Differential modulation of excitatory and inhibitory populations of superficial dorsal horn neurons in lumbar spinal cord by Aß-fiber electrical stimulation

Activation of Aß-fibers is fundamental to numerous analgesic therapies, yet its effects on dorsal horn neuronal activity remain unclear. We used multiphoton microscopy of the genetically encoded calcium indicator GCaMP6s to characterize the effects of Aß-fiber electrical stimulation (Aß-ES) on neural activity. Specifically, we quantified somatic responses evoked by C-fiber intensity stimulation before and after a 10-minute train of dorsal root Aß-ES in superficial dorsal horn (SDH) neurons, in mouse lumbar spinal cord. Aß-ES did not alter C-fiber-evoked activity when GCaMP6s was virally expressed in all neurons, in an intact lumbar spinal cord preparation. However, when we restricted the expression of GCaMP6s to excitatory or inhibitory populations, we observed that Aß-ES modestly potentiated evoked activity of excitatory neurons and depressed that of inhibitory neurons. Aß-ES had no significant effects in a slice preparation in either SDH population. A larger proportion of SDH neurons was activated by Aß-ES when delivered at a root rostral or caudal to the segment where the imaging and C-fiber intensity stimulation occurred. Aß-ES effects on excitatory and inhibitory populations depended on the root used. Our findings suggest that Aß-ES differentially modulates lumbar spinal cord SDH populations in a cell type- and input-specific manner. Furthermore, they underscore the importance of the Aß-ES delivery site, suggesting that Aß stimulation at a segment adjacent to where the pain is may improve analgesic efficacy.