Editors' ChoicePain

Resolvins Balm Your Pain in Flesh and Brain

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Science Translational Medicine  05 May 2010:
Vol. 2, Issue 30, pp. 30ec71
DOI: 10.1126/scitranslmed.3001225

Most of us have experienced severe pain at some time in our lives, such as when that wisdom tooth was inflamed and needed to come out. Such pain caused by inflammation can be controlled with nonsteroidal anti-inflammatory drugs, with one caveat: These analgesics decrease not only inflammatory mediators but also molecules that resolve the inflammation. When nonsteroidals no longer alleviate pain, opioids can be a godsend because they halt virtually all pain. But these drugs also have drawbacks in the form of their myriad side effects: dependency, abuse, sedation, nausea, respiratory arrest, and constipation, to name a few. Enter the "resolvins"—a novel class of lipid mediators that are derived from omega-3 fatty acids and resolve inflammation. New work by Xu et al. now reveals that resolvins block pain through both peripheral and central nervous system mechanisms.

First, the authors induced acute inflammatory pain through the injection of irritants such as formalin into the foot sole of mice. When resolvins were delivered into the spinal canals of the mice’s central nervous systems, pain was greatly relieved. In fact, resolvins achieved this relief at much lower doses than did nonsteroidal anti-inflammatory drugs or opioids. In the periphery (specifically, in the foot sole), resolvins suppressed the release of inflammatory cytokines such as tumor necrosis factor (TNF), which is a well-characterized mediator of pain perception through its effects on the central nervous system. Within the spinal cord, the analgesic effects of the resolvins required G protein–coupled receptors because pain relief was inhibited in the presence of pertussis toxin but not naltrexone, which is an opioid receptor antagonist. ChemR23 is a recently discovered G protein–coupled receptor that binds resolvins and is expressed in the spinal cord and on inflammatory cells. The authors showed that the knockdown of ChemR23 expression in the spinal cord diminished the pain-alleviating effects of resolvins. Thus, these lipid mediators act both peripherally and centrally to relieve pain. These results may also explain why omega-3 fatty acids, the precursors of the resolvins, display anti-inflammatory and pain-reduction properties in patients with rheumatoid arthritis. On the basis of this work, researchers hope to identify ChemR23 agonists that function as highly efficient pain medications and are better tolerated by patients than opioids

Z.-Z. Xu et al., Resolvins RvE1 and RvD1 attenuate inflammatory pain via central and peripheral actions. Nat. Med. 11 April 2010 (10.1038/nm.2123). [Abstract]

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