Social stress as a trigger for depressive-like behavior and persistent hyperalgesia in mice: study of the comorbidity between depression and chronic pain

Abstract

BackgroundThere is great comorbidity and similarity between chronic pain and major depressive disorders. We have recently shown that 10 days of social defeat stress (SDS) induces hyperalgesia regardless depressive-like behavior in mice. Here we aimed to investigate whether social stress predisposes to chronic pain and, inversely, whether chronic pain predisposes to stress-induced depression. MethodsFirstly, we used the 10 days SDS paradigm in mice followed by a mild protocol of repetitive inflammatory stimulus to evaluate if SDS would predispose to persistent hyperalgesia development. Secondly, we used the intense protocol of repetitive inflammatory stimulus followed by a subthreshold SDS to evaluate if persistent hyperalgesia would predispose to depressive-like behavior of social avoidance. ResultsOur results showed that SDS predispose to chronic pain, since stressed mice injected with PGE2 for 7 days (mild protocol), stimuli normally not sufficient to trigger chronic pain, showed persistent hyperalgesia. Also, we showed that persistent hyperalgesia induced by repetitive inflammatory stimuli predispose to long-lasting depressive-like behavior of social avoidance induced by subthreshold SDS. LimitationsWe did not analyze molecular mechanism associated with chronic pain and depressive-like behavior induced by SDS. However, we hypothesized that SDS and 14 days of PGE2 would generate neuroplasticity on brain areas shared by chronic pain and depression, predisposing to pain chronification and depressive-like behavior, respectively. ConclusionsWe can conclude social stress as a key and a common factor for chronic pain and depression. We can also conclude that SDS predisposes to chronic pain and, inversely, chronic pain predisposes to depressive-like behavior.