Role of TRPV1 in augmentation of cerebral blood flow by cervical spinal cord stimulation in rats

Clinical experimental studies have indicated that upper cervical spinal cord stimulation (SCS) produces a significant increase in cerebral blood flow (CBF). However, the underlying mechanisms remain unclear. The aim of this study was to examine whether transient receptor potential vanilloid type 1 (TRPV1) was involved in the effects of SCS on CBF in rats. A spring‐loaded unipolar ball electrode was placed on the left dorsal column at cervical spinal cord (C1‐C2) in pentobarbital anesthetized, ventilated and paralyzed male rats. SCS with stimulus parameters (50 Hz, 0.2 ms, and 90% of motor threshold) was applied. Parietal craniotomy was performed to expose the left cortex for placement of laser Doppler flowmetry probe to measure CBF. Results showed that SCS increased CBF by 63.1±6.3% (P<0.01, n=24). Spinal transections at C6‐C7 segments did not affect SCS‐induced augmentation of CBF (53.8±11.7% vs 42.1±14.2%, n=7, P>0.05). Capsazepine (3 mg/kg, i.v.), an antagonist of TRPV1, reduced CBF‐responses to SCS from 68.5±12.5% to 27.5±12.8% (n=8, P<0.05). After desensitization of TRPV1‐containing fibers with resiniferatoxin (2 μg/kg, i.v), an ultra potent analog of capsaicin, SCS‐induced augmentation of CBF decreased from 65.0±9.5% to 27.4±7.2% (n=9, p<0.05). These data suggested that SCS‐induced augmentation of CBF was mediated by TRPV1. (NIH grants: HL‐075524 and NS‐035471)