biostudies-literatureMichoud FSwiss National Science FoundationFondation BertarelliSir Henry Dale fellowship jointly funded by the Wellcome Trust and the Royal SocietyNINDS NIH HHSEuropean Union's Horizon 2020 reserach and innovation program under the Marie Sklodowska-Curie grant agreementWellcome Trust179-185https://www.ebi.ac.uk/biostudies/studies/S-EPMC7878280biostudies-literatureUnknown39(2)Activation of nociceptor sensory neurons by noxious stimuli both triggers pain and increases capillary permeability and blood flow to produce neurogenic inflammation^1,2, but whether nociceptors also interact with the immune system remains poorly understood. Here we report a neurotechnology for selective epineural optogenetic neuromodulation of nociceptors and demonstrate that nociceptor activation drives both protective pain behavior and inflammation. The wireless optoelectronic system consists of sub-millimeter-scale light-emitting diodes embedded in a soft, circumneural sciatic nerve implant, powered and driven by a miniaturized head-mounted control unit. Photostimulation of axons in freely moving mice that express channelrhodopsin only in nociceptors resulted in behaviors chaNature biotechnologyEpineural optogenetic activation of nociceptors initiates and amplifies inflammation.PMC7878280BSCGI0_1578000109372/Z/15/ZR35 NS105076Browne LEFurfaro IDoyle BLacour SPMoon RMichoud FBrun NGalan KHuang QAkouissi OWoolf CJJain ATetreault MZhang ZSeehus CSchonle PTalbot STaub DMeier PfalseEpineural optogenetic activation of nociceptors initiates and amplifies inflammation.Activation of nociceptor sensory neurons by noxious stimuli both triggers pain and increases capillary permeability and blood flow to produce neurogenic inflammation^1,2, but whether nociceptors also interact with the immune system remains poorly understood. Here we report a neurotechnology for selective epineural optogenetic neuromodulation of nociceptors and demonstrate that nociceptor activation drives both protective pain behavior and inflammation. The wireless optoelectronic system consists of sub-millimeter-scale light-emitting diodes embedded in a soft, circumneural sciatic nerve implant, powered and driven by a miniaturized head-mounted control unit. Photostimulation of axons in freely moving mice that express channelrhodopsin only in nociceptors resulted in behaviors cha2021-01-01T00:00:00Z2021 Feb2025-04-03T23:45:42.644Z2025-04-03T23:45:42.644ZS-EPMC78782803295895810.1038/s41587-020-0673-2