Optogenetic evaluation of the influence of gabaergic system in the antinociception induced by insular cortex electrical stimulation in neuropathic pain

Abstract

Neuropathic pain is one of the most rebellious conditions to the antalgic treatment, making the search for new effective therapies extremely urgent. Insular cortex is a new potential target for neuromodulation once it is closely involved in central pain integration and modulation and it is deeply affected in neuropathic pain states. We have recently demonstrated that electrical stimulation of the insular cortex induces antinociception in rats submitted to a neuropathic pain model, by mechanisms that involve the inhibition of neuronal activation in the anterior cingulate cortex (ACC) and the modulation of gabaergic system in the insula. Herein we aim to evaluate the influence of parvalbumin- positive (PV+) gabaergic inhibitory neurons in mechanical and thermal nociception as well as to analyze the presence of direct gabaergic projections from the posterior insula to the ACC. For this purpose, PV-Cre mice (Jackson Laboratories) submitted to a virus injection with AAV DIO ChR2-mCherry virus or AAV DIO Arch3-GFP will be submitted to optogenetics photostimulation in ACC (stereotaxic coordinates: +1.00 mm rostral to bregma; 0,25mm mediolateral left to the sagital fissure; 1,65 deep),and submitted to a digital plantar aesthesiometer and plantar test for mechanical and thermal sensitivity evaluation, respectively. The results to be demonstrated will consolidate the insular gabaergic influence on neuropathic pain modulation. (AU)