{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:26:40Z","timestamp":1787236000971,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2016,7,13]],"date-time":"2016-07-13T00:00:00Z","timestamp":1468368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Clinical studies have reported that pan\u2010cannabinoid receptor agonists may have efficacy in neuropathic pain states and that this might be enhanced by co\u2010administration with opioids. While cannabinoid\u2013opioid analgesic synergy has been demonstrated in animal models of acute pain, it has not been examined in neuropathic pain models. We examined the effect of combination treatment with cannabinoid and opioid receptor agonists on allodynia and side effects in a nerve injury\u2010induced neuropathic pain model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>C57BL\/6 mice were subjected to chronic constriction injury (CCI) of the sciatic nerve. The effects of systemic administration of morphine and the pan\u2010cannabinoid receptor agonist, WIN55212, on allodynia and side effects were examined at 7\u201310\u00a0days post\u2010CCI surgery. Isobolographic analysis was used to determine whether the effects of the combination were synergistic.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>The opioid agonist morphine reduced CCI\u2010induced mechanical and cold allodynia and produced motor incoordination, in a dose\u2010dependent manner. WIN55212 reduced CCI\u2010induced allodynia and produced motor incoordination, catalepsy and sedation, in a dose\u2010dependent manner, as we have observed previously. When administered together, WIN55212 and morphine reduced allodynia in a synergistic manner but had only an additive effect on motor incoordination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>These findings indicate that administration of a combination of a non\u2010selective opioid and cannabinoid receptor agonist synergistically reduces nerve injury\u2010induced allodynia, while producing side effects in an additive manner. This suggests that this combination treatment has an improved anti\u2010allodynic potency and therapeutic index in a neuropathic pain model.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.13534","type":"journal-article","created":{"date-parts":[[2016,6,9]],"date-time":"2016-06-09T12:01:22Z","timestamp":1465473682000},"page":"2521-2531","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Opioid and cannabinoid synergy in a mouse neuropathic pain model"],"prefix":"10.1111","volume":"173","author":[{"given":"Nicholas P","family":"Kazantzis","sequence":"first","affiliation":[{"name":"Pain Management Research Institute, Kolling Institute of Medical Research, Northern Clinical School University of Sydney at Royal North Shore Hospital  St Leonards NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherelle L","family":"Casey","sequence":"additional","affiliation":[{"name":"Pain Management Research Institute, Kolling Institute of Medical Research, Northern Clinical School University of Sydney at Royal North Shore Hospital  St Leonards NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick W","family":"Seow","sequence":"additional","affiliation":[{"name":"Pain Management Research Institute, Kolling Institute of Medical Research, Northern Clinical School University of Sydney at Royal North Shore Hospital  St Leonards NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa A","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Pain Management Research Institute, Kolling Institute of Medical Research, Northern Clinical School University of Sydney at Royal North Shore Hospital  St Leonards NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher W","family":"Vaughan","sequence":"additional","affiliation":[{"name":"Pain Management Research Institute, 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