Research ReportPain and stress functional evidence that supra-spinal mechanisms involved in pain-induced analgesia mediate stress-induced analgesiaTobaldini, Glauciaa,,b; Andersen, Erik O.L.a; Polato, Jhuliana J.a; Guilhen, Vinicius A.a; Gaspar, Jessica C.a; Lazzarim, Mayla K.a; Sardi, Natalia F.a; Fischer, LuanaaAuthor Information aDepartment of Physiology, Division of Biological Sciences, Federal University of Parana, Curitiba bPositivo University, Curitiba, Parana, Brazil Received 19 October 2018 Accepted as revised 16 October 2019 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website, www.behaviouralpharm.com. Correspondence to Luana Fischer, PhD, Department of Physiology, Division of Biological Sciences, Federal University of Parana, Av. Francisco H. dos Santos, Centro Politécnico, Postal: 81531-980, Curitiba, Parana, Brazil, E-mail: firstname.lastname@example.org Behavioural Pharmacology: April 2020 - Volume 31 - Issue 2&3 - p 159-167 doi: 10.1097/FBP.0000000000000529 Buy SDC Metrics Abstract Analgesia induced by stressful and painful stimuli is an adaptive response during life-threatening situations. There is no evidence linking the mechanisms underlying them, while the former depends on the activation of stress-related brain pathways, the second depends on opioidergic mechanisms in the nucleus accumbens and on nicotinic cholinergic mechanisms in the rostral ventromedial medulla. In this study, we hypothesized that stress-induced analgesia is also dependent on opioidergic mechanisms in the nucleus accumbens and on nicotinic cholinergic mechanisms in the rostral ventromedial medulla. We used immobilization, a classical procedure to induce acute stress, and evaluated its ability to decrease the nociceptive responses induced either by carrageenan or by formalin in rats. Immobilization stress significantly decreased either carrageenan-induced hyperalgesia or formalin-induced tonic nociception in a time-dependent manner. This stress-induced analgesia is similar to pain-induced analgesia, as revealed by contrasting the antinociceptive effect induced by immobilization and by a forepaw injection of capsaicin. The administration of a µ-opioid receptor antagonist (CTOP, 0.5 µg) into the nucleus accumbens, as well as that of a nicotinic cholinergic receptor antagonist (mecamylamine, 0.6 µg) into the rostral ventromedial medulla, blocked immobilization stress-induced analgesia in both pain models. These results demonstrate that supraspinal mechanisms which are known to mediate pain-induced analgesia also mediate stress-induced analgesia. Therefore both forms of analgesia have overlapping mechanisms, probably recruited in response to the perception of danger. Copyright © 2020 YEAR Wolters Kluwer Health, Inc. All rights reserved.