Mitragynine, bioactive alkaloid of kratom, reduces chemotherapy-induced neuropathic pain in rats through α-adrenoceptor mechanism.

Drug and Alcohol Dependence
Jeffery D FossScott M Rawls

Abstract

Kratom is a coffee-like plant containing compounds that cause opioid and stimulant effects. The most prevalent bioactive alkaloid of kratom is mitragynine (MG). Opioid effects of MG are apparent (e.g. antinociception and nanomolar affinity for μ, κ and δ opioid receptors), but effects encompassing interactions with additional systems, such as adrenergic and dopaminergic, remain undefined. Given that enhanced adrenergic transmission is a mechanism common to most first-line neuropathic pain medications, we tested the hypothesis that MG reduces chemotherapy-induced neuropathic pain through a mechanism involving α-adrenoceptor activation. Rats were injected once with oxaliplatin (6 mg/kg IP) to induce allodynia and then treated with MG (0, 1, 5, 10 mg/kg IP) for 5-7 days. To investigate receptor mechanisms, a fixed dose of MG (5 mg/kg IP) was injected with yohimbine (5 mg/kg IP, α2-adrenoceptor antagonist), prazosin (5 mg/kg IP, α1-adrenoceptor antagonist), or naltrexone (5 mg/kg IP, opioid antagonist). MG (5, 10 mg/kg) dose-dependently reduced mechanical sensitivity in oxaliplatin-injected rats. Anti-allodynic effects of MG were completely inhibited by yohimbine, and significantly reduced by prazosin and naltrexone. MG produced mo...Continue Reading

Citations

Jun 20, 2021·Physiology & Behavior·Sarah UddinScott M Rawls
Jul 27, 2021·Human Psychopharmacology·Elisabeth PreveteJohannes Gerardus Ramaekers
Sep 18, 2021·Der Schmerz·Florian LautenschlagerNorbert Wodarz

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