Sex Differences in Kappa Opioid Receptor Agonist Mediated Attenuation of Chemotherapy-Induced Neuropathic Pain in Mice.
Kelly F Paton, Dan Luo, Anne C La Flamme, Thomas E Prisinzano, Bronwyn M Kivell
Frontiers in pharmacology January 1, 2022 DOI: 10.3389/fphar.2022.813562 via PubMed
Summary
AI-generated from the abstractKappa opioid receptor (KOR) agonists, including analogues of Salvinorin A, reduced pain in a mouse model of chemotherapy-induced neuropathic pain. 16-Ethynyl SalA was more potent than morphine at reducing mechanical allodynia, and SalA, 16-Ethynyl SalA, and EOM SalB were more potent at reducing cold allodynia. Sex differences appeared in mechanical allodynia testing: U50,488 was more potent in males, SalA more potent in females, but no sex differences occurred in cold allodynia. Chronic U50,488 (10 mg/kg) restored mechanical and cold pain responses to healthy levels over 23 days. KOR agonists may be developed to treat this condition.
Study at a glance
| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Male and female C57BL/6J mice |
| Interventions | 16-Ethynyl SalA 16-Bromo SalA ethyoxymethyl ether (EOM) SalB U50 488 morphine |
| Dose | 10 mg/kg |
| Duration | 23 days |
| Topics | Salvia divinorum |
| Keywords | Chemotherapy-induced neuropathic pain Kappa opioid receptor Paclitaxel Sex differences |
| Key finding | KOR agonists, particularly 16-Ethynyl SalA and U50,488, effectively reduced mechanical and cold allodynia in a mouse model of paclitaxel-induced neuropathic pain, with some sex differences. |
Abstract
Chemotherapy-induced neuropathic pain is a common side effect for cancer patients which has limited effective treatment options. Kappa opioid receptor (KOR) agonists are a promising alternative to currently available opioid drugs due to their low abuse potential. In the current study, we have investigated the effects of Salvinorin A (SalA) analogues, 16-Ethynyl SalA, 16-Bromo SalA and ethyoxymethyl ether (EOM) SalB, and in a preclinical model of paclitaxel-induced neuropathic pain in male and female C57BL/6J mice. Using an acute dose-response procedure, we showed that compared to morphine, 16-Ethynyl SalA was more potent at reducing mechanical allodynia; and SalA, 16-Ethynyl SalA, and EOM SalB were more potent at reducing cold allodynia. In the mechanical allodynia testing, U50,488 was more potent in males and SalA was more potent in females. There were no sex differences in the acute cold allodynia testing. In the chronic administration model, treatment with U50,488 (10 mg/kg) reduced the mechanical and cold allodynia responses to healthy levels over 23 days of treatment. Overall, we have shown that KOR agonists are effective in a model of chemotherapy-induced neuropathic pain, indicating that KOR agonists could be further developed to treat this debilitating condition.