Articles: hyperalgesia.
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Endothelin-1 (ET-1) is unique among a broad range of hyperalgesic agents in that it induces hyperalgesia in rats that is markedly enhanced by repeated mechanical stimulation at the site of administration. Antagonists to the ET-1 receptors, ET(A) and ET(B), attenuated both initial as well as stimulation-induced enhancement of hyperalgesia (SIEH) by endothelin. However, administering antisense oligodeoxynucleotide to attenuate ET(A) receptor expression on nociceptors attenuated ET-1 hyperalgesia but had no effect on SIEH, suggesting that this is mediated via a non-neuronal cell. ⋯ Compatible with endothelial cells releasing ATP in response to mechanical stimulation, P2X(2/3) receptor antagonists eliminated SIEH. The endothelium also appears to contribute to hyperalgesia in two ergonomic pain models (eccentric exercise and hindlimb vibration) and in a model of endometriosis. We propose that SIEH is produced by an effect of ET-1 on vascular endothelial cells, sensitizing its release of ATP in response to mechanical stimulation; ATP in turn acts at the nociceptor P2X(2/3) receptor.
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Neuroscience letters · Feb 2013
The effects of menthol on cold allodynia and wind-up-like pain in upper limb amputees with different levels of phantom limb pain.
The mechanisms underlying phantom limb pain are not fully known, but hypersensitivity appears to be a central element. Menthol has previously been suggested as a model for hypersensitivity, but it has not yet been investigated if different levels of neuropathic pain may influence the effects of menthol or if topical application of menthol may act as a model for hypersensitivity in patients with phantom limb pain. In the present study, menthol (l-menthol 40%) was applied to the affected and non-affected sides in 24 upper-limb amputees with different levels of phantom limb pain to test if menthol could induce cold allodynia and exacerbate wind-up-like pain. ⋯ After application of menthol, the level of phantom limb pain was only related to wind-up-like pain following brush (P=0.011) but not pinprick stimulation (P=0.233). This study indicates that menthol does influence hypersensitivity in phantom limb pain patients, and it is the first study to show that menthol may exacerbate wind-up-like pain in this group of neuropathic pain patients. The findings suggest that menthol may act as a model for studying sensitization in phantom limb patients.
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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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Anesthesia and analgesia · Feb 2013
Glycogen synthase kinase-3β contributes to remifentanil-induced postoperative hyperalgesia via regulating N-methyl-D-aspartate receptor trafficking.
Although remifentanil provides perfect analgesia during surgery, postoperative hyperalgesia after remifentanil administration might be a challenge to anesthesiologists. The trafficking and activation of N-methyl-D-aspartate (NMDA) receptors have a pivotal role in the development and maintenance of remifentanil-induced postoperative hyperalgesia. However, the underlying mechanisms of hyperalgesia are poorly elucidated. We designed the present study to examine the hypothesis that glycogen synthase kinase (GSK)-3β could contribute to remifentanil-induced postoperative hyperalgesia via regulating NMDA receptor trafficking in the spinal cord. ⋯ The above results suggest that activation of GSK-3β contributes to remifentanil-induced postoperative hyperalgesia via regulating NMDA receptor subunits (NR1 and NR2B) trafficking in the spinal cord. Inhibition of GSK-3β may be an effective novel option for the treatment of remifentanil-induced postoperative hyperalgesia.
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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.