Significance: Infrared (IR) inhibition can selectively block peripheral sensory nerve fibers, a potential treatment for autonomic-dysfunction-related diseases (e.g., neuropathic pain and interstitial cystitis). Lowering the IR inhibition threshold can increase its translational potentials.
Aim: Infrared induces inhibition by enhancing potassium channel activation. We hypothesized that the IR dose threshold could be reduced by combining it with isotonic ion replacement.
Approach: We tested the IR inhibition threshold on the pleural-abdominal connective of Aplysia californica. Using a customized chamber system, the IR inhibition was applied either in normal saline or in isotonic ion-replaced saline, which could be high glucose saline, high choline saline, or high glucose/high choline saline. Each modified saline was at a subthreshold concentration for inhibiting neural conduction.
Results: We showed that isotonically replacing ions in saline with glucose and/or choline can reduce the IR threshold and temperature threshold of neural inhibition. Furthermore, the size selectivity of IR inhibition was preserved when combined with high glucose/high choline saline.
Conclusions: The present work of IR inhibition combined with isotonic ion replacement will guide further development of a more effective size-selective IR inhibition modality for future research and translational applications.
Neuromodulation has the potential to treat various diseases (i.e., heart failure, obesity). Several clinical trials have recently failed because of the inability to modulate small-diameter fibers. Previously, we demonstrated preferential inhibition of small-diameter fibers using infrared neuromodulation (IRN). To understand the mechanism of action, we did a mathematical analysis which suggested that any modality acting primarily on the axonal surface would preferentially affect small-diameter axons. To test our hypothesis, we examined whether isotonic glucose solution would give results similar to IRN.
We stimulated the left and right pleural-abdominal connective nerves of Aplysia californica and recorded the resulting compound action potentials (CAPs). We designed a chamber with three isolated compartments through which the nerve passes sequentially. Aplysia saline is perfused in the two outer chambers while the middle chamber can be perfused with either Aplysia saline or an isotonic glucose solution (10.21 w/v %). The width of the middle chamber is adjustable to vary the length of nerve perfused by the isotonic glucose solution. As the length of the middle chamber increases, recorded CAPs are initially unaffected, then show a loss of peaks representing small-diameter axons, then show no activity. We can restore full, unchanged CAPs by washing out the glucose solution and replacing it with Aplysia saline. These results support the hypothesis that any modality (e.g., both IRN and isotonic glucose solution) acting primarily on the axonal surface would preferentially affect small-diameter axons. Future studies will compare IRN with isotonic glucose block.