Opioid and cannabinoid synergy in a mouse neuropathic pain model

Kazantzis, Nicholas P; Casey, Sherelle L; Seow, Patrick W; Mitchell, Vanessa A; Vaughan, Christopher W

doi:10.1111/bph.13534

Cited by 72Pain Mechanisms and TreatmentsCannabis and Cannabinoid ResearchPain Management and Opioid Use

Opioid and cannabinoid synergy in a mouse neuropathic pain model

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Kazantzis, Nicholas P, Casey, Sherelle L, Seow, Patrick W, Mitchell, Vanessa A, Vaughan, Christopher W·2016·British Journal of Pharmacology

DOI 10.1111/bph.13534PMC PMC4959956

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Abstract

Background and Purpose: Clinical studies have reported that pan‐cannabinoid receptor agonists may have efficacy in neuropathic pain states and that this might be enhanced by co‐administration with opioids. While cannabinoid–opioid 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‐induced neuropathic pain model. Experimental Approach: C57BL/6 mice were subjected to chronic constriction injury (CCI) of the sciatic nerve. The effects of systemic administration of morphine and the pan‐cannabinoid receptor agonist, WIN55212, on allodynia and side effects were examined at 7–10 days post‐CCI surgery. Isobolographic analysis was used to determine whether the effects of the combination were synergistic. Key Results: The opioid agonist morphine reduced CCI‐induced mechanical and cold allodynia and produced motor incoordination, in a dose‐dependent manner. WIN55212 reduced CCI‐induced allodynia and produced motor incoordination, catalepsy and sedation, in a dose‐dependent 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. Conclusions and Implications: These findings indicate that administration of a combination of a non‐selective opioid and cannabinoid receptor agonist synergistically reduces nerve injury‐induced allodynia, while producing side effects in an additive manner. This suggests that this combination treatment has an improved anti‐allodynic potency and therapeutic index in a neuropathic pain model.

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Combination of morphine and the cannabinoid receptor agonist WIN55,212 produces synergistic anti-mechanical and cold allodynia in the mouse CCI model of neuropathic pain.
“Combination of morphine and the cannabinoid receptor agonist WIN55,212 produces synergistic anti-mechanical and cold allodynia in the mouse CCI model of neuropathic pain but acts in an additive manner in the impairment of motor coordination as assessed with the rotarod assay (Kazantzis et al, 2016).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Kazantzis et al, 2016

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Authors: Kazantzis, N. P., Casey, S. L., Seow, P. W., Mitchell, V. A., & Vaughan, C. W.
Affiliations: The University of Sydney (AU)
Corresponding author: Vaughan, Christopher W
ORCID: Casey, Sherelle L
Vaughan, Christopher W
Venue: British Journal of Pharmacology
Publisher: Wiley
Published: 2016-07-13
Volume: 173
Issue: 16
Pages: 2521-2531
ISSN: 0007-1188 (ISSN-L)
1476-5381
DOI: 10.1111/bph.13534
PMC: PMC4959956
OpenAlex: W2417541532
Cited by: 71
References: 47
Citations by year: 2026: 1 · 2025: 1 · 2024: 7 · 2023: 10 · 2022: 10 · 2021: 9 · 2020: 8 · 2019: 7 · 2018: 8 · 2017: 9 · 2013: 1
FWCI: 6.43
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: British Journal of Pharmacology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
Keywords: neuropathic pain, cannabinoid receptor agonists, morphine, allodynia, chronic constriction injury, sciatic nerve injury, isobolographic analysis, motor incoordination, sedation, catalepsy, combination analgesia
MeSH terms: Analgesics, Opioid, Animals, Cannabinoids, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Synergism, Male, Mice, Inbred C57BL, Morphine, Neuralgia, Structure-Activity Relationship, Mice

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Opioid and cannabinoid synergy in a mouse neuropathic pain model

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