Affiliations 

  • 1 Centre for Drug Research, Universiti Sains Malaysia, 11800 Penang, Malaysia
  • 2 Centre for Drug Research, Universiti Sains Malaysia, 11800 Penang, Malaysia; Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia
  • 3 Departments of Psychiatry and Emergency Medicine, Yale School of Medicine, New Haven, CT, United States
  • 4 Centre for Drug Research, Universiti Sains Malaysia, 11800 Penang, Malaysia. Electronic address: zurina_hassan@usm.my
Behav Brain Res, 2023 Feb 15;439:114251.
PMID: 36503042 DOI: 10.1016/j.bbr.2022.114251

Abstract

Mitragynine exerts its analgesic effect mainly via opioid receptors activation. Additionally, the effect may be mediated via mitragynine's anti-inflammatory property and non-opioid receptor pain pathways, namely through the TRPV1 receptor. No studies identify hitherto, hence, the current study aimed to investigate the mitragynine's analgesic effect via the anti-inflammatory property, non-opioid receptor (TRPV1) and the effective dose (ED) to alleviate pain. Male and female Sprague Dawley rats were pre-treated intraperitoneally with either mitragynine (1, 5, 10, 13, 15 or 30 mg/kg), vehicle, or indomethacin (1 mg/kg) 30 min before inducing inflammatory pain using acetic acid. The writhes and pain-related withdrawal behaviour occurrence were counted within a 1-h duration. Percentage of writhes inhibition, pain-related withdrawal behaviour aggregate, ED50 and ED95 were determined. The body temperature was recorded and TRPV1 expression in the rats' brains was measured. Mitragynine (except 1 mg/kg) significantly reduced the number of writhes compared with the vehicle administered group. Mitragynine (30 mg/kg) demonstrated 99.5% inhibition of writhing behaviour and low withdrawal behaviour score compared with vehicle and indomethacin and successfully blocked the hypothermia induced by acetic acid. The overall ED50 and ED95 values of mitragynine were 3.62 and 20.84 mg/kg, respectively. The percentage of writhing inhibition and withdrawal behaviour were similar in both genders. Mitragynine (15 and 30 mg/kg) significantly reduced the TRPV1 expression in the brain of the rats. Mitragynine alleviated pain-like behaviour and showed analgesic effects via anti-inflammatory and non-opioid receptor pathways. The findings also suggest that mitragynine might regulate some physiological functions of the rat.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.