Multiple spinal mediators in parenteral nicotine-induced antinociception

The role of spinal mechanisms in subcutaneous (s.c.) nicotine-induced antinociception was examined in male Sprague-Dawley rats using the hot-plate and tail-flick tests. Nicotine (0.125, 0.25, 0.375 or 0.5 mg/kg s.c.) produced a dose-related inhibition of nociception in both tests. Although increasing negative geotaxis response times slightly, no significant alteration of other motor reflexes was observed with 0.375 mg/kg of s.c. nicotine. Microinjection of 7 nmol of the high-affinity choline uptake inhibitor hemicholinium-3 into the rostral ventral medulla completely inhibited the antinociception produced by 0.375 mg/kg of s.c. nicotine. Intrathecal (i.t.) injection of 61 nmol of nicotine (in 10 microliter buffer) produced no changes in hot-plate or tail-flick test response latencies. Nicotine-induced antinociception was blocked by a variety of i.t. antagonists injected 12 min before s.c. injection of 0.375 mg/kg of nicotine. In both tests, i.t. pretreatment with 0.1 mumol (in 10 microliter buffer) of scopolamine, methysergide, yohimbine, idazoxan, mecamylamine or 0.2 mumol of atropine attenuated nicotine-induced increases in test response latencies. Pretreatment with 0.1 mumol of atropine attenuated nicotine-induced increases in tail-flick test, but not in the hot-plate test. Pretreatment with 0.1 mumol of i.t. prazosin or naloxone produced no changes in nicotine-induced increases in test response latencies in either test. These data suggest that the antinociception produced by s.c. nicotine is mediated via a number of sites in the spinal cord, including alpha-2 adrenergic, serotonergic and muscarinic cholinergic.(ABSTRACT TRUNCATED AT 250 WORDS)