Involvement of α7 nAChR subtype in rat oxaliplatin-induced neuropathy: Effects of selective activation

摘要: Oxaliplatin, unlike other platinum anticancer agents, has only mild toxic effects on the hematopoietic, urinary and gastrointestinal systems. Its dose-limiting side effect is neurotoxicity that may evolve to a neuropathic syndrome which difficult treat. In this study we treated rats with oxaliplatin (2.4 mg/kg/day intraperitoneally, for 3 weeks), observed expression levels of α7 nicotinic acetylcholine receptor (nAChR) subunit were dramatically decreased both in peripheral central nervous system. The repeated administration (30 mg/kg/day per os, weeks) (R)-ICH3, most active enantiomer novel nAChR agonist, PNU-282987 prevented down-regulation. On hand, agonists se up-regulated compared control. (R)-ICH3 significantly reduced oxaliplatin-dependent alterations pain threshold when noxious or non-noxious stimuli used. Further ex vivo analysis highlighted their neuroprotective dorsal root ganglia nerves. two did not prevent increase microglia cell number induced by Astrocyte density was enhanced agonist treatment spinal cord, thalamus somatosensory area 1 as opposed treatment. increased glial region-specific manner. summary, involved neuropathology reduce protect tissue concomitant activation. Since cells play role neuroprotection, an AChR-dependent modulation functions suggested distinguish rescue signals from pathological pain-mediating pathway.