Evaluation of the effects of a metabotropic glutamate receptor 5-antagonist on electrically induced pain and central sensitization in healthy human volunteers

Eur J Pain. 2013 Nov;17(10):1465-71. doi: 10.1002/j.1532-2149.2013.00327.x. Epub 2013 May 6.


Background: This study aimed to investigate the effect of a single dose of the mGluR5-antagonist AZD9272 on electrically induced pain, central sensitization and axon reflex flare.

Methods: This was a randomized, double-blind, placebo-controlled crossover study. Twenty-five healthy male volunteers received a single oral dose of AZD9272 or placebo on two occasions separated by 10-20 days. Electrical stimulation with a constant current for 100 min delivered through intracutaneous electrodes inserted on the forearm was used to induce a stable level of pain (6 of 10 on a 0-10 numerical rating scale; NRS). Pain intensity was assessed every 10 min during stimulation. The area of punctate hyperalgesia, area of dynamic mechanical allodynia, and area and intensity of flare reaction were measured every 20 min during stimulation. The stimulation procedure, current intensity and measurements were identical at both treatment visits. The AUC0-100 min (area under curve, 100 min stimulation) was calculated for each variable. The AUC0-100 min for pain NRS and hyperalgesia area were defined as primary variables. Linear mixed effects models were used for the statistical analysis.

Results: Twenty-one subjects completed the study per protocol. No significant differences were found between AZD9272 and placebo regarding any of the AUC0-100 min variables for pain NRS, hyperalgesia area, allodynia area, flare area or flare intensity. The plasma levels of AZD9272 were maximal during the pain measurements and corresponded to >50% brain mGluR5 receptor occupancy.

Conclusion: Single doses of the centrally acting mGluR5-antagonist AZD9272 did not reduce C-fibre evoked pain, central sensitization or flare reaction.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Central Nervous System Sensitization / drug effects*
  • Double-Blind Method
  • Evoked Potentials
  • Healthy Volunteers
  • Humans
  • Hyperalgesia / drug therapy*
  • Oxadiazoles / therapeutic use*
  • Pain / drug therapy*
  • Pain Measurement / drug effects
  • Pain Threshold / drug effects
  • Pyridines / therapeutic use*
  • Receptor, Metabotropic Glutamate 5 / antagonists & inhibitors*
  • Skin / drug effects
  • Young Adult


  • AZD9272
  • Oxadiazoles
  • Pyridines
  • Receptor, Metabotropic Glutamate 5