%0 Journal Article %A Ihab Daou %A Hélène Beaudry %A Ariel R. Ase %A Jeffrey S. Wieskopf %A Alfredo Ribeiro-da-Silva %A Jeffrey S. Mogil %A Philippe Séguéla %T Optogenetic silencing of Nav1.8-positive afferents alleviates inflammatory and neuropathic pain %D 2016 %R 10.1523/ENEURO.0140-15.2016 %J eneuro %P ENEURO.0140-15.2016 %X We report a novel transgenic mouse model in which the terminals of peripheral nociceptors can be silenced optogenetically with high spatio-temporal 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 non-peptidergic nociceptors and yellow light stimulation reliably blocked electrically-induced action potentials in DRG neurons. Acute transdermal illumination of the hind paw 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 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 post-stimulation 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. Taken 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.Significance Statement: Selective activation and/or inhibition of peripheral nociceptors allow us to control pain transmission and modulate pain perception. Here, we generated a novel transgenic mouse line in which optical activation of archaerhodopsin-3 (Arch) proton pumps efficiently silenced the activity of Nav1.8+ nociceptive afferents. Acute and prolonged transdermal illumination of the hind paws of Nav1.8-Arch+ mice reduced mechanical and thermal hypersensitivity under inflammatory and neuropathic conditions, underlining the contribution of the peripheral neuronal component, particularly Nav1.8+ fibers, in the transmission of evoked pain as well as the development and maintenance of chronic pain. This optogenetic approach can be applied to functionally investigate other subsets of sensory neurons with high temporal precision, and safe genetic delivery of inhibitory opsins may prove useful for clinical applications. %U https://www.eneuro.org/content/eneuro/early/2016/02/25/ENEURO.0140-15.2016.full.pdf