Articles: hyperalgesia.
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Neuroscience letters · Feb 2013
Treadmill running and static stretching improve long-lasting hyperalgesia, joint limitation, and muscle atrophy induced by cast immobilization in rats.
The effects of exercise on chronic pain induced by immobilization are incompletely understood. The purpose of this study was to investigate whether 30min of treadmill running (TR; active exercise) and 10min of static stretching (SS; passive exercise) of the immobilized hindlimb reduce widespread chronic pain, joint limitation, and hindlimb muscle atrophy induced by cast immobilization in rats. One hindlimb of Sprague Dawley (SD) rats was immobilized for 2 weeks with a cast, and remobilization was conducted for 7 weeks. ⋯ Both forms of exercise significantly inhibited mechanical hyperalgesia in the calf and hindpaw in immobilized rats. Range-of-motion limitations in the knee and ankle joints and calf muscle atrophy after cast removal were also decreased by both TR and SS. This study is the first to demonstrate the beneficial effect of TR and SS on widespread chronic pain, joint limitation, and muscle atrophy in a cast-immobilized rat model.
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Intraoperative nerve lesions can lead to chronic postoperative pain. There are conflicting data as to whether or not anaesthetics administered intraoperatively are beneficial. We investigated if remifentanil administered at the time of nerve injury was able to attenuate neuropathic hypersensitivity. ⋯ High-dose remifentanil administered at the time of transection of the spinal nerve at L5 prevents subsequent thermal hyperalgesia.
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T-type calcium channels encoded by the Ca(V)3.2 isoform are expressed in nociceptive primary afferent neurons where they contribute to hyperalgesia and thus are considered as a potential therapeutic target to treat pathological pain. Here we report that the small organic state-dependent T-type channel antagonist TTA-A2 efficiently inhibits recombinant and native Ca(V)3.2 currents. Although TTA-A2 is a pan Ca(V)3 blocker, it demonstrates a higher potency for Ca(V)3.2 compared to Ca(V)3.1. ⋯ Oral administration of TTA-A2 produced a dose-dependent reduction of hypersensitivity in an IBS model, demonstrating its therapeutic potential for the treatment of pathological pain. Overall, our results suggest that the high potency of TTA-A2 in the depolarized state strengthen its analgesic efficacy and selectivity toward pathological pain syndromes. This characteristic would be beneficial for the development of analgesics targeting T-type channels, in particular for the treatment of pain associated with IBS.
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Inflammatory pain severely affects the quality of life of millions of individuals worldwide. Prostaglandin E2 (PGE2), a pain mediator enriched in inflamed tissues, plays a pivotal role in nociceptor sensitization and in the genesis of inflammatory pain. Its EP4 receptor mainly mediates its role in inflammatory pain. ⋯ Intraplantar injection of complete Freud's adjuvant increases both total and cell-surface EP4 levels of L4-6 DRG neurons, an event suppressed by a cyclooxygenase-2 inhibitor or a selective EP4 antagonist, suggesting that PGE2/EP4 signalling in inflamed paw contributes to EP4 synthesis and export in DRG neurons, thus sensitizing nociceptors during inflammation. We conclude that PGE2/EP4 signalling-induced EP4 externalization in DRG neuron is a novel mechanism underlying nociceptor sensitization and inflammatory pain. Blocking EP4 externalization could open a novel therapeutic avenue to treat inflammatory pain.
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It is known that interleukin-17 (IL-17) is associated with autoimmune disorders and that peripheral IL-17 plays a role in arthritis and neuropathic pain. The present study investigated the possibility of spinal cell expression of IL-17 during inflammatory pain and possible IL-17 involvement in such pain. Hyperalgesia was induced by injecting complete Freund adjuvant (CFA, 0.08mL, 40μg Mycobacterium tuberculosis) into one hind paw of the rat. ⋯ Spinal cords were removed for IL-17 immunostaining, double immunostaining of IL-17/cell markers and IL-17 receptor A (IL-17RA)/NR1, for Western blot testing of IL-17, p-NR1, IL-17RA, and GFAP, for in situ IL-17RA hybridization, and for real time polymerase chain reaction of IL-17RA. The data reveal that IL-17 is up-regulated in activated and nonactivated astrocytes; that IL-17RA is localized in NR1-immunoreactive neurons and up-regulated; and that IL-17 antibody at 2μg/rat significantly increased PWL (P<.05) and decreased p-NR1 and IL-17RA compared to control in CFA- and IL-17-injected rats. The results suggest that spinal IL-17 is produced by astrocytes and enhances p-NR1 to facilitate pain.