STIMULATORY PATHWAYS AND SITES OF ACTION OF INTRATHECALLY ADMINISTERED NICOTINIC AGENTS

Intrathecal (i.t.) administration of nicotinic agonists to rats elicit s a receptor-mediated pressor response, a heart rate increase and irri tation-nociceptive behavior. We examined the stimulatory pathways and sites of action of spinally administered nicotinic agonists. The thora cic region appears more sensitive to nicotine-elicited pressor actions than the lumbar or cervical regions of the spinal cord. Nicotinic rec eptors evoking a nociceptive response appear to be located over an are a extending from the lumbar rostrally to the thoracic region. Similar to the pressor response the thoracic spinal cord is the most sensitive region to nicotine in producing the heart rate increase. The cervical region is the least responsive to nicotine, suggesting sites of actio ns caudal to the brain stem. Intravenous infusion of trimethaphan inhi bited the nicotine-elicited pressor response and tachycardia without a ffecting the irritation response. This suggests that the cardiovascula r responses to spinal nicotinic agonists result from enhanced sympathe tic outflow. Intrathecal morphine and MK-801 block spinal nicotine-eli cited irritation and tachycardia but not the pressor response, indicat ing that pressor and irritation responses pressor and irritation respo nses involve independent receptor-mediated pathways. Tachycardia may b e associated with the irritation response. In contrast to nicotine, bo th pressor and irritation responses to cytisine were blocked by morphi ne with no effect on heart rate. Spinal transection at the T-1-2 level eliminated the nociceptive response to nicotine but not the pressor r esponse. Cytisine responses were similar to nicotine; however, cytisin e was significantly less potent as a pressor agent in the transected c ompared with intact animals. Hemi-cholinium-3 treatment did not affect the nicotine-evoked responses; however, cytisine-elicited pressor and heart rate responses were significantly reduced. Taken together, the data indicate that i.t. nicotinic agonists can elicit pressor and noci ceptive responses via discrete receptor-linked pathways. Cytisine stim ulation involves the spinobulbar pathway and direct stimulation of the preganglionic sympathetic neurons, whereas nicotine largely stimulate s preganglionic sympathetic neurons to enhance sympathetic outflow.