Arizona Health Sciences

Synergistic attenuation of chronic pain using mu opioid and cannabinoid receptor 2 agonists.

TitleSynergistic attenuation of chronic pain using mu opioid and cannabinoid receptor 2 agonists.
Publication TypeJournal Article
Year of Publication2017
AuthorsGrenald SA, Young MA, Wang Y, Ossipov MH, Ibrahim MM, Largent-Milnes TM, Vanderah TW
JournalNeuropharmacology
Volume116
Pagination59-70
Date Published2017 Apr
ISSN1873-7064
Abstract

The misuse of prescription opiates is on the rise with combination therapies (e.g. acetaminophen or NSAIDs) resulting in severe liver and kidney damage. In recent years, cannabinoid receptors have been identified as potential modulators of pain and rewarding behaviors associated with cocaine, nicotine and ethanol in preclinical models. Yet, few studies have identified whether mu opioid agonists and CB2 agonists act synergistically to inhibit chronic pain while reducing unwanted side effects including reward liability. We determined if analgesic synergy exists between the mu-opioid agonist morphine and the selective CB2 agonist, JWH015, in rodent models of acute and chronic inflammatory, post-operative, and neuropathic pain using isobolographic analysis. We also investigated if the MOR-CB2 agonist combination decreased morphine-induced conditioned place preference (CPP) and slowing of gastrointestinal transit. Co-administration of morphine with JWH015 synergistically inhibited preclinical inflammatory, post-operative and neuropathic-pain in a dose- and time-dependent manner; no synergy was observed for nociceptive pain. Opioid-induced side effects of impaired gastrointestinal transit and CPP were significantly reduced in the presence of JWH015. Here we show that MOR + CB2 agonism results in a significant synergistic inhibition of preclinical pain while significantly reducing opioid-induced unwanted side effects. The opioid sparing effect of CB2 receptor agonism strongly supports the advancement of a MOR-CB2 agonist combinatorial pain therapy for clinical trials.

DOI10.1016/j.neuropharm.2016.12.008
Alternate JournalNeuropharmacology
PubMed ID28007501
PubMed Central IDPMC5385155
Grant ListR01 CA142115 / CA / NCI NIH HHS / United States
Faculty Member Reference: 
Mohab M. Ibrahim, PhD, MD
Tally Largent-Milnes, Ph.D.
Todd Vanderah, Ph.D.