The search for translational pain outcomes to refine analgesic development: Where did we come from and where are we going? González Cano, Rafael Montilla-García, Ángeles Ruiz Cantero, María del Carmen Bravo Caparrós, Inmaculada Tejada, Miguel Ángel Nieto López, Francisco Rafael Cobos del Moral, Enrique José Analgesia Pain Behavior Animal model Grip strength Postural changes Wheel running Burrowing Nesting Home cage activity Intracranial self-stimulation Exploratory activity Facial expressions Pain measures traditionally used in rodents record mere reflexes evoked by sensory stimuli; the results thus may not fully reflect the human pain phenotype. Alterations in physical and emotional functioning, pain-depressed behaviors and facial pain expressions were recently proposed as additional pain outcomes to provide a more accurate measure of clinical pain in rodents, and hence to potentially enhance analgesic drug development. We aimed to review how preclinical pain assessment has evolved since the development of the tail flick test in 1941, with a particular focus on a critical analysis of some nonstandard pain outcomes, and a consideration of how sex differences may affect the performance of these pain surrogates. We tracked original research articles in Medline for the following periods: 1973-1977, 1983-1987, 1993-1997, 2003-2007, and 2014-2018. We identified 606 research articles about alternative surrogate pain measures, 473 of which were published between 2014 and 2018. This indicates that preclinical pain assessment is moving toward the use of these measures, which may soon become standard procedures in preclinical pain laboratories. 2021-03-11T08:23:07Z 2021-03-11T08:23:07Z 2020-06 info:eu-repo/semantics/article González-Cano R, Montilla-García Á, Ruiz-Cantero MC, Bravo-Caparrós I, Tejada MÁ, Nieto FR, Cobos EJ. The search for translational pain outcomes to refine analgesic development: Where did we come from and where are we going? Neurosci Biobehav Rev. 2020 Jun;113:238-261. http://hdl.handle.net/10481/67089 10.1016/j.neubiorev.2020.03.004 eng MINECO, grant SAF2016-80540-R http://creativecommons.org/licenses/by-nc-nd/3.0/es/ info:eu-repo/semantics/openAccess Atribución-NoComercial-SinDerivadas 3.0 España