Behavioral Evaluation of Transient Selective Neural Inhibition via Photobiomodulation (tSNIP)

Introduction: Current methods for treating pain often face significant limitations, including risk of addiction, limited efficacy, and undesirable systemic effects [1,2]. Consequently, there is a pressing need for alternative therapeutic approaches. Direct photobiomodulation (PBM) applied to nerves has emerged as a promising technique for selectively inhibiting action potential propagation in small-diameter axons [3]. This method, recently termed Transient Selective Neural Inhibition via PBM (tSNIP), demonstrates potential as a platform for novel therapies for patients experiencing persistent or pathological pain [4]. tSNIP has demonstrated reductions in small-fiber axon sensitivity in both human and animal models; however, precise dosing parameters must be established before full clinical translation can be achieved. This investigation aims to assess thresholds in applying tSNIP that are needed for treatment effectiveness by exploring the relationship between light parameters and physiologic outcomes.

Methods: This study evaluated tSNIP dosing paradigms by exploring parameters such as, irradiance at the nerve, energy at the nerve, duty cycle, and differing delivery techniques. Ultimately, the investigation also plans to assess different combinations of these variables to identify the most effective treatment protocols. This study utilized a capsaicin-induced nociceptive pain model in rats. Invasive tSNIP was applied by exposing the rat sciatic nerve, placing a cuff around the nerve connected to a fiber optic cable, and irradiating the nerve. Transcutaneous tSNIP was applied at the level of the ankle using a bare fiber tip. Behavioral experiments were conducted to determine reductions in small fiber thermal sensitivities.

Results: Analysis of results indicate that specific combinations of power, treatment duration and application style significantly reduce pain compared to control groups. Similar to previous results from our group, the higher power of emission reduces sensitivities most effectively compared to lower powers. Higher duty cycle administration also resulted in a greater reduction of hypersensitivities compared to the lower duty cycle using the same total energy (lower duty-cycle applied over a longer time).

Conclusion: These results indicate that tSNIP holds strong promise for future therapies. Future research should focus on further refinement of these dosing schemes and elucidation of the underlying mechanisms, with the goal of establishing standardized PBM protocols for transcutaneous, percutaneous, and implantable clinical applications.