TY - JOUR
T1 - A spinal microglia population involved in remitting and relapsing neuropathic pain
AU - Kohno, Keita
AU - Shirasaka, Ryoji
AU - Yoshihara, Kohei
AU - Mikuriya, Satsuki
AU - Tanaka, Kaori
AU - Takanami, Keiko
AU - Inoue, Kazuhide
AU - Sakamoto, Hirotaka
AU - Ohkawa, Yasuyuki
AU - Masuda, Takahiro
AU - Tsuda, Makoto
N1 - Funding Information:
This work was supported by the Japanese Society for the Promotion of Science (JSPS KAKENHI grants JP19H05658 and JP20H05900 to M.T.; JP20K22687, JP21H02752, and JP21H00204 to T.M.; and JP16H06280 to H.S.); the Japan Science and Technology Agency [JST Moonshot R&D grant JPMJMS2024 to M.T. and a Grant-in-Aid for Scientific Research on Innovative Areas - Platforms for Advanced Technologies and Research Resources “Advanced Bioimaging Support (ABiS)” to H.S.]; CREST (AMED grant JP21gm0910006 to M.T.; AMED grant JP20gm6310016 AMED-PRIME JP21wm0425001 to T.M.); the Platform Project for Supporting Drug Discovery and Life Science Research (BINDS AMED grant JP21am0101091 to M.T.); and by an academic research grant from Shionogi & Co., Ltd.
Publisher Copyright:
Copyright © 2022 The Authors.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - Neuropathic pain is often caused by injury and diseases that affect the somatosensory system. Although pain development has been well studied, pain recovery mechanisms remain largely unknown. Here, we found that CD11c-expressing spinal microglia appear after the development of behavioral pain hypersensitivity following nerve injury. Nerve-injured mice with spinal CD11c+ microglial depletion failed to recover spontaneously from this hypersensitivity. CD11c+ microglia expressed insulin-like growth factor-1 (IGF1), and interference with IGF1 signaling recapitulated the impairment in pain recovery. In pain-recovered mice, the depletion of CD11c+ microglia or the interruption of IGF1 signaling resulted in a relapse in pain hypersensitivity. Our findings reveal a mechanism for the remission and recurrence of neuropathic pain, providing potential targets for therapeutic strategies.
AB - Neuropathic pain is often caused by injury and diseases that affect the somatosensory system. Although pain development has been well studied, pain recovery mechanisms remain largely unknown. Here, we found that CD11c-expressing spinal microglia appear after the development of behavioral pain hypersensitivity following nerve injury. Nerve-injured mice with spinal CD11c+ microglial depletion failed to recover spontaneously from this hypersensitivity. CD11c+ microglia expressed insulin-like growth factor-1 (IGF1), and interference with IGF1 signaling recapitulated the impairment in pain recovery. In pain-recovered mice, the depletion of CD11c+ microglia or the interruption of IGF1 signaling resulted in a relapse in pain hypersensitivity. Our findings reveal a mechanism for the remission and recurrence of neuropathic pain, providing potential targets for therapeutic strategies.
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U2 - 10.1126/science.abf6805
DO - 10.1126/science.abf6805
M3 - Article
C2 - 35357926
AN - SCOPUS:85127389958
SN - 0036-8075
VL - 376
SP - 86
EP - 90
JO - Science
JF - Science
IS - 6588
ER -