Research ArticlePain

The nicotinic α6 subunit gene determines variability in chronic pain sensitivity via cross-inhibition of P2X2/3 receptors

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Science Translational Medicine  13 May 2015:
Vol. 7, Issue 287, pp. 287ra72
DOI: 10.1126/scitranslmed.3009986

Which receptor underlies chronic pain?

Pain, especially of the chronic variety, is not well controlled by current drugs, and recent clinical trials have been unsuccessful. By seeking genes with expression levels that correlate with a chronic pain–like test in mice, Wieskopf et al. show that we may have set our sights on the wrong target. Nicotinic receptors that contain the α6 subunit were highly expressed when chronic pain was low, and genetic experiments confirmed that this subunit is the cause. The α6 subunit was required for analgesia, whereas the α4 subunit—the target of recent drug development efforts—was not. A human genetic study showing that people with a certain allele in the α6 subunit gene are at increased risk of chronic pain lends confidence in the clinical relevance of these results.

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