Laser and Viral Optogenetic Neuromodulation of Peripheral Nerve Pain in a Rodent Model

Abstract

Research Question: Can different pain responses be neuromodulated via optogenetic and optical stimulation?

Background: The opioid crisis in the United States is one of the most significant public health problems plaguing our country. Even with increased awareness through media and educational means, the problem is unfortunately worsening. Many individuals are dying from drug overdoses, and many of those overdose deaths can be attributed to opioids and opioid-like painkillers. There is a great need for an alternative to current pain medications.

Materials and Methods: Using a glutamic acid decarboxylase (GAD) promoter, our group delivered our highly sensitive optogenetic modulator Multi-Characteristic Opsin (MCO) to target inhibitory GABAergic Anterior Cingulate Cortex (ACC), Dorsal Root Ganglion (DRG), and spinal neurons in a rodent model. Opsin delivery was accomplished by both adeno-associated viral (AAV) vectors for optogenetic stimulation and functional gold nanorods for optical stimulation. Optogenetic stimulation was manipulated by a light source that delivered 630 nm red light, which our MCO was specific and sensitive to. We also controlled light delivery with a wireless phone application we created. The light’s frequency and intensity were handled through the wireless application. Acute pain responses were assessed via a formalin pain model. Neuropathic pain responses were evaluated via a sciatic nerve ligation model and Von Frey assays.

Results: Optogenetic stimulation decreased pain responses by a >60% threshold in both ACC and DRG models. During the early inflammatory phase of acute pain in response to formalin injection into the rodent’s hind paw, we saw a significant decrease in pain responses. There was no significant decrease in pain responses to our assay’s initial injection (nociceptive) portion. Our Von Frey assay demonstrated that our experimental groups had significantly decreased hind paw retraction, hind paw licking, and overall pain responses.

Conclusions: Overall, our experiments demonstrate that neuromodulation of GABAergic, pain-inhibiting pathways within the nervous system can be targeted to reduce multiple pain models, including inflammatory and neuropathic pain.