title: Central terminals of nociceptors are targets for nicotine suppression of inflammation.
abstract: Spinal intrathecal administration of nicotine inhibits bradykinin-induced plasma extravasation, a component of the inflammatory response, in the knee joint of the rat in a dose-related fashion. Nociceptors contain nicotinic receptors and activation of a nociceptor at its peripheral terminal, by capsaicin, also produces inhibition of inflammation. Therefore the aim of this study was to test the hypothesis that the spinal target for this effect of nicotine is the central terminal of the primary afferent nociceptor. Intrathecal administration of the neurokinin-1 receptor antagonist, (3aR,7aR)-7,7-diphenyl-2-(1-imino-2(2-methoxyphenyl)-ethyl) perhydroisoindol-4-1 hydrochloride or the N-methyl-D-aspartate receptor antagonist, DL-2-amino-5-phosphonovaleric acid, both antagonists of the action of primary afferent neurotransmitters, markedly attenuated the inhibition of bradykinin-induced plasma extravasation produced by both intrathecal nicotine and intraplantar capsaicin.Conversely, intrathecal administration of an alpha-adrenoceptor antagonist, phentolamine or an opioid receptor antagonist, naloxone, to block descending antinociceptive controls, which provide inhibitory input to primary afferent nociceptors, enhanced the action of both nicotine and capsaicin. These findings support the hypothesis that the central terminal of the primary afferent nociceptor is a CNS target at which nicotine acts to inhibit inflammation.
authors.affiliation: NIH Pain Center UCSF, University of California at San Francisco, Schools of Medicine and Dentistry, 521 Parnassus Avenue, 94143-0440, San Francisco, CA, USA.
authors.forename: F J P
authors.initials: FJ
authors.lastname: Miao
authors.forename: P G
authors.initials: PG
authors.lastname: Green
authors.forename: N
authors.initials: N
authors.lastname: Benowitz
authors.forename: J D
authors.initials: JD
authors.lastname: Levine
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D007719:Knee Joint / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D009538:Nicotine / Q000494:pharmacology / Q000627:therapeutic use*; D009619:Nociceptors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism
chemical_list: D009292:Narcotic Antagonists; D064729:Neurokinin-1 Receptor Antagonists; D011978:Receptors, Nicotinic; D009538:Nicotine