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 2022 DOI: 10.3389/fphar.2022.813562 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Male and female C57BL/6J mice |
| Interventions | 16-Bromo SalA U50 488 morphine |
| Dose | U50,488 10 mg/kg |
| Duration | 23 days |
| Topics | Salvia divinorum |
| Keywords | Chemotherapy-induced neuropathic pain Kappa opioid receptor Paclitaxel Sex differences |
| Key points | 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.
Comparable studies
Other preclinical and animal studies on salvia divinorum, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Effects of the plant-derived hallucinogen salvinorin A on basal dopamine levels in the caudate putamen and in a conditioned place aversion assay in mice: agonist actions at kappa opioid receptors. Mice | 2005 | Experimental study | |
| Potential anxiolytic‐ and antidepressant‐like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents Male Sprague-Dawley rats and male Albino Swiss mice | 2009 | Experimental study | |
| Involvement of kappa-opioid and endocannabinoid system on Salvinorin A-induced reward. Wistar rats | 2008 | Experimental study | |
| Role of kappa-opioid receptors in the effects of salvinorin A and ketamine on attention in rats. Rats | 2010 | Experimental study | |
| The plant-derived hallucinogen, salvinorin A, produces kappa-opioid agonist-like discriminative effects in rhesus monkeys. Rhesus monkeys | 2004 | Experimental study | n = 3 |
Citations in the library
Cited by 2
Cites 7
- Synthesis and κ-opioid receptor activity of furan-substituted salvinorin A analogues. Journal of Medicinal Chemistry December 26, 2014
- Pharmacokinetics of the plant-derived kappa-opioid hallucinogen salvinorin A in nonhuman primates. Synapse December 1, 2005
- A facile method for the preparation of deuterium labeled salvinorin A: synthesis of [2,2,2-2H3]-salvinorin A. Bioorganic & Medicinal Chemistry Letters October 18, 2004
- Potential Drug Abuse Therapeutics Derived from the Hallucinogenic Natural Product Salvinorin A. MedChemComm December 1, 2011
- Neuropathic and inflammatory antinociceptive effects and electrocortical changes produced by Salvia divinorum in rats. Journal of Ethnopharmacology July 12, 2017
and 2 more in the library