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Peripheral gating of pain signals by endogenous lipid mediators

An Erratum to this article was published on 26 August 2014

This article has been updated

Abstract

Primary sensory afferents and their neighboring host-defense cells are a rich source of lipid-derived mediators that contribute to the sensation of pain caused by tissue damage and inflammation. But an increasing number of lipid molecules have been shown to act in an opposite way, to suppress the inflammatory process, restore homeostasis in damaged tissues and attenuate pain sensitivity by regulating neural pathways that transmit nociceptive signals from the periphery of the body to the CNS. Here we review the molecular and cellular mechanisms that contribute to the modulatory actions of lipid mediators in peripheral nociceptive signaling.

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Figure 1: Peripheral gating of nociceptive signals by endogenous lipid mediators.
Figure 2: Endocannabinoid control of peripheral nociception.
Figure 3: Formation and deactivation of endocannabinoid lipid mediators.
Figure 4: Formation and deactivation of PEA and OEA.
Figure 5: Control of peripheral nociception by endogenous agonists of peroxisome proliferator-activated receptor-α (PPAR-α).
Figure 6: Biosynthetic pathways for analgesic PUFA-derived mediators.

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Change history

  • 18 March 2014

    In the version of this article initially published, the phosphoanandamide in Figure 3a terminated in a hydroxyl instead of a phosphate group. The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

The authors thank B.D. Hammock, A.G. Hohmann and C.N. Serhan for thoughtful discussions. Work in D.P.'s laboratory is funded in part by grants from the American Asthma Foundation and the National Institute on Drug Abuse, one of the US National Institutes of Health.

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Correspondence to Daniele Piomelli.

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The authors are inventors in patent applications filed by the University of California, Irvine and the Fondazione Istituto Italiano di Tecnologia, which disclose pharmaceutical agents targeting molecular pathways described in the present article.

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Piomelli, D., Sasso, O. Peripheral gating of pain signals by endogenous lipid mediators. Nat Neurosci 17, 164–174 (2014). https://doi.org/10.1038/nn.3612

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