect both pain and analgesic outcomes. Importantly, some of the predictors of the trajectories of pain intensity and analgesic use (ie, pain-related distress and Pain Management Index (PMI) scores) are particularly amenable to interventions. Findings from this study suggest that sophisticated statistical modeling can be used in pain research to identify individual risk factors and propose novel targets that can be used to improve pain management in oncology outpatients with bone metastasis. ⋯ Findings from this study suggest that a large amount of inter-individual variability exists in patients' experiences with cancer pain and analgesic use. Future studies need to elucidate the mechanisms that underlie these differences.
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Females are disproportionately affected by irritable bowel syndrome (IBS) with menstrual cycle-dependent fluctuations in abdominal pain suggesting a role for ovarian hormones. IBS patients also exhibit greater activation of brain areas involved in pain affect such as the amygdala, yet the role of supraspinal processes in the effects of ovarian hormones on visceral pain is largely unexplored. The goal of the current study was to determine whether sex steroids act at the level of the amygdala to alter colonic pain sensitivity. Ovariectomized rats received implants on the amygdala of progesterone, estradiol, progesterone combined with estradiol, or cholesterol as a control to examine the involvement of the amygdala in ovarian hormone-mediated changes in visceral sensitivity. Visceral sensitivity was quantified as the number of abdominal contractions, a visceromotor response (VMR), in response to graded pressures of colorectal distension (CRD). Somatic sensitivity was also assessed by measuring the mechanical force required to elicit hindpaw withdrawal. Elevated levels of progesterone and/or estradiol on the amygdala heightened the responsiveness to CRD; in contrast, neither estradiol nor progesterone altered somatic sensation. Furthermore, administration of progesterone or estradiol to areas adjacent to the amygdala did not affect visceral sensitivity. Future studies will address the specific steroid receptors mediating the effects of progesterone and estradiol. ⋯ To our knowledge, this study represents the first description of a specific brain site mediating the effects of ovarian steroids on visceral sensitivity. These data also suggest that an amygdala-dependent mechanism may be responsible, at least in part, for the exacerbation of visceral symptomatology in females.
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To investigate the pain-modulatory effects of a local inflammatory stimulus on pain elsewhere in the body, capsaicin was applied topically to the forearm of 14 healthy female volunteers. Pressure-pain thresholds and sensitivity to sharpness were assessed on each side of the forehead twice per day during 48 hours of capsaicin treatment, and in the treated and contralateral forearm before and at the end of treatment. Heat was applied to the treated area to rekindle pain at times of forehead assessment. Hyperalgesia to sharpness, but not pressure pain, developed in the treated area whereas sensations remained stable in the contralateral forearm. Sharpness ratings decreased bilaterally in the forehead after 6 hours of treatment, and ipsilateral analgesia to pressure pain developed in the forehead when the capsaicin site was heated after 48 hours of treatment. These findings suggest that pain modulation involves unilateral regulatory mechanisms in addition to local and generalized pain control. The dissociated changes to sharpness and pressure pain indicate distinct cutaneous and deep central pain pathways. ⋯ The findings lend support to an increasing body of research which demonstrates that pain modulation involves hemilateral mechanisms in addition to local and generalized controls. Elucidation of mechanisms that modulate ipsilateral pain processing may help to clarify the pathophysiology of complex regional pain syndrome, which is characterized by hemilateral hyperalgesia.