A bivalent compound targeting CCR5 and the mu opioid receptor treats inflammatory arthritis pain in mice without inducing pharmacologic tolerance

Abstract

Furthermore, prolonged administration of morphine did not increase the baseline pain threshold, whereas MCC22 did (Figs. 2a and 4). [...]MCC22 is substantially more potent than morphine and also does not cause typical opioid tolerance. Furthermore, because of their addictive and dependent properties, misuse of prescription opioids has massively increased in recent years. [...]there is an intense demand to develop safer alternatives to manage pain in patients with arthritis. [...]the main benefit of the CCR5 antagonist moiety of MCC22 in this system is to improve the analgesic potency of its MOR agonist moiety, likely by engaging MOR-CCR5 heterodimers. MCC22 similarly produced no condition-place preference, a measure of reward-seeking, in a different murine model of pain (our unpublished data). [...]in the setting of arthritis, MCC22 appears to have a similar analgesic and low side-effect profile to NFEPP, but with greater potency.