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Synergistic attenuation of chronic pain using mu opioid and cannabinoid receptor 2 agonists
- Source :
- Neuropharmacology. 116
- Publication Year :
- 2016
-
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.
- Subjects :
- 0301 basic medicine
Agonist
Male
Indoles
medicine.drug_class
Dopamine
Analgesic
Receptors, Opioid, mu
Pharmacology
Article
Rats, Sprague-Dawley
Receptor, Cannabinoid, CB2
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Reward
medicine
Cannabinoid receptor type 2
Animals
Cannabinoid Receptor Agonists
Mice, Inbred ICR
Dose-Response Relationship, Drug
Morphine
Chemistry
Chronic pain
Drug Synergism
Analgesics, Non-Narcotic
medicine.disease
Corpus Striatum
Acetaminophen
Analgesics, Opioid
Disease Models, Animal
030104 developmental biology
Neuropathic pain
lipids (amino acids, peptides, and proteins)
μ-opioid receptor
Chronic Pain
Constipation
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 18737064
- Volume :
- 116
- Database :
- OpenAIRE
- Journal :
- Neuropharmacology
- Accession number :
- edsair.doi.dedup.....1e7363b5df365c17cf224d6ba5732ae8