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We demonstrate A\n                    <jats:sub>3<\/jats:sub>\n                    adenosine receptor (A\n                    <jats:sub>3<\/jats:sub>\n                    AR) agonism as a new target\u2010based therapeutic strategy. The development of mechanoallodynia in a well\u2010characterized mouse model of neuropathic pain following chronic constriction injury of the sciatic nerve was rapidly and dose\u2010depend\u2010ently reversed by the A\n                    <jats:sub>3<\/jats:sub>\n                    AR agonists: IB\u2010MECA, its 2\u2010chlorinated analog (Cl\u2010IB\u2010MECA), and the structurally distinct MRS1898. These effects were naloxone insensitive and thus are not opioid receptor mediated. IB\u2010MECA was \u22651.6\u2010fold more efficacious than morphine and &gt;5\u2010fold more potent. In addition, IB\u2010MECA was equally efficacious as gabapentin (Neurontin) or amitriptyline, but respectively &gt;350\u2010 and &gt;75\u2010fold more potent. Besides its potent standalone ability to reverse established mechanoallodynia, IB\u2010MECA significantly increased the antiallodynic effects of all 3 analgesics. Moreover, neuropathic pain development in rats caused by widely used chemotherapeutics in the taxane (paclitaxel), platinum\u2010complex (oxaliplatin), and proteasome\u2010inhibitor (bortezomib) classes was blocked by IB\u2010MECA without antagonizing their antitumor effect. A\n                    <jats:sub>3<\/jats:sub>\n                    AR agonist effects were blocked with A\n                    <jats:sub>3<\/jats:sub>\n                    AR antagonist MRS1523, but not with A\n                    <jats:sub>1<\/jats:sub>\n                    AR (DPCPX) or A\n                    <jats:sub>2A<\/jats:sub>\n                    AR (SCH\u2010442416) antagonists. Our findings provide the scientific rationale and pharmacological basis for therapeutic development of A\n                    <jats:sub>3<\/jats:sub>\n                    AR agonists for chronic pain.\u2014Chen, Z., Janes, K., Chen, C., Doyle, T., Bryant, L., Tosh, D.K., Jacobson, K.A., Salvemini, D. Controlling murine and rat chronic pain through A\n                    <jats:sub>3<\/jats:sub>\n                    adenosine receptor activation.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    26, 1855\u20101865 (2012).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.11-201541","type":"journal-article","created":{"date-parts":[[2012,2,17]],"date-time":"2012-02-17T21:29:31Z","timestamp":1329514171000},"page":"1855-1865","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":100,"title":["Controlling murine and rat chronic pain through A\n                    <sub>3<\/sub>\n                    adenosine receptor activation"],"prefix":"10.1096","volume":"26","author":[{"given":"Zhoumou","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmacological and Physiological Science St. Louis University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kali","family":"Janes","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Physiological Science St. Louis University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Physiological Science St. Louis University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Doyle","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Physiological Science St. Louis University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leesa","family":"Bryant","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Physiological Science St. Louis University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilip K.","family":"Tosh","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth A.","family":"Jacobson","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Salvemini","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Physiological Science St. Louis University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,2,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2005.11.008"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/SPC.0b013e328342f9cc"},{"key":"e_1_2_7_4_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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