title: Microglial P2Y12 receptors regulate microglial activation and surveillance during neuropathic pain.
abstract: Microglial cells are critical in the pathogenesis of neuropathic pain and several microglial receptors have been proposed to mediate this process. Of these receptors, the P2Y12 receptor is a unique purinergic receptor that is exclusively expressed by microglia in the central nervous system (CNS). In this study, we set forth to investigate the role of P2Y12 receptors in microglial electrophysiological and morphological (static and dynamic) activation during spinal nerve transection (SNT)-induced neuropathic pain in mice. First, we found that a genetic deficiency of the P2Y12 receptor (P2Y12(-/-) mice) ameliorated pain hypersensitivities during the initiation phase of neuropathic pain. Next, we characterised both the electrophysiological and morphological properties of microglia in the superficial spinal cord dorsal horn following SNT injury. We show dramatic alterations including a peak at 3days post injury in microglial electrophysiology while high resolution two-photon imaging revealed significant changes of both static and dynamic microglial morphological properties by 7days post injury. Finally, in P2Y12(-/-) mice, these electrophysiological and morphological changes were ameliorated suggesting roles for P2Y12 receptors in SNT-induced microglial activation. Our results therefore indicate that P2Y12 receptors regulate microglial electrophysiological as well as static and dynamic microglial properties after peripheral nerve injury, suggesting that the microglial P2Y12 receptor could be a potential therapeutic target for the treatment of neuropathic pain.
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province 710032, PR China; Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Gu
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Ukpong B
authors.initials: UB
authors.lastname: Eyo
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Madhuvika
authors.initials: M
authors.lastname: Murugan
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Jiyun
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Sanjana
authors.initials: S
authors.lastname: Matta
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province 710032, PR China. Electronic address: hldong6@hotmail.com.
authors.forename: Hailong
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA. Electronic address: lwu@dls.rutgers.edu.
authors.forename: Long-Jun
authors.initials: LJ
authors.lastname: Wu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D055724:Electrophysiological Phenomena; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D036641:Microscopy, Fluorescence, Multiphoton; D009437:Neuralgia / Q000378:metabolism*; D059348:Peripheral Nerve Injuries / Q000378:metabolism*; D058925:Receptors, Purinergic P2Y12 / Q000172:deficiency / Q000378:metabolism*
chemical_list: D058925:Receptors, Purinergic P2Y12
keywords: 2-Photon imaging; Electrophysiology; Microglia; Neuropathic pain; P2Y12 receptor; Surveillance