Nicotinic nociceptors on perivascular sensory nerve endings.

Intra-arterial injection of increasing doses of acetylcholine, nicotine, carbachol and pilocarpine into the pain reflex ear of the rabbit dose-dependently caused a reflex fall in mean arterial blood pressure. The order of potency of the algesic substances was: nicotine greater than acetylcholine much greater than carbachol much greater than pilocarpine, whereas the purely muscarinic agonist bethanechol was inactive up to 3 mg. Atropine at 1 microgram/ml did not influence the effect of acetylcholine. At 30 micrograms/ml it reduced the effect of acetylcholine but also that of bradykinin suggesting an unspecific action. Hexamethonium (1 microgram/ml) blocked the algesic effect of acetylcholine and nicotine without influencing that of bradykinin. Morphine, given systemically, blocked the algesic effect of acetylcholine and nicotine. Since nicotine showed the highest algesic potency (whereas bethanechol was inactive) and hexamethonium blocked the effect of acetylcholine and nicotine, the cholinergic "pain receptor" on sensory nerve endings is assumed to be of the nicotinic type.