TY - JOUR T1 - Optogenetic Silencing of Na<sub>v</sub>1.8-Positive Afferents Alleviates Inflammatory and Neuropathic Pain JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0140-15.2016 VL - 3 IS - 1 SP - ENEURO.0140-15.2016 AU - Ihab Daou AU - Hélène Beaudry AU - Ariel R. Ase AU - Jeffrey S. Wieskopf AU - Alfredo Ribeiro-da-Silva AU - Jeffrey S. Mogil AU - Philippe Séguéla Y1 - 2016/01/01 UR - http://www.eneuro.org/content/3/1/ENEURO.0140-15.2016.abstract N2 - We report a novel transgenic mouse model in which the terminals of peripheral nociceptors can be silenced optogenetically with high spatiotemporal precision, leading to the alleviation of inflammatory and neuropathic pain. Inhibitory archaerhodopsin-3 (Arch) proton pumps were delivered to Nav1.8+ primary afferents using the Nav1.8-Cre driver line. Arch expression covered both peptidergic and nonpeptidergic nociceptors and yellow light stimulation reliably blocked electrically induced action potentials in DRG neurons. Acute transdermal illumination of the hindpaws of Nav1.8-Arch+ mice significantly reduced mechanical allodynia under inflammatory conditions, while basal mechanical sensitivity was not affected by the optical stimulation. Arch-driven hyperpolarization of nociceptive terminals was sufficient to prevent channelrhodopsin-2 (ChR2)-mediated mechanical and thermal hypersensitivity in double-transgenic Nav1.8-ChR2+-Arch+ mice. Furthermore, prolonged optical silencing of peripheral afferents in anesthetized Nav1.8-Arch+ mice led to poststimulation analgesia with a significant decrease in mechanical and thermal hypersensitivity under inflammatory and neuropathic conditions. These findings highlight the role of peripheral neuronal inputs in the onset and maintenance of pain hypersensitivity, demonstrate the plasticity of pain pathways even after sensitization has occurred, and support the involvement of Nav1.8+ afferents in both inflammatory and neuropathic pain. Together, we present a selective analgesic approach in which genetically identified subsets of peripheral sensory fibers can be remotely and optically inhibited with high temporal resolution, overcoming the compensatory limitations of genetic ablations. ER -