Delta- and mu-opioid pathways are involved in the analgesic effect of Ocimum basilicum L in mice

J Ethnopharmacol. 2020 Mar 25:250:112471. doi: 10.1016/j.jep.2019.112471. Epub 2019 Dec 16.

Abstract

Ethnopharmacological relevance: Ocimum basilicum L. is a perennial herb that has been used in traditional Asian Indian medicine for thousands of years as a natural anti-inflammatory, antibiotic, diuretic, and analgesic.

Aim of the study: The present study was conducted to investigate the analgesic effects of basil essential oil (BEO) in inflammatory pain models and identify underlying mechanisms. We further investigated whether BEO affects physiological pain and motor coordination.

Materials and methods: The analgesic effects of BEO were assessed in various mouse experimental pain models using formalin, acetic acid, heat, and carrageenan as stimuli. BEO was administered by intraperitoneal injection or inhalation. The involvement of various pathways in the analgesic effect of BEO was assessed by pretreating mice with selective pharmacological inhibitors, administered intraperitoneally. Opioid pathways were tested using the κ-opioid antagonist 5'-guanidinonaltrindole (GNTI; 0.3 mg/kg), δ-opioid antagonist naltrindole (NTD; 5 mg/kg) and μ-opioid antagonist naloxone (NAL; 8 mg/kg); nitric oxide (NO) pathways were tested using the NO synthase inhibitor N-nitro l-arginine methyl ester (L-NAME; 37.5 mg/kg) and NO precursor L-arginine (L-Arg; 600 mg/kg); and KATP channel pathways were tested using the ATP-sensitive K+ channel blocker, glibenclamide-hippuric acid (GHA, 2 mg/kg). Potential effects of BEO on motor coordination were assessed using a rotarod test.

Results: BEO exerted analgesic effects in all pain models. Notably, pretreatment with naltrindole, naloxone, or L-arginine significantly reduced the analgesic effects of BEO in the formalin test. BEO increased mean withdrawal latencies in a thermal plantar test at a high dose, but not at lower doses. BEO had no effect on motor coordination.

Conclusions: Our findings indicate that the analgesic effects of BEO are primarily mediated by delta- and mu-opioid pathways and further suggest that BEO has potential for development as an analgesic agent for the relief of inflammatory pain.

Keywords: Acetic-acid test; Formalin test; Ocimum basilicum L.; Opioid pathway; Pain.

MeSH terms

  • Analgesics / administration & dosage
  • Analgesics / isolation & purification
  • Analgesics / pharmacology*
  • Animals
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Ocimum basilicum / chemistry*
  • Oils, Volatile / administration & dosage
  • Oils, Volatile / isolation & purification
  • Oils, Volatile / pharmacology*
  • Pain / drug therapy*
  • Pain / physiopathology
  • Receptors, Opioid, delta / drug effects
  • Receptors, Opioid, delta / metabolism
  • Receptors, Opioid, mu / drug effects
  • Receptors, Opioid, mu / metabolism

Substances

  • Analgesics
  • Oils, Volatile
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu