Articles: hyperalgesia.
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Oxaliplatin and paclitaxel are commonly used anti-cancer drugs, but they frequently cause peripheral neuropathic pain. In this study, we investigated the effect of elcatonin, a synthetic eel calcitonin, on oxaliplatin- and paclitaxel-induced neuropathy in rats. The rats were treated with a single dose of oxaliplatin (6 mg/kg, i.p.) or repeated doses of paclitaxel (2 mg/kg, i.p.) on 4 alternate days. ⋯ Pre-administration of elcatonin almost completely prevented cold and mechanical allodynia from being induced by both compounds. These results suggest that elcatonin attenuates oxaliplatin- and paclitaxel-induced neuropathic pain by inhibiting the cellular signaling related to transient receptor potential ankyrin-1 and melastatin-8. Thus, we conclude that administration of elcatonin may improve the quality of life of cancer patients receiving chemotherapy.
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Neuropathic pain after nerve injuries is characterized by positive and negative sensory symptoms and signs. The extent of sensory fiber loss after nerve injuries has been demonstrated to correlate with symptoms of neuropathic pain by quantitative sensory testing and confirmed by biopsies of small nerve fibers. However, the relationship between the pathologic changes of large nerves on injuries and resulting pain symptoms remains unclear. ⋯ Transient injuries on sensory fibers can produce either positive or negative symptoms of neuropathic pain, and the different extent of sensory fiber loss after different degrees of injuries might account for the varied resulting symptoms of neuropathic pain.
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J. Physiol. Pharmacol. · Dec 2012
Exogenous melatonin abolishes mechanical allodynia but not thermal hyperalgesia in neuropathic pain. The role of the opioid system and benzodiazepine-gabaergic mechanism.
Melatonin (MT) is a neurohormone synthesized and secreted by the pineal gland. MT plays an important role in the regulation of physiological and neuroendocrine functions. The purpose of this study was to assess the overall effect of melatonin on neuropathic pain, the type of melatonin receptor involved, and potential role of the opioid system and GABA(A) receptors. ⋯ The antiallodynic effect of MT was also abolished by flumazenil and picrotoxin. Melatonin influences the mechanical allodynia but not thermal hyperalgesia via activation of opioid system and benzodiazepine-GABAergic pathway. Antinociceptive effects of melatonin are mostly related to the MT1/MT2 receptors interaction.
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The elusiveness of the mechanism underlying pain is a major impediment in developing effective clinical treatments. We examined whether the phosphorylation of spinal serum- and glucocorticoid-inducible kinase 1 (SGK1) and downstream glutamate receptor interacting protein (GRIP)-associated protein-1 (GRASP-1)/Rab4-dependent GluR1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) recycling play a role in inflammatory pain. After intraplantar injection of complete Freund's adjuvant (CFA), we assessed thermal hyperalgesia using the Hargreaves test and analyzed dorsal horn samples (L4-5) using Western blotting, coprecipitation, and immunofluorescence. ⋯ Intrathecal 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, an AMPAR antagonist, 1, 3, and 10 μM, 10 μL/rat) attenuated the hyperalgesia and GluR1 trafficking caused by CFA; however, it had no effect on SGK1 phosphorylation. Small interfering RNA targeting Rab4 hindered the CFA-induced hyperalgesia and the associated GluR1 trafficking and Rab4-GluR1 coprecipitation. Our results suggest that spinal SGK1 phosphorylation, which subsequently triggers the GRASP-1/Rab4 cascade, plays a pivotal role in CFA-induced inflammatory pain by regulating GluR1-containing AMPAR recycling in the dorsal horn.
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A connection between pain and depression has long been recognized in the clinical setting; however, its mechanism remains unclear. This study showed that mechanical hyperalgesia induced by unilateral temporomandibular joint (TMJ) inflammation was exacerbated in Wistar-Kyoto (WKY) rats with genetically predisposed depressive behavior. Reciprocally, TMJ inflammation enhanced depressive behavior such that a lower nociceptive threshold correlated with a higher score of depressive behavior in the same WKY rats. ⋯ Intracisternal administration of 6-chloromelatonin (250 μg, twice daily for 7 days) concurrently attenuated mechanical hyperalgesia and depressive behavior in WKY rats as well as downregulated the NR1 expression in the ipsilateral Sp5C. In patch-clamp recordings, melatonin dose-dependently decreased NMDA-induced currents in spinal cord dorsal horn substantia gelatinosa neurons. These results demonstrate a reciprocal relationship between TMJ inflammation-induced mechanical hyperalgesia and depressive behavior and suggest that the central melatoninergic system, through modulation of the NMDA receptor expression and activity, may play a role in the mechanisms of the comorbidity between pain and depression.