Analgesic action of nicotine on tibial nerve transection (TNT)-induced mechanical allodynia through enhancement of the glycinergic inhibitory system in spinal cord.
The activation of cholinergic pathways by nicotine elicits various physiological and pharmacological effects in mammals. For example, the stimulation of nicotinic acetylcholine receptors (nAChRs) leads to an antinociceptive effect. However, it remains to be elucidated which subtypes of nAChR are involved in the antinociceptive effect of nicotine on nerve injury-induced allodynia and the underlying cascades of the nAChR-mediated antiallodynic effect. In this study, we attempted to characterize the actions of nicotine at the spinal level against mechanical allodynia in an animal model of neuropathic pain, tibial nerve transection (TNT) in rats. It was found that the intrathecal injection of nicotine, RJR-2403, a selective alpha4beta2 nAChR agonist, and choline, a selective alpha7 nAChR agonist, produced an antinociceptive effect on the TNT-induced allodynia. The actions of nicotine were almost completely suppressed by pretreatment with mecamylamine, a non-selective nicotinic antagonist, or dihydro-beta-erythroidine, a selective alpha4beta2 nAChR antagonist, and partially reversed by pretreatment with methyllycaconitine, a selective alpha7 nAChR antagonist. Furthermore, pretreatment with strychnine, a glycine receptor antagonist, blocked the antinociception induced by nicotine, RJR-2403, and choline. On the other hand, the GABAA antagonist bicuculline did not reverse the antiallodynic effect of nicotine. Together, these results indicate that the alpha4beta2 and alpha7 nAChR system, by enhancing the activities of glycinergic neurons at the spinal level, exerts a suppressive effect on the nociceptive transduction in neuropathic pain.
Abdin
Md Joynal
MJ
Department of Dental Pharmacology, Division of Integrated Medical Science, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Morioka
Norimitsu
N
Morita
Katsuya
K
Kitayama
Tomoya
T
Kitayama
Shigeo
S
Nakashima
Toshikatsu
T
Dohi
Toshihiro
T
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002794:Choline / Q000494:pharmacology; D006930:Hyperalgesia / Q000188:drug therapy*; D007278:Injections, Spinal; D008297:Male; D009538:Nicotine / Q000031:analogs & derivatives / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013979:Tibial Nerve / Q000502:physiology; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000700:Analgesics; C579165:Chrna7 protein, rat; D018733:Nicotinic Antagonists; D018009:Receptors, Glycine; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; C012419:metanicotine; D009538:Nicotine; D002794:Choline