Cutaneous vasodilation during dorsal column stimulation is mediated by dorsal roots and CGRP

Dorsal column stimulation (DCS) is used clinically to provide pain relief from peripheral vascular disease and has the benefit of increasing cutaneous blood flow to the affected lower extremities. The purpose of this study was to examine the role of dorsal roots, calcitonin gene-related peptide (CGRP), and substance P in the cutaneous vasodilation induced by DCS. Male rats were anesthetized with pentobarbital sodium (60 mg/kg ip). A unipolar ball electrode was placed unilaterally on the spinal cord at the L₁-L₂ spinal segment. Blood flow was recorded in each hindpaw foot pad with laser Doppler flowmeters. Blood flow responses were assessed during 1 min of DCS (either 0.2 mA subdural or 0.6 mA epidural at 50 Hz, 0.2-ms pulse duration). Dorsal rhizotomy of L₃-L₅ (n = 5) abolished the cutaneous vasodilation to subdural DCS, whereas removal of T¹⁰-T¹² (n = 5) and T¹³-L₂ dorsal roots (n = 5) did not attenuate the DCS-induced vasodilation. The CGRP antagonist, CGRP-(837) (2.6 mg/kg iv, n = 7), eliminated the epidural DCS-induced vasodilation, whereas the substance P receptor antagonist, CP-96345 (1 mg/kg iv, n = 6), had no effect. In summary, L₃-L₅ dorsal roots and CGRP are essential for the DCS-induced vasodilation. We propose that DCS antidromitally activates afferent fibers in the dorsal roots, thus causing peripheral release of CGRP, which produces cutaneous vasodilation.