The search for translational pain outcomes to refine analgesic development: Where did we come from and where are we going?
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AuthorGonzález-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
AnalgesiaPainBehaviorAnimal modelGrip strengthPostural changesWheel runningBurrowingNestingHome cage activityIntracranial self-stimulationExploratory activityFacial expressions
González-Cano, R., Montilla-García, Á., Ruiz-Cantero, M. C., Bravo-Caparrós, I., Tejada, M. Á., Nieto, F. R., & Cobos, E. J. (2020). The search for translational pain outcomes to refine analgesic development: where did we come from and where are we going?. Neuroscience & Biobehavioral Reviews. [https://doi.org/10.1016/j.neubiorev.2020.03.004]
SponsorshipM.C. Ruiz Cantero was supported by an FPU grant from the Spanish Ministry of Education, Culture and Sports. M. Tejada was supported by the Ramon Areces Foundation. This study was partially supported by the Spanish Ministry of Economy and Competitiveness, MINECO (grant SAF2016-80540-R), the Junta de Andalucia (grant CTS 109), the University of Granada (grant PPJIB2019.11) and funding from Esteve and the European Regional Development Fund (ERDF). We thank K. Shashok for improving the use of English in the manuscript. The authors thank Mark Richardson for providing the picture of the mouse in the running wheel. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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.