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Cannabinoid receptor 2 (\n                    <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>\n                    2) has emerged as a promising target for treating different neuropathic pain syndromes. In neuropathic pain models, activated microglia expressing\n                    <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>\n                    2 receptors are seen in the spinal cord. Chemokine fractalkine receptor (\n                    <jats:styled-content style=\"fixed-case\">CX<\/jats:styled-content>\n                    3\n                    <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>\n                    1) plays a substantial role in microglial activation and neuroinflammation. We hypothesized that a\n                    <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>\n                    2 agonist could modulate neuroinflammation and neuropathic pain in an ischemia model of\n                    <jats:styled-content style=\"fixed-case\">CRPS<\/jats:styled-content>\n                    by regulating\n                    <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>\n                    2 and\n                    <jats:styled-content style=\"fixed-case\">CX<\/jats:styled-content>\n                    3\n                    <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>\n                    1 signaling. We used chronic post\u2010ischemia pain (\n                    <jats:styled-content style=\"fixed-case\">CPIP<\/jats:styled-content>\n                    ) as a model of\n                    <jats:styled-content style=\"fixed-case\">CRPS<\/jats:styled-content>\n                    \u2010I. Rats in the\n                    <jats:styled-content style=\"fixed-case\">CPIP<\/jats:styled-content>\n                    group exhibited significant hyperemia and edema of the ischemic hindpaw and spontaneous pain behaviors (hindpaw shaking and licking). Intraperitoneal administration of\n                    <jats:styled-content style=\"fixed-case\">MDA<\/jats:styled-content>\n                    7 (a selective\n                    <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>\n                    2 agonist) attenuated mechanical allodynia induced by\n                    <jats:styled-content style=\"fixed-case\">CPIP<\/jats:styled-content>\n                    .\n                    <jats:styled-content style=\"fixed-case\">MDA<\/jats:styled-content>\n                    7 treatment was found to interfere with early events in the\n                    <jats:styled-content style=\"fixed-case\">CRPS<\/jats:styled-content>\n                    \u2010I neuroinflammatory response by suppressing peripheral edema, spinal microglial activation and expression of\n                    <jats:styled-content style=\"fixed-case\">CX<\/jats:styled-content>\n                    3\n                    <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>\n                    1 and\n                    <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>\n                    2 receptors on the microglia in the spinal cord.\n                    <jats:styled-content style=\"fixed-case\">MDA<\/jats:styled-content>\n                    7 also mitigated the loss of intraepidermal nerve fibers induced by\n                    <jats:styled-content style=\"fixed-case\">CPIP<\/jats:styled-content>\n                    . Neuroprotective effects of\n                    <jats:styled-content style=\"fixed-case\">MDA<\/jats:styled-content>\n                    7 were blocked by a\n                    <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>\n                    2 antagonist,\n                    <jats:styled-content style=\"fixed-case\">AM<\/jats:styled-content>\n                    630. Our findings suggest that\n                    <jats:styled-content style=\"fixed-case\">MDA<\/jats:styled-content>\n                    7, a novel\n                    <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>\n                    2 agonist, may offer an innovative therapeutic approach for treating neuropathic symptoms and neuroinflammatory responses induced by\n                    <jats:styled-content style=\"fixed-case\">CRPS<\/jats:styled-content>\n                    \u2010I in the setting of ischemia and reperfusion injury.\n                  <\/jats:p>","DOI":"10.1111\/ejn.13414","type":"journal-article","created":{"date-parts":[[2016,9,26]],"date-time":"2016-09-26T08:52:44Z","timestamp":1474879964000},"page":"3046-3055","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Activation of cannabinoid receptor 2 attenuates mechanical allodynia and neuroinflammatory responses in a chronic 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