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Fats Deliver a Painful Message

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Sci. Signal.  10 Nov 2009:
Vol. 2, Issue 96, pp. ec357
DOI: 10.1126/scisignal.296ec357

Inflammation can make normally nonpainful stimuli cause pain (a phenomenon known as allodynia), and transient receptor potential vanilloid 1 (TRPV1) has been implicated in producing allodynia. TRPV1 is activated by noxious heat, protons (acid conditions), and endogenous ligands such as eicosanoids and endocannabinoids (see Oh and Wood). Patwardhan et al. show that depolarized isolated rat spinal cord released molecules that stimulated cultured trigeminal sensory neurons, many of which have TRPV1 channels. The response to the spinal cord eluate was absent in trigeminal neurons from TRPV1-knockout mice, and the response in wild-type neurons was blocked by a TRPV1 antagonist. The molecules were isolated and identified as oxidation products of linoleic acid, 9-hydroxyoctadecadienoic acid (9-HODE), 13-HODE, 9-oxoODE, and 12-oxoODE, which are also known to be released under inflammatory conditions. Application of any of these lipid products to trigeminal neurons or to cultured cells transfected with TRPV1 was stimulatory, producing a calcium signal or current, respectively. Injection of 9-HODE into the spinal cord of rats resulted in inflammatory mechanical allodynia (pain in response to touch that would normally not cause pain), which was blocked if coinjected with a TRPV1 antagonist. Injection of an inflammatory agent into the paw also triggered mechanical allodynia, which was reversed if the rats received intraspinal injections of antibodies to neutralize 9-HODE and 13-HODE. Thus, noxious stimuli appear to result in the release of inflammatory lipid products that activate spinal TRPV1 channels to contribute to hyperalgesia.

A. M. Patwardhan, P. E. Scotland, A. N. Akopian, K. M. Hargreaves, Activation of TRPV1 in the spinal code by oxidized linoleic acid metabolites contributes to inflammatory hyperalgesia. Proc. Natl. Acad. Sci. U.S.A. 106, 18820–18824 (2009). [Abstract] [Full Text]

U. Oh, J. N. Wood, Fat location defines sensation. Proc. Natl. Acad. Sci. U.S.A. 106, 18435–18436 (2009). [Full Text]