Pain
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Neuropathic pain is often "spontaneous" or "stimulus-independent." Such pain may result from spontaneous discharge in primary afferent nociceptors in injured peripheral nerves. However, whether axotomized primary afferent nociceptors give rise to pain is unclear. The rostral anterior cingulate cortex (rACC) mediates the negative affective component of inflammatory pain. ⋯ Lesion of the rACC did not block cocaine-induced reward, indicating that rACC blockade did not impair memory encoding or retrieval but did impair spontaneous aversiveness. These data indicate that spontaneous pain arising from injured nerve fibers produces a tonic aversive state that is mediated by the rACC. Identification of the circuits mediating aversiveness of chronic pain should facilitate the development of improved therapies.
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The neuropeptide bradykinin (BK) sensitizes nociceptor activation following its release in response to inflammatory injury. Thereafter, the bioactivity of bradykinin is controlled by the enzymatic activities of circulating peptidases. One such enzyme, the metalloendopeptidase EC3.4.24.15 (EP24.15), is co-expressed with bradykinin receptors in primary afferent neurons. ⋯ In addition, bradykinin-induced sensitization of TRPV1 activation was increased in the presence of the EP24.15/16 inhibitor JA-2. Furthermore, behavioral analyses illustrated a significant dose-response relationship between JA-2 and bradykinin-mediated thermal hyperalgesia. These results indicate an important physiological role for the metallopeptidases EP24.15 and EP24.16 in regulating bradykinin-mediated sensitization of primary afferent nociceptors.
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Multicenter Study
Elevated levels of gonadotrophins but not sex steroids are associated with musculoskeletal pain in middle-aged and older European men.
The aim of this study was to determine the association of hormone levels with the occurrence of musculoskeletal pain. Men ages 40 to 79 years were recruited from population registers in 8 European centres. Subjects were asked to complete a postal questionnaire, which enquired about lifestyle and the occurrence of musculoskeletal pain over the past month. ⋯ Compared with those in the lowest tertile of LH, those in the highest tertile were more likely to report some pain (vs no pain, RRR=1.28; 95% CI 1.09 to 1.50) and also CWP (vs no pain, RRR=1.51; 95% CI 1.10 to 2.07). Similar results were found for FSH. Gonadotrophins, but not sex steroid hormone levels, are associated with musculoskeletal pain in men.
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Randomized Controlled Trial
Long-term maintenance of the analgesic effects of transcranial magnetic stimulation in fibromyalgia.
We assessed for the first time the long-term maintenance of repetitive transcranial magnetic stimulation (rTMS)-induced analgesia in patients with chronic widespread pain due to fibromyalgia. Forty consecutive patients were randomly assigned, in a double-blind fashion, to 2 groups: one receiving active rTMS (n=20) and the other, sham stimulation (n=20), applied to the left primary motor cortex. The stimulation protocol consisted of 14 sessions: an "induction phase" of 5 daily sessions followed by a "maintenance phase" of 3 sessions a week apart, 3 sessions a fortnight apart, and 3 sessions a month apart. ⋯ Active rTMS significantly reduced pain intensity from day 5 to week 25. These analgesic effects were associated with a long-term improvement in items related to quality of life (including fatigue, morning tiredness, general activity, walking, and sleep) and were directly correlated with changes in intracortical inhibition. In conclusion, these results suggest that TMS may be a valuable and safe new therapeutic option in patients with fibromyalgia.
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Randomized Controlled Trial
Cancer Health Empowerment for Living without Pain (Ca-HELP): effects of a tailored education and coaching intervention on pain and impairment.
We aimed to determine the effectiveness of a lay-administered tailored education and coaching (TEC) intervention (aimed at reducing pain misconceptions and enhancing self-efficacy for communicating with physicians) on cancer pain severity, pain-related impairment, and quality of life. Cancer patients with baseline "worst pain" of ≥4 on a 0-10 scale or at least moderate functional impairment due to pain were randomly assigned to TEC or enhanced usual care (EUC) during a telephone interview conducted in advance of a planned oncology office visit (265 patients randomized to TEC or EUC; 258 completed at least one follow-up). Patients completed questionnaires before and after the visit and were interviewed by telephone at 2, 6, and 12 weeks. ⋯ The improvement in pain-related impairment was not sustained at 6 and 12 weeks. There were no significant intervention by subgroup interactions (P>.10). We conclude that TEC, compared with EUC, resulted in improved pain communication self-efficacy and temporary improvement in pain-related impairment, but no improvement in pain severity.