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.