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We hypothesize that development of cortical hyperexcitability underlying neuropathic pain may involve homeostatic plasticity in response to lesion-induced somatosensory deprivation and activity loss, and can be controlled by enhancing cortical activity. In a mouse model of neuropathic pain, <jats:italic>in vivo<\/jats:italic> two-photon imaging and patch clamp recording showed initial loss and subsequent recovery and enhancement of spontaneous firings of somatosensory cortical pyramidal neurons. Unilateral optogenetic stimulation of cortical pyramidal neurons both prevented and reduced pain-like behavior as detected by bilateral mechanical hypersensitivity of hindlimbs, but corpus callosotomy eliminated the analgesic effect that was ipsilateral, but not contralateral, to optogenetic stimulation, suggesting involvement of inter-hemispheric excitatory drive in this effect. Enhancing activity by focally blocking cortical GABAergic inhibition had a similar relieving effect on the pain-like behavior. Patch clamp recordings from layer V pyramidal neurons showed that optogenetic stimulation normalized cortical hyperexcitability through changing neuronal membrane properties and reducing frequency of excitatory postsynaptic events. We conclude that development of neuropathic pain involves abnormal homeostatic activity regulation of somatosensory cortex, and that enhancing cortical excitatory activity may be a novel strategy for preventing and controlling neuropathic pain.<\/jats:p>","DOI":"10.1038\/s41598-017-12972-6","type":"journal-article","created":{"date-parts":[[2017,10,2]],"date-time":"2017-10-02T10:25:27Z","timestamp":1506939927000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Enhancing excitatory activity of somatosensory cortex alleviates neuropathic pain through regulating homeostatic plasticity"],"prefix":"10.1038","volume":"7","author":[{"given":"Wenhui","family":"Xiong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingjie","family":"Ping","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S.","family":"Ripsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace Santa Cruz","family":"Chavez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi Elise","family":"Hannon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kewen","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhui","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaishnavi","family":"Jadhav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Chai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cungen","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1725-6881","authenticated-orcid":false,"given":"Huangan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianqiao","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1133-1174","authenticated-orcid":false,"given":"Armin","family":"Blesch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fletcher A.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,10,6]]},"reference":[{"key":"12972_CR1","doi-asserted-by":"crossref","unstructured":"van Hecke, O., Austin, S. 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