Therapeutic potential of vanilloid receptor TRPV1 agonists and antagonists as analgesics: Recent advances and setbacks

Brain Res Rev. 2009 Apr;60(1):267-77. doi: 10.1016/j.brainresrev.2008.12.006. Epub 2008 Dec 25.


The vanilloid receptor TRPV1 is a homotetrameric, non-selective cation channel abundantly expressed in the nociceptors (c-fibers). TRPV1 is considered as a highly validated pain target because, i) its agonists such as capsaicin cause desensitization of TRPV1 channels that relieves pain behaviors in preclinical species, and ii) its antagonists relieve pain behaviors in rodent models of inflammation, osteoarthritis, and cancer. Hence, both agonists and antagonists of TRPV1 are being evaluated as potential analgesics in clinical trials. Clinical trial results of TRPV1 agonists such as resiniferatoxin in interstitial cystitis, NGX 4010 in post-herpetic neuralgia, and 4975 (Adlea) in osteoarthritis, bunionectomy, and Morton's neuroma have been reported. Similarly, clinical trial results of TRPV1 antagonists such as SB-705498 and AMG 517 have also been published recently. Overall, some molecules (e.g., capsaicin) demonstrated potential analgesia in certain conditions (postsurgical pain, postherpetic neuralgia, pain in diabetic neuropathy, osteoarthritis, bunionectomy, and Morton's neuroma), whereas others fell out of the clinic due to on-target liabilities or failed to demonstrate efficacy. This review summarizes recent advances and setbacks of TRPV1 agonists and antagonists in the clinic and predicts future directions.

Publication types

  • Review

MeSH terms

  • Analgesics / chemistry
  • Analgesics / pharmacology*
  • Animals
  • Capsaicin / pharmacology
  • Clinical Trials as Topic / statistics & numerical data
  • Drug Evaluation, Preclinical / methods
  • Humans
  • Nervous System / drug effects*
  • Nervous System / metabolism
  • Nervous System / physiopathology
  • Neuropharmacology / methods
  • Neuropharmacology / trends
  • Nociceptors / drug effects*
  • Nociceptors / metabolism
  • Pain / drug therapy*
  • Pain / metabolism
  • Pain / physiopathology
  • TRPV Cation Channels / agonists*
  • TRPV Cation Channels / antagonists & inhibitors*
  • TRPV Cation Channels / metabolism


  • Analgesics
  • TRPV Cation Channels
  • Capsaicin