Green light analgesia in mice is mediated by visual activation of enkephalinergic neurons in the ventrolateral geniculate nucleus

Green light exposure has been shown to reduce pain in animal models. Here, we report a vision-associated enkephalinergic neural circuit responsible for green light–mediated analgesia. Full-field green light exposure at an intensity of 10 lux produced analgesic effects in healthy mice and in a model of arthrosis. Ablation of cone photoreceptors completely inhibited the analgesic effect, whereas rod ablation only partially reduced pain relief. The analgesic effect was not modulated by the ablation of intrinsically photosensitive retinal ganglion cells (ipRGCs), which are atypical photoreceptors that control various nonvisual effects of light. Inhibition of the retino–ventrolateral geniculate nucleus (vLGN) pathway completely abolished the analgesic effects. Activation of this pathway reduced nociceptive behavioral responses; such activation was blocked by the inhibition of proenkephalin (Penk)–positive neurons in the vLGN (vLGNPenk). Moreover, green light analgesia was prevented by knockdown of Penk in the vLGN or by ablation of vLGNPenk neurons. In addition, activation of the projections from vLGNPenk neurons to the dorsal raphe nucleus (DRN) was sufficient to suppress nociceptive behaviors, whereas its inhibition abolished the green light analgesia. Our findings indicate that cone-dominated retinal inputs mediated green light analgesia through the vLGNPenk-DRN pathway and suggest that this signaling pathway could be exploited for reducing pain. Description Green light–induced analgesia in mice is mediated by a light-activated subpopulation of neurons in the ventrolateral geniculate nucleus. Pain relief gets the green light Pain relief gets the green lightExposure to green light exerts analgesic effects in rodents by activating a subpopulation of neurons in the ventrolateral geniculate nucleus (vLGN). Exposure to green light has been shown to reduce pain sensation in rodents, however, the mechanisms remain to be completely elucidated. Here, Tang et al. performed mechanistic studies in rodents and showed that cone and rod photoreceptor-mediated activation of neurons expressing proenkephalin in the vLGN mediated the analgesic effect of green light by modulating the activity of the dorsal raphe nucleus (DRN). The vLGN-DRN circuit is thus a potential target for reducing pain. ---MM