Vagal modulation of spinal nicotine-induced inhibition of the inflammatory response mediated by descending antinociceptive controls.
Noxious stimuli activate neuroendocrine axes, inhibiting inflammation, an effect that is powerfully attenuated by ongoing activity in subdiaphragmatic vagal afferents. To evaluate whether this inhibitory effect of vagal afferent activity is mediated by descending antinociceptive control, we tested whether antagonizing descending antinociceptive controls: (i) enhances the inhibition of inflammation produced by spinal nicotine (which stimulates central terminals of nociceptors) and (ii) occludes the enhancing effect of subdiaphragmatic vagotomy, in the rat. Spinal intrathecal co-administration of the alpha-adrenergic receptor antagonist phentolamine and the non-selective opioid receptor antagonist naloxone, and acute subdiaphragmatic vagotomy each produced enhancement, with similar magnitude, of nicotine-induced inhibition of plasma extravasation, produced by the potent inflammatory mediator, bradykinin. The combination of subdiaphragmatic vagotomy and intrathecal receptor antagonists, however, produced no further enhancement compared to each treatment alone. These findings support the suggestion that activity in descending antinociceptive controls modulates noxious stimulus-induced inhibition of inflammation and the vagal modulation of noxious stimulus-induced inhibition of inflammation is mediated by descending antinociceptive controls.
Miao
Frederick Jia-Pei
FJ
NIH Pain Center UCSF, University of California at San Francisco, Schools of Medicine and Dentistry, San Francisco, CA 94143-0440, USA.
Green
Paul
P
Benowitz
Neal
N
Levine
Jon D
JD
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D005070:Evans Blue / Q000378:metabolism; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D007278:Injections, Spinal / Q000379:methods; D007719:Knee Joint / Q000187:drug effects; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D010646:Phentolamine / Q000494:pharmacology; D010949:Plasma / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013119:Spinal Cord Injuries / Q000378:metabolism; D013268:Stimulation, Chemical; D014628:Vagotomy / Q000379:methods; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D004338:Drug Combinations; D009292:Narcotic Antagonists; D009270:Naloxone; D005070:Evans Blue; D009538:Nicotine; D001920:Bradykinin; D010646:Phentolamine