TRPV1 antagonistic analgesic effect: a randomized study of AZD1386 in pain after third molar extraction

Pain. 2013 Jun;154(6):808-12. doi: 10.1016/j.pain.2013.02.004. Epub 2013 Feb 19.


The effects of a TRPV1 antagonist (AZD1386) were investigated in patients with acute pain. After removal of a mandibular third molar and at request of analgesia 103 patients randomly received 95 mg AZD1386 (n = 40), placebo (n = 40) or 500 mg naproxen (n = 23) in a double-blind manner. Plasma samples were drawn, and pain intensity and body temperature were measured during 8 h after drug administration. The pain intensity difference from drug intake was calculated as a percentage (PID%) and as a weighted sum over the 8 h (SPID%0-8 h). The time to first perceptible and first meaningful pain relief was recorded. SPID%(0-8) h showed no significant difference between AZD1386 and placebo (P = .132) but between naproxen and placebo (P = .038). AZD1386 had a rapid short-lasting analgesia and compared to placebo, PID% was significantly higher (P ≤ .026) at 0.25, 0.50, 0.75 and 1.00 h after drug administration. Correspondingly, for naproxen significantly higher PID% (P ≤ .021) was seen at 2.5, 3, 4, 5, 6, 7 and 8 h. The frequency of patients obtaining perceptible and meaningful pain relief was about 85% and 48% after AZD1386 and about 53% and 25% after placebo. The occurrence of perceptible and meaningful pain relief was significantly faster (P = .002 and P = .031) for AZD1386 compared to placebo. Adverse events were similar to placebo with the exception of 2 patients reporting chills. The highest individual body temperature after AZD1386 was 38.1°C, recorded in 2 patients. In summary, AZD1386 was well tolerated with a rapid analgesia that was short lasting despite sustained plasma concentration.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Analgesics / therapeutic use*
  • Benzimidazoles / therapeutic use*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Molar, Third / surgery*
  • Naproxen / therapeutic use
  • Pain Measurement
  • Pain, Postoperative / drug therapy*
  • TRPV Cation Channels / antagonists & inhibitors*
  • Tooth Extraction / adverse effects*
  • Treatment Outcome


  • AZD1386
  • Analgesics
  • Benzimidazoles
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Naproxen