Quantitative characterization and spinal substrates of antinociception produced by electrical stimulation of the subdiaphragmatic vagus in rats.

Abstract

Physiological, chemical or electrical activation of vagal afferents produces antinociception in rats. The present study examined the effects of electrical stimulation of the subdiaphragmatic vagus (SDV) on the nociceptive tail-flick reflex, arterial blood pressure, and heart rate in rats lightly anesthetized with pentobarbital sodium. The intensity of SDV stimulation (20 Hz, 2 msec) necessary to inhibit the tail-flick reflex to a 10 sec cut-off latency for 3 consecutive trials was defined as the threshold to produce antinociception. Electrical stimulation of the SDV suppressed the tail-flick reflex in a linear, intensity-dependent manner. In addition, the threshold varied as a function of either the frequency or the pulse width of SDV stimulation, such that decreases in either frequency or pulse width, from 20 Hz and 2 msec, respectively, systematically increased the threshold current necessary to produce antinociception. SDV stimulation also produced modest decreases in heart rate (HR), but arterial blood pressure (ABP) responses were highly variable in both the magnitude and direction of change. Intrathecal administration of 30 micrograms of the serotonergic receptor antagonist methysergide significantly increased the threshold for antinociception produced by SDV stimulation from 80 to 938.8 microA, whereas 15 micrograms of methysergide had no significant effect. Intrathecal administration of saline, 30 micrograms of naloxone, or 30 micrograms of phentolamine had no significant effect on the threshold of SDV stimulation required to produce antinociception. Systemic administration of naloxone (4 mg/kg i.p. or i.v.) also had no effect on the antinociceptive threshold. Intrathecal administration of these receptor antagonists had no significant effect on the ABP and HR responses produced by electrical stimulation of the SDV at the threshold intensity producing antinociception.(ABSTRACT TRUNCATED AT 250 WORDS)