Pain
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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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Randomized Controlled Trial
GDNF levels in the lower lip skin in a rat model of trigeminal neuropathic pain: implications for nonpeptidergic fiber reinnervation and parasympathetic sprouting.
Trigeminal neuropathic pain is associated with trigeminal nerve damage. Significant remodeling of the peripheral nervous system may contribute to the pain; however, the changes and the factors that drive them have not been well described. In this study, a partial injury of the mental nerve of the rat, a purely sensory branch of the trigeminal nerve, resulted in prolonged mechanical allodynia in the lower lip skin persisting up to 4 months. ⋯ Meanwhile, the glial cell line-derived growth factor (GDNF) showed a quick upregulation in the skin after nerve lesioning, with levels peaking at 4 weeks. This suggests that an excess of GDNF in the skin drives the nonpeptidergic C-fiber regeneration and parasympathetic fiber sprouting in the upper dermis, and could be an important mechanism in trigeminal neuropathic pain. This article provides an in-depth description of the changes in nonpeptidergic fibers in the skin after nerve lesioning, and measures, for the first time, GDNF protein levels in the skin after a nerve lesion, providing strong evidence for the role of GDNF in modulating innervation of the nonpeptidergic and parasympathetic fibers in the skin after injury.
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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.