Vanilloid receptors: new insights enhance potential as a therapeutic target

Pain. 1996 Dec;68(2-3):195-208. doi: 10.1016/s0304-3959(96)03202-2.


Compounds related to capsaicin and its ultrapotent analog, resiniferatoxin (RTX), collectively referred to as vanilloids, interact at a specific membrane recognition site (vanilloid receptor), expressed almost exclusively by primary sensory neurons involved in nociception and neurogenic inflammation. Desensitization to vanilloids is a promising therapeutic approach to mitigate neuropathic pain and pathological conditions (e.g. vasomotor rhinitis) in which neuropeptides released from primary sensory neurons play a major role. Capsaicin-containing preparations are already commercially available for these purposes. The use of capsaicin, however, is severely limited by its irritancy, and the synthesis of novel vanilloids with an improved pungency/desensitization ratio is an on-going objective. This review highlights the emerging evidence that the vanilloid receptor is not a single receptor but a family of receptors, and that these receptors recognize not simply RTX and capsaicin structural analogs but are broader in their ligand-binding selectivity. We further focus on ligand-induced messenger plasticity, a recently discovered mechanism underlying the analgesic actions of vanilloids. Lastly, we give a brief overview of the current clinical uses of vanilloids and their future therapeutic potential. The possibility is raised that vanilloid receptor subtype-specific drugs may be synthesized, devoid of the undesirable side-effects of capsaicin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Capsaicin* / therapeutic use*
  • Diterpenes / therapeutic use*
  • Down-Regulation
  • Humans
  • Rats
  • Receptors, Cell Surface / drug effects
  • Receptors, Drug / drug effects*
  • Structure-Activity Relationship
  • Up-Regulation


  • Diterpenes
  • Phax protein, rat
  • Receptors, Cell Surface
  • Receptors, Drug
  • resiniferatoxin
  • Capsaicin