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We recently demonstrated that the spinal sigma non\u2010opioid intracellular receptor 1 (\u03c31 receptor) modulates p38 MAPK phosphorylation (p\u2010p38), which plays a critical role in the induction of <jats:styled-content style=\"fixed-case\">MA<\/jats:styled-content> in neuropathic rats. However, the histological and physiological relationships among \u03c31, p\u2010p38 and astrocyte activation is unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We investigated: (i) the precise location of \u03c31 receptors and p\u2010p38 in spinal dorsal horn; (ii) whether the inhibition of \u03c31 receptors or p38 modulates chronic constriction injury (<jats:styled-content style=\"fixed-case\">CCI<\/jats:styled-content>)\u2010induced astrocyte activation; and (iii) whether this modulation of astrocyte activity is associated with <jats:styled-content style=\"fixed-case\">MA<\/jats:styled-content> development in <jats:styled-content style=\"fixed-case\">CCI<\/jats:styled-content> mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The expression of \u03c31 receptors was significantly increased in astrocytes on day 3 following <jats:styled-content style=\"fixed-case\">CCI<\/jats:styled-content> surgery. Sustained intrathecal treatment with the \u03c31 antagonist, <jats:styled-content style=\"fixed-case\">BD<\/jats:styled-content>\u20101047, attenuated <jats:styled-content style=\"fixed-case\">CCI<\/jats:styled-content>\u2010induced increase in <jats:styled-content style=\"fixed-case\">GFAP<\/jats:styled-content>\u2010immunoreactive astrocytes, and the treatment combined with fluorocitrate, an astrocyte metabolic inhibitor, synergistically reduced the development of <jats:styled-content style=\"fixed-case\">MA<\/jats:styled-content>, but not thermal hyperalgesia. The number of p\u2010p38\u2010ir astrocytes and neurons, but not microglia was significantly increased. Interestingly, intrathecal <jats:styled-content style=\"fixed-case\">BD<\/jats:styled-content>\u20101047 attenuated the expression of p\u2010p38 selectively in astrocytes but not in neurons. Moreover, intrathecal treatment with a p38 inhibitor attenuated the <jats:styled-content style=\"fixed-case\">GFAP<\/jats:styled-content> expression, and this treatment combined with fluorocitrate synergistically blocked the induction of <jats:styled-content style=\"fixed-case\">MA<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Spinal \u03c31 receptors are localized in astrocytes and blockade of \u03c31 receptors inhibits the pathological activation of astrocytes via modulation of p\u2010p38, which ultimately prevents the development of <jats:styled-content style=\"fixed-case\">MA<\/jats:styled-content> in neuropathic mice.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12893","type":"journal-article","created":{"date-parts":[[2014,8,27]],"date-time":"2014-08-27T04:57:56Z","timestamp":1409115476000},"page":"5881-5897","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["\u03c31 receptors activate astrocytes via p38 <scp>MAPK<\/scp> phosphorylation leading to the development of mechanical allodynia in a mouse model of neuropathic pain"],"prefix":"10.1111","volume":"171","author":[{"given":"J Y","family":"Moon","sequence":"first","affiliation":[{"name":"Department of Veterinary Physiology College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D H","family":"Roh","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial Tissue Regeneration Kyung Hee University School of Dentistry  Seoul 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Veterinary Physiology College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S Y","family":"Kang","sequence":"additional","affiliation":[{"name":"Acupuncture, Moxibustion and Meridian Research Group Medical Research Division, Korea Institute of Oriental Medicine  Daejeon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H J","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Veterinary Physiology College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A J","family":"Beitz","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences College of Veterinary Medicine, University of Minnesota  St Paul MN 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