Cotargeting of peripheral μ-opioid and cannabinoid receptors was found to have a synergistic effect in reducing mechanical allodynia in a mouse model of neuropathic pain in a study presented at the American Pain Society (APS) 2018 meeting, held March 4 to 6 in Anaheim, California.

“Current therapeutic options for the management of neuropathic pain are limited by their undesirable side effect profile that results from their off-target [central nervous system] effects,” pointed out the study authors.

“Our preclinical findings in rodent models of neuropathic pain, using peripherally acting opioids and cannabinoids, suggest that these peripheral targets may provide a novel approach to enhance analgesia while bypassing the off-target central nervous system effects.”

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The investigators of this study sought to determine whether cotreatment with a peripherally restricted opioid (DALDA) and cannabinoid (CB13) would provide synergistic or additive benefit on mechanical hypersensitivity in a mouse model of neuropathic pain.

Compared with vehicle-treated controls, a greater reduction in mechanical hypersensitivity was observed in mice treated with both CB13 and DALDA. Co-administration of the 2 drugs had a synergistic effect in reducing mechanical hypersensitivity.

“Treatment of neuropathic pain is limited by the efficacy and the adverse effects associated with presently available pharmacological therapies,” explained the investigators. “These findings may have significant implications for the development of combination therapies with peripherally acting drugs. Such a strategy needs to be tested in the clinical population suffering from neuropathic pain syndromes,” concluded the study authors.

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Grenald S, Guan Y, and Raja S. Peripheral cannabinoid and mu opioid receptor synergistic inhibition of neuropathic pain. Presented at: American Pain Society (APS) 2018; Anaheim, California; March 4-6, 2018. Abstract 255.