TARGETING IMMUNE-DRIVEN OPIOID ANALGESIA BY SIGMA-1 RECEPTORS: OPENING THE DOOR TO NOVEL PERSPECTIVES FOR THE ANALGESIC USE OF SIGMA-1 ANTAGONISTS Tejada, Miguel Ángel Montilla-García, Ángeles González Cano, Rafael Bravo Caparrós, Inmaculada Ruiz Cantero, María del Carmen Nieto López, Francisco Rafael Cobos del Moral, Enrique José sigma-1 receptors endogenous opioid peptides analgesia immune cells neuro-immune interactions Immune cells have a known role in pronociception, since they release a myriad of inflammatory algogens which interact with neurons to facilitate pain signaling. However, these cells also produce endogenous opioid peptides with analgesic potential. The sigma-1 receptor is a ligand-operated chaperone that modulates neurotransmission by interacting with multiple protein partners, including the µ-opioid receptor. We recently found that sigma-1 antagonists are able to induce opioid analgesia by enhancing the action of endogenous opioid peptides of immune origin during inflammation. This opioid analgesia is seen only at the inflamed site, where immune cells naturally accumulate. In this article we review the difficulties of targeting the opioid system for selective pain relief, and discuss the dual role of immune cells in pain and analgesia. Our discussion creates perspectives for possible novel therapeutic uses of sigma-1 antagonists as agents able to maximize the analgesic potential of the immune system 2021-03-11T13:30:55Z 2021-03-11T13:30:55Z 2018-05 info:eu-repo/semantics/article Tejada MÁ, Montilla-García Á, González-Cano R, Bravo-Caparrós I, Ruiz-Cantero MC, Nieto FR, Cobos EJ. Targeting immune-driven opioid analgesia by sigma-1 receptors: Opening the door to novel perspectives for the analgesic use of sigma-1 antagonists. Pharmacol Res. 2018 May;131:224-230 http://hdl.handle.net/10481/67118 10.1016/j.phrs.2018.02.008 eng MINECO [grant number SAF2016-80540-R] http://creativecommons.org/licenses/by-nc-nd/3.0/es/ info:eu-repo/semantics/openAccess Atribución-NoComercial-SinDerivadas 3.0 España