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Mechanisms underlying P\u2010APS remain largely unknown. We recently reported that rodents receiving paclitaxel develop acute pain and activation of spinal microglial toll like receptor 4 (TLR4) by paclitaxel penetrating into the spinal cord is a critical event in the genesis of P\u2010APS. Our current study dissected cellular and molecular mechanisms underlying the P\u2010APS. We demonstrated that bath\u2010perfusion of paclitaxel, at a concentration similar to that found in the cerebral spinal fluid in animals receiving i.v. paclitaxel (2\u2009mg\/kg), resulted in increased calcium activity in microglia instantly, and in astrocytes with 6\u2009min delay. TLR4 activation in microglia by paclitaxel caused microglia to rapidly release interleukin\u20101\u03b2 (IL\u20101\u03b2) but not tumor necrosis factor \u03b1, IL\u20106, or interferon\u2010\u03b3. IL\u20101\u03b2 release from microglia depended on capthepsin B. IL\u20101\u03b2 acted on astrocytes, leading to elevated calcium activity and suppressed glutamate uptake. IL\u20101\u03b2 also acted on neurons to increase presynaptic glutamate release and postsynaptic AMPA receptor activity in the spinal dorsal horn. Knockout of IL\u20101 receptors prevented the development of acute pain induced by paclitaxel in mice. Our study indicates that IL\u20101\u03b2 is a crucial molecule used by microglia to alter functions in astrocytes and neurons upon activation of TLR4 in the genesis of P\u2010APS, and targeting the signaling pathways regulating the production and function of IL\u20101\u03b2 from microglia is a potential avenue for the development of analgesics for the treatment of P\u2010APS.<\/jats:p>","DOI":"10.1002\/glia.23557","type":"journal-article","created":{"date-parts":[[2018,12,22]],"date-time":"2018-12-22T00:58:48Z","timestamp":1545440328000},"page":"482-497","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Interleukin\u20101beta released by microglia initiates the enhanced glutamatergic activity in the spinal dorsal horn during paclitaxel\u2010associated acute pain syndrome"],"prefix":"10.1002","volume":"67","author":[{"given":"Xisheng","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical and Biomedical Sciences The University of Georgia College of Pharmacy  Athens Georgia"},{"name":"Department of Cardiovascular Medicine Wuhan Third Hospital  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology Wuhan Third Hospital  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan W.","family":"Maixner","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Biomedical Sciences The University of Georgia College of Pharmacy  Athens Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchi","family":"Yadav","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Biomedical Sciences The University of Georgia College of Pharmacy  Athens Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Biomedical Sciences The University of Georgia College of Pharmacy  Athens Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mourad Wagdy","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Biomedical Sciences The University of Georgia College of Pharmacy  Athens Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelley B.","family":"Hooks","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Biomedical Sciences The University of Georgia College of Pharmacy  Athens Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2062-2782","authenticated-orcid":false,"given":"Han\u2010Rong","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Biomedical Sciences The University of Georgia College of Pharmacy  Athens Georgia"},{"name":"Department of Biomedical Sciences Mercer University School of Medicine  Macon Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2014.06.007"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3957-09.2010"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047988"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80420-1"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2012.08.088"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2012.01.018"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2010.10.030"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2012.02.008"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20117"},{"key":"e_1_2_9_11_1","first-page":"151","article-title":"Clinical and experimental findings in humans and animals with chemotherapy\u2010induced peripheral neuropathy","volume":"72","author":"Cata J. 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