Differential roles of peripheral metabotropic glutamate receptors in bee venom-induced nociception and inflammation in conscious rats

J Pain. 2010 Apr;11(4):321-9. doi: 10.1016/j.jpain.2009.07.013. Epub 2009 Oct 22.


Intraplantar injection of bee venom (BV) produces persistent spontaneous nociception (PSN), hyperalgesia, and inflammatory swelling of the injected paw. The present study was designed to determine the roles of peripheral metabotropic glutamate receptors (mGluRs) in BV-induced nociception and inflammation. We determined the effects of the group I mGluR antagonist AIDA, the group II mGluR agonist ADPC, and the group III mGluR agonist L-AP4 on BV-induced PSN, mechanical hyperalgesia, and inflammatory swelling. Pretreatment with intraplantar injections of AIDA, ADPC or L-AP4 at different doses significantly inhibited BV-induced PSN over the 1-hour observational period. The inhibitory effects of ADPC and L-AP4 were completely abolished by pretreatment with the group II mGluR antagonist LY341495 and the group III mGluR antagonist MSOP, respectively. Pretreatment with ADPC prevented the BV-induced decrease in paw-withdrawal mechanical threshold (PWMT) in a dose-dependent manner, while pretreatment with AIDA or L-AP4 had no effect. The antihyperalgesic effect of ADPC was completely abolished by pretreatment with LY341495. Pretreatment with AIDA, ADPC or L-AP4 at different doses had no effect on the BV-induced increase in the paw volume (PV), a measurement of inflammatory swelling. All contralateral drug treatments at the highest doses had no effect on BV-induced PSN, decreases in PWMT or increases in PV, eliminating the possibility of drug-induced systemic effects. These data suggest that the activation of mGluRs in the periphery may play a differential role in BV-induced nociception and inflammation.

Perspective: The present study demonstrated that the intraplantar injection of antagonists or agonists of different mGluRs produced differential effects on bee venom-induced persistent spontaneous nociception and mechanical hyperalgesia. However, no effects on inflammation were observed, suggesting that mGluRs in the periphery have differential roles. Thus, therapies specifically targeting metabotropic glutamate receptors may improve the treatment of patients with persistent spontaneous nociception and hyperalgesia.

MeSH terms

  • Animals
  • Bee Venoms / pharmacology*
  • Consciousness
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Drug Synergism
  • Drug Therapy, Combination
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Foot / innervation
  • Foot / physiopathology
  • Glutamic Acid / metabolism
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy
  • Hyperalgesia / physiopathology*
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / physiopathology*
  • Male
  • Nociceptors / drug effects
  • Nociceptors / metabolism*
  • Pain Measurement
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / drug effects
  • Receptors, Metabotropic Glutamate / metabolism*
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / metabolism*
  • Treatment Outcome


  • Bee Venoms
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Receptors, Metabotropic Glutamate
  • Glutamic Acid