Transdermal tibial nerve optogenetic stimulation targeting C-fibers.

To explore whether stimulation of C-fibers in tibial nerves can induce bladder inhibition by optogenetic transdermal illumination. Ten rats were injected with AAV2/6-hSyn-ChR2(H134R)-EYFP into the tibial nerves. Transurethral cystometry was performed 4 weeks after the virus injection. Illumination (473-nm blue light at 100 mW) was performed with the fiber positioned above the right hind paw near the ankle. The light transmission efficiency was examined with a laser power meter. The effects on cystometry were compared before and after illumination with the bladder infused with normal saline and acetic acid, respectively. Upon transdermal delivery of 473-nm light at a peak power of 100 mW, the irradiance value of 0.653 mW/mm2 at the target region was detected, which is sufficient to activate opsins. The photothermal effect of 473-nm light is unremarkable. Acute inhibitory responses were not observed during stimulation regarding any of the bladder parameters; whereas, after laser illumination for 30 min, a statistically significant increase in bladder capacity with the bladder infused with normal saline (from 0.53 ± 0.04 mL to 0.72 ± 0.05 mL, < 0.001) and acetic acid (from 0.25 ± 0.02 mL to 0.37 ± 0.04 mL, < 0.001) was detected. A similar inhibitory response was observed with pulsed illumination at both 10Hz and 50Hz. However, illumination did not significantly influence base pressure, threshold pressure, or peak pressure. In this preliminary study, it can be inferred that the prolonged bladder inhibition is mediated by the stimulation of C-fibers in the tibial nerves, with no frequency-dependent characteristics. Although the 473-nm blue light has limited penetration efficacy, it is sufficient to modulate bladder functions through transdermal illumination on the superficial peripheral nervous system.