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      Dissociation of the Opioid Receptor Mechanisms that Control Mechanical and Heat Pain

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          Abstract

          Delta and mu opioid receptors (DORs and MORs) are inhibitory G protein-coupled receptors that reportedly cooperatively regulate the transmission of pain messages by substance P and TRPV1-expressing pain fibers. Using a DOReGFP reporter mouse we now show that the DOR and MOR are, in fact, expressed by different subsets of primary afferents. The MOR is expressed in peptidergic pain fibers, the DOR in myelinated and nonpeptidergic afferents. Contrary to the prevailing view, we demonstrate that the DOR is trafficked to the cell surface under resting conditions, independently of substance P, and internalized following activation by DOR agonists. Finally, we show that the segregated DOR and MOR distribution is paralleled by a remarkably selective functional contribution of the two receptors to the control of mechanical and heat pain, respectively. These results demonstrate that behaviorally relevant pain modalities can be selectively regulated through the targeting of distinct subsets of primary afferent pain fibers.

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          Author and article information

          Journal
          Cell
          Cell
          Elsevier BV
          00928674
          June 2009
          June 2009
          : 137
          : 6
          : 1148-1159
          Article
          10.1016/j.cell.2009.04.019
          3683597
          19524516
          543617ff-ffda-4f3a-8b92-5ae771f21033
          © 2009

          https://www.elsevier.com/tdm/userlicense/1.0/

          https://www.elsevier.com/open-access/userlicense/1.0/

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