Antinociceptive effect and the mechanism of bee venom acupuncture (Apipuncture) on inflammatory pain in the rat model of collagen-induced arthritis: Mediation by alpha2-Adrenoceptors

Brain Res. 2006 Feb 16:1073-1074:305-10. doi: 10.1016/j.brainres.2005.12.086. Epub 2006 Feb 2.


The antinociceptive effect and the mechanism of bee venom acupuncture (BVA) on inflammatory pain, especially in the rat model of collagen-induced arthritis (CIA), have not yet been fully studied. This study was designed to investigate the antinociceptive effect and its mu-opioid and alpha2-adrenergic mechanism of BVA in the CIA rat model. To induce CIA, male Sprague-Dawley rats were immunized with bovine type II collagen emulsified in Freund's incomplete adjuvant followed by a booster injection 14 days later. The antinociceptive effect was evaluated by tail flick latency (TFL). After induction of arthritis, the inflammatory pain threshold decreased as time passed, and there was no big change of the pain threshold after 3 weeks. Three weeks after the first immunization, BVA (0.25 mg/kg) injected into the Zusanli acupoint (ST36) showed the antinociceptive effect. Furthermore, the antinociceptive effect of BVA was blocked by yohimbine (alpha2-adrenergic receptor antagonist, 2 mg/kg, i.p) pretreatment, but not by naloxone (mu-opioid receptor antagonist, 2 mg/kg, i.p.) pretreatment. These results suggest that BVA can relieve inflammatory pain in CIA and the antinociceptive effect of BVA can be mediated by alpha2-adrenergic receptor.

Publication types

  • Comparative Study

MeSH terms

  • Acupuncture Points*
  • Adrenergic alpha-Antagonists / administration & dosage
  • Animals
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / complications
  • Arthritis, Experimental / drug therapy*
  • Bee Venoms / administration & dosage*
  • Behavior, Animal
  • Collagen / toxicity
  • Disease Models, Animal
  • Drug Administration Routes
  • Drug Interactions
  • Male
  • Naloxone / administration & dosage
  • Narcotic Antagonists / administration & dosage
  • Pain / etiology
  • Pain Management*
  • Pain Measurement / methods
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Receptors, Adrenergic, alpha-2 / physiology*
  • Statistics, Nonparametric
  • Yohimbine / administration & dosage


  • Adrenergic alpha-Antagonists
  • Bee Venoms
  • Narcotic Antagonists
  • Receptors, Adrenergic, alpha-2
  • Yohimbine
  • Naloxone
  • Collagen