Role of Vagal Afferents and the Rostral Ventral Medulla in Intravenous Serotonin-Induced Changes in Nociception and Arterial Blood Pressure

THURSTON–STANFIELD, C. L., J. T. RANIERI, R. VALLABHAPURAPU AND D. BARNES–NOBLE. Role of vagal afferents and the rostral ventral medulla in intravenous serotonin-induced changes in nociception and arterial blood pressure. PHYSIOL BEHAV 67(5) 753–767, 1999.—Intravenous administration of serotonin inhibits the nociceptive tail-flick (TF) reflex, partially through activation of vagal afferents. The present study examined the role of the rostral ventral medulla (RVM) in i.v. serotonin-produced inhibition of the TF reflex. In Experiment 1, the effects of anesthetic blockade of the RVM on serotonin-produced inhibition of the TF were determined. Lidocaine attenuated the serotonin-produced inhibition of the TF reflex, but had no effect on the cardiovascular effects of serotonin. In Experiment 2, the effects of i.v. serotonin on neural activity in the RVM in intact and cardiopulmonary deafferented rats were determined. Neurons in the RVM were classified as ON and OFF cells, where ON cells were excited by noxious heat, and OFF cells were inhibited. The effects of i.v. serotonin on TF latency, blood pressure, and ON or OFF cell activity were then determined. In intact rats, serotonin produced a dose-dependent increase in TF latency, triphasic changes in blood pressure, and bi- or triphasic changes in ON or OFF cell activity. The changes in blood pressure included an initial sharp decrease in blood pressure (Bezold–Jarisch reflex), followed by a brief pressor response, followed by a delay depressor response. ON cells were generally excited, although there was a period during which the excitation decreased. OFF cells were initially excited, followed by a period of inhibition, followed by a second period of excitation. Bilateral cervical vagotomy attenuated the increase in TF latency, the Bezold–Jarisch reflex, and the excitation of OFF cells, and potentiated the excitation of ON cells and the pressor response. Bilateral sinoaortic deafferentation attenuated the Bezold–Jarisch reflex and potentiated the pressor response. These findings indicate that i.v. serotonin inhibits the TF reflex through at least two distinct mechansims, one of which requires the RVM. In addition, serotonin produces a vagally mediated excitation of OFF cells and inhibition of ON cells that may mediate some of the antinociception.