TRPV1 is a novel target for omega-3 polyunsaturated fatty acids

J Physiol. 2007 Jan 15;578(Pt 2):397-411. doi: 10.1113/jphysiol.2006.121988. Epub 2006 Oct 12.


Omega-3 (n-3) fatty acids are essential for proper neuronal function, and they possess prominent analgesic properties, yet their underlying signalling mechanisms are unclear. Here we show that n-3 fatty acids interact directly with TRPV1, an ion channel expressed in nociceptive neurones and brain. These fatty acids activate TRPV1 in a phosphorylation-dependent manner, enhance responses to extracellular protons, and displace binding of the ultrapotent TRPV1 ligand [3H]resiniferatoxin. In contrast to their agonistic properties, n-3 fatty acids competitively inhibit the responses of vanilloid agonists. These actions occur in mammalian cells in the physiological concentration range of 1-10 mum. Significantly, docosahexaenoic acid exhibits the greatest efficacy as an agonist, whereas eicosapentaenoic acid and linolenic acid are markedly more effective inhibitors. Similarly, eicosapentaenoic acid but not docosahexaenoic acid profoundly reduces capsaicin-evoked pain-related behaviour in mice. These effects are independent of alterations in membrane elasticity because the micelle-forming detergent Triton X-100 only minimally affects TRPV1 properties. Thus, n-3 fatty acids differentially regulate TRPV1 and this form of signalling may contribute to their biological effects. Further, these results suggest that dietary supplementation with selective n-3 fatty acids would be most beneficial for the treatment of pain.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Binding, Competitive / drug effects
  • Calcium / metabolism
  • Capsaicin / analogs & derivatives
  • Capsaicin / pharmacology
  • Capsaicin / toxicity
  • Cell Line
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Diterpenes / metabolism
  • Fatty Acids, Omega-3 / pharmacology*
  • Fatty Acids, Omega-6 / pharmacology
  • Female
  • Humans
  • Hydrogen-Ion Concentration
  • Linoleic Acid / pharmacology
  • Male
  • Membrane Fluidity / drug effects
  • Membrane Potentials / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Oocytes / physiology
  • Pain / chemically induced
  • Pain / prevention & control
  • RNA, Complementary / administration & dosage
  • RNA, Complementary / genetics
  • Rats
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / physiology*
  • Xenopus laevis


  • Diterpenes
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • RNA, Complementary
  • TRPV Cation Channels
  • Trpv1 protein, rat
  • Linoleic Acid
  • resiniferatoxin
  • capsazepine
  • Capsaicin
  • Calcium