How spatial temperature gradients modulate infrared stimulation of the ex vivo rat sciatic nerve

Infrared neural stimulation (INS) uses transient near-infrared light to activate neuronal activity, likely through heat-induced thermal gradients. However, neither the effect of basal temperature nor heat accumulation has specifically been investigated. This study examines how spatial temperature gradients, varied by different laser repetition rates and the addition of a continuous wave laser, affect the elicitation of compound nerve action potentials (CNAPs). In addition, we investigate the role of basal temperature. Overall, our results indicate that CNAP generation is more influenced by the induced spatial temperature gradients than by the increase in local or basal temperature, or temperature build-up. For instance, low-power continuous wave laser combined with low repetition rate pulsed laser stimulation successfully induced CNAPs, whereas increasing the basal nerve temperature did not facilitate CNAP generation. A heat transfer model, consistent with the experimental data, confirms that, while the volume exposed to rapid temperature changes remains constant, heat accumulation increases spatial gradients with the number of stimulation pulses. This likely explains the progressive recruitment of nerve fibers and the observed increase in CNAP amplitude. Taken together, these results highlight the critical role of spatial temperature gradients in effective infrared neural stimulation, while a temperature threshold does not appear to be the primary mechanism in CNAP triggering.