title: Reversible Induction of Pain Hypersensitivity following Optogenetic Stimulation of Spinal Astrocytes.
abstract: While glial activation is an integral part of pain pathogenesis, the existence of a causal relationship between glia and pain processing has yet to be demonstrated in vivo. Here, we have investigated whether the activation of spinal astrocytes could directly evoke pain hypersensitivity in vivo via the use of optogenetic techniques. Optogenetic stimulation of channelrhopdopsin-2 (ChR)-expressing spinal astrocytes induced pain hypersensitivity in a reversible and time-dependent manner, which was accompanied by glial activation, NR1 phosphorylation, ATP release, and the production of proalgesic mediators. Photostimulation of ChR2-expressing astrocytes in culture and spinal slices recapitulated in vivo findings, demonstrating the release of proalgesic mediators and electrophysiological disinhibition of spinal projection neurons. These findings deepen our understanding of the role of astrocytes in pain pathogenesis and provide the scientific basis for an astrocyte-oriented pain treatment.
authors.affiliation: Department of Pharmacology, Brain Science & Engineering Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu 41944, Republic of Korea.
authors.forename: Youngpyo
authors.initials: Y
authors.lastname: Nam
authors.affiliation: Department of Pharmacology, Brain Science & Engineering Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu 41944, Republic of Korea.
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Brain Science & Engineering Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu 41944, Republic of Korea.
authors.forename: Jong-Heon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Brain Science & Engineering Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu 41944, Republic of Korea.
authors.forename: Mithilesh Kumar
authors.initials: MK
authors.lastname: Jha
authors.affiliation: Department of Pharmacology, Brain Science & Engineering Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu 41944, Republic of Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Jung
authors.affiliation: Department of Pharmacology, Brain Science & Engineering Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu 41944, Republic of Korea.
authors.forename: Maan-Gee
authors.initials: MG
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 41940, Republic of Korea.
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Choi
authors.affiliation: Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 41940, Republic of Korea.
authors.forename: Il-Sung
authors.initials: IS
authors.lastname: Jang
authors.affiliation: Department of Anesthesiology and Pain Medicine, Kyungpook National University School of Medicine, Daegu 41944, Republic of Korea.
authors.forename: Dong Gun
authors.initials: DG
authors.lastname: Lim
authors.affiliation: Department of Anatomy, Kyungpook National University School of Medicine, Daegu 41944, Republic of Korea.
authors.forename: Sung-Hun
authors.initials: SH
authors.lastname: Hwang
authors.affiliation: Department of Anatomy, Kyungpook National University School of Medicine, Daegu 41944, Republic of Korea.
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Department of Pharmacology, Brain Science & Engineering Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu 41944, Republic of Korea. Electronic address: ksuk@knu.ac.kr.
authors.forename: Kyoungho
authors.initials: K
authors.lastname: Suk
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics; D009457:Neuroglia / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D062308:Optogenetics; D010146:Pain / Q000235:genetics* / Q000503:physiopathology; D012243:Rhodopsin / Q000235:genetics*; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology
chemical_list: D009419:Nerve Tissue Proteins; D000255:Adenosine Triphosphate; D012243:Rhodopsin
keywords: astrocytes; central sensitization; neuroinflammation; optogenetics; pain; spinal cord