TY - JOUR
T1 - Controlled activation of cortical astrocytes modulates neuropathic pain-like behaviour
AU - Takeda, Ikuko
AU - Yoshihara, Kohei
AU - Cheung, Dennis L.
AU - Kobayashi, Tomoko
AU - Agetsuma, Masakazu
AU - Tsuda, Makoto
AU - Eto, Kei
AU - Koizumi, Schuichi
AU - Wake, Hiroaki
AU - Moorhouse, Andrew J.
AU - Nabekura, Junichi
N1 - Funding Information:
We thank M. Kano for the gift of Elvax beads; T. Toda, T. Kobayashi, T Oba for excellent technical assistance and critical discussions on the experiments; H. Hirase, H. Monai for technical advice of tDCS; M. Cooke for offering an analytical software for the open field test. Confocal images were acquired at the Spectrography and Bioimaging Facility, NIBB Core Research Facilities. This work was supported by a Core research for Evolutional Science and Technology (CREST) grant from the Japan Agency for Medical Research and Development (AMED) and from the Japan Science and Technology Agency (JST) (JPMJCR11S1, JPMJCR1755 and JPMJCR14G2, to J.N.); Grant-in-Aids for Scientific Research (A) (17H01530 and 20H00500, to J.N.) from the Japan Society for the Promotion of Science (JSPS); a research grant from Takeda Science Foundation (to J.N.); a research grant from Naito Foundation (to J.N.); Grant-in-Aid for Young Scientists (17K16133 and 20K16510, to I.T.) from JSPS; Grant-in-Aid for Transformative Research Areas (A) “ Inducing lifelong plasticity (iPlasticity) by brain rejuvenation “ (21H05688, to I.T.) from JSPS; a research grand from the Hori science and arts foundation (2600007301, to I.T.); Fostering Joint International Research (B) (20KK0170, to I.T.) from JSPS; KAKENHI Grant (20H05076 and 21H02801, to M.A.) from JSPS; Bilateral Programme (JPJSBP1-20199901, to M.A.) from JSPS; AMED (19dm0207086, to M.A.) from AMED. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.
Funding Information:
We thank M. Kano for the gift of Elvax beads; T. Toda, T. Kobayashi, T Oba for excellent technical assistance and critical discussions on the experiments; H. Hirase, H. Monai for technical advice of tDCS; M. Cooke for offering an analytical software for the open field test. Confocal images were acquired at the Spectrography and Bioimaging Facility, NIBB Core Research Facilities. This work was supported by a Core research for Evolutional Science and Technology (CREST) grant from the Japan Agency for Medical Research and Development (AMED) and from the Japan Science and Technology Agency (JST) (JPMJCR11S1, JPMJCR1755 and JPMJCR14G2, to J.N.); Grant-in-Aids for Scientific Research (A) (17H01530 and 20H00500, to J.N.) from the Japan Society for the Promotion of Science (JSPS); a research grant from Takeda Science Foundation (to J.N.); a research grant from Naito Foundation (to J.N.); Grant-in-Aid for Young Scientists (17K16133 and 20K16510, to I.T.) from JSPS; Grant-in-Aid for Transformative Research Areas (A) “ Inducing lifelong plasticity (iPlasticity) by brain rejuvenation “ (21H05688, to I.T.) from JSPS; a research grand from the Hori science and arts foundation (2600007301, to I.T.); Fostering Joint International Research (B) (20KK0170, to I.T.) from JSPS; KAKENHI Grant (20H05076 and 21H02801, to M.A.) from JSPS; Bilateral Programme (JPJSBP1-20199901, to M.A.) from JSPS; AMED (19dm0207086, to M.A.) from AMED. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Chronic pain is a major public health problem that currently lacks effective treatment options. Here, a method that can modulate chronic pain-like behaviour induced by nerve injury in mice is described. By combining a transient nerve block to inhibit noxious afferent input from injured peripheral nerves, with concurrent activation of astrocytes in the somatosensory cortex (S1) by either low intensity transcranial direct current stimulation (tDCS) or via the chemogenetic DREADD system, we could reverse allodynia-like behaviour previously established by partial sciatic nerve ligation (PSL). Such activation of astrocytes initiated spine plasticity to reduce those synapses formed shortly after PSL. This reversal from allodynia-like behaviour persisted well beyond the active treatment period. Thus, our study demonstrates a robust and potentially translational approach for modulating pain, that capitalizes on the interplay between noxious afferents, sensitized central neuronal circuits, and astrocyte-activation induced synaptic plasticity.
AB - Chronic pain is a major public health problem that currently lacks effective treatment options. Here, a method that can modulate chronic pain-like behaviour induced by nerve injury in mice is described. By combining a transient nerve block to inhibit noxious afferent input from injured peripheral nerves, with concurrent activation of astrocytes in the somatosensory cortex (S1) by either low intensity transcranial direct current stimulation (tDCS) or via the chemogenetic DREADD system, we could reverse allodynia-like behaviour previously established by partial sciatic nerve ligation (PSL). Such activation of astrocytes initiated spine plasticity to reduce those synapses formed shortly after PSL. This reversal from allodynia-like behaviour persisted well beyond the active treatment period. Thus, our study demonstrates a robust and potentially translational approach for modulating pain, that capitalizes on the interplay between noxious afferents, sensitized central neuronal circuits, and astrocyte-activation induced synaptic plasticity.
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UR - http://www.scopus.com/inward/citedby.url?scp=85134113154&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-31773-8
DO - 10.1038/s41467-022-31773-8
M3 - Article
C2 - 35835747
AN - SCOPUS:85134113154
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4100
ER -
