Optogenetic modulation of peripheral nociceptive neurons with biocompatible optoelectronic implants

Hyperexcitability of peripheral sensory neurons plays a critical role in the development and maintenance of chronic pain. Pharmacological analgesics used in clinics reduce neuronal activity. They often come with non-negligible side effects. Optogenetic approaches can modulate neuronal activity and are attracting growing interest for therapeutic uses, but the delivery of light in different parts of the body requires the development of specific optoelectronic interfaces. We designed and produced a microfabricated optoelectronic implant to deliver yellow light (559 nm) onto the sciatic nerve. We have surgically implanted the device in transgenic mice expressing the yellow light-sensitive inhibitory archaerhodopsin (ArchT) in nociceptive neurons. Yellow light induced a significant reduction in the responses of the nociceptive neurons and curbed the behavioral responses to noxious mechanical and thermal stimuli. Remarkably, the yellow light-related inhibition did not alter the behavioral responses evoked by innocuous mechanical stimulation or by intense inflammation. The optoelectronic implants showed reliable and reproducible opto-electrical performance. For stimulation parameters used in vivo (3.3 V, 60-80 mW/mm², 20 s train pulses, 1 Hz, 80% duty-cycle, and an inter-train interval of 1 s), limited temperature increase was measured in an environment mimicking neural tissue surrounded by muscle and fat. Similarly, the basal sensitivity of the implanted mice remains comparable to non-implanted mice, suggesting a safe integration of the soft electronic device. Our study confirmed that optoelectronic implants tailored to the sciatic nerve can provide specific light spectra and intensities at adequate levels for the optogenetic actuator to trigger significant electrophysiological and behavioral responses in pain perception.