The journal of pain : official journal of the American Pain Society
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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.
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Fibromyalgia (FM) is a chronic, widespread musculoskeletal pain disorder that is very prevalent in the general population (approximately 5%). Accumulating evidence suggests that FM is associated with central pain processing abnormalities, ie, central sensitization. Several previous studies of chronic pain patients, including FM, have shown gray matter atrophy of brain areas associated with sensory and affective pain processing. These findings, however, have not been confirmed in all FM studies. In this study, we investigated gray matter volumes of brain areas associated with pain-related areas of FM patients identified by functional brain imaging. Using voxel-based morphometric (VBM) analysis of magnetic resonance brain images, we compared 19 pain-related brain areas of 14 female FM patients and 11 healthy controls (NC). We found that FM patients had significantly less gray matter volumes than NC in 3 of these brain regions, including the anterior and mid-cingulate, as well as mid-insular cortices. Importantly, FM patients demonstrated neither global gray matter atrophy nor gray matter changes associated with depression, as shown in some studies. Using a more stringent analysis than other VBM studies, we provide evidence for decreased gray matter volumes in a number of pain-related brain areas in FM. Although the mechanisms for these gray matter changes are presently unclear, they may contribute to some of the core features of this chronic disorder including affective disturbances and chronic widespread pain. ⋯ Increasing evidence supports the association of chronic pain with accelerated gray matter atrophy in pain disorders like low back pain, IBS, and FM syndrome. However, cause-effect relationships between chronic pain and decreased gray matter volumes have not been established yet and will require future prospective studies.
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Persistent shoulder pain is a common complication after stroke. Its etiology and underlying mechanisms are not well understood and treatment is generally unsatisfactory. The objective of this study was to assess the role of central sensitization and disinhibition in chronic stroke patients with chronic PSSP (n = 19), pain-free stroke patients (n = 29), and healthy controls (n = 23). Positive and negative somatosensory symptoms and signs were assessed using clinical examination and electrical and mechanical quantitative sensory testing (QST). Conditioned pain modulation (CPM) was assessed by comparing QST thresholds before and after applying a cold pressor test. Sensory abnormalities were more frequently observed and more severe in patients with PSSP, including positive signs such as allodynia at the affected side and generalized hyperalgesia at the unaffected side. CPM was similar in stroke patients and healthy controls. This study showed that chronic PSSP was associated with several positive and negative somatosensory signs, implicating a role for central sensitization and possibly for disinhibition. Since the causal relationship remains unclear, and may be related to either neuroplasticity induced by ongoing nociception as well as to the neuropathic brain lesion, prospective studies are warranted. ⋯ The assessment of somatosensory symptoms and signs and endogenous pain modulation demonstrated a role for central sensitization and possibly for disinhibition in chronic PSSP. Prevention and treatment of PSSP could benefit from a more detailed analysis of both peripheral and central pain mechanisms.
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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.