Effects of dorsal rhizotomy on depressor response to spinal cord stimulation mediated by endogenous calcitonin gene-related peptide in the pithed rat.

Abstract

The effects of acute and chronic dorsal rhizotomy on vasodilation induced by spinal cord stimulation were investigated in the pithed rat in vivo. Pithed rats were treated intravenously with hexamethonium (2 mg/kg/min) to block autonomic outflow, and mean arterial blood pressure was maintained at approximately 100 mm Hg with methoxamine (10 to 15 micrograms/kg/min). Electrical stimulation (2 or 4 Hz, 10 V, 1 msec) of the lower thoracic spinal cord (T9-12) via the pithing rod caused a frequency-dependent depressor response without a change in heart rate. The depressor response to spinal cord stimulation was inhibited by the intravenous administration of human calcitonin gene-related peptide (CGRP) [8-37] (60 nmol/kg/min) or tetrodotoxin (100 micrograms/kg). In the pithed rat with acute or chronic bilateral dorsal root rhizotomy at lower thoracic levels (T8-12), spinal cord stimulation at 2 and 4 Hz caused no depressor response. These results suggest that the depressor response to spinal cord stimulation is mediated by endogenous CGRP, which is released from CGRP-containing nerves. The present results also suggest an outflow of CGRP-containing nerves from the spinal cord via the dorsal roots.