Avaliação do envolvimento da neurotransmissão vasopressinérgica da amígdala na empatia relacionada à nocicepção e ansiedade em camundongos machos e fêmeas

Abstract

Social interaction is a necessary factor for human survival and depends on the ability to understand the intentions and emotions of others, characteristics associated with empathy, which can be observed in humans and other animals. Living with a conspecific with neuropathic pain induces increased anxiety and hypernociception in observer mice (Ob), and the amygdala is one of the structures involved in the modulation of nociception and empathic responses. Vasopressin is a neuropeptide, an agonist of V1A, V1B, and V2 receptors, and atosiban is an antagonist involved in modulating social repertoires, anxiety-like responses, and nociception. In this sense, we demonstrated that systemic injections of vasopressin reversed the hypernociception induced by cohabitation with chronic pain in male mice. The aim of this study was to evaluate the involvement of the amygdala's vasopressinergic system in nociception-related empathy in male and female mice that cohabited with a conspecific experiencing chronic pain. Male and female Swiss-albino mice were housed in quartets, and on the 14th day of cohabitation, one animal from the quartet underwent sciatic nerve constriction surgery (CNC) or not (Sham), returning to cohabitation with their respective observers (Ob-CNC and Ob-SH) for another 14 days. On the 24th day, the mice, male or female (Ob-CNC and Ob-SH), underwent stereotaxy for bilateral implantation of cannulas directed to the amygdala. On day 28, all Ob-CNC and Ob-SH animals received bilateral intra-amygdala injections of vasopressin (1.0 µg/0.1 µL, Experiment 1) and atosiban (V1a receptor antagonist, 0.04 and 0.4 µg/0.1 µL, Experiment 2), and after five minutes were subjected to the elevated plus maze (EPM) for 5 minutes. At the end of the EPM test, they received an intraperitoneal (i.p.) injection of acetic acid (0.6%, 0.1 ml/10 g) and returned to the housing box with their respective CNC and Sham partner for recording the number of abdominal contortions for 5 minutes. The hot plate test was performed on the respective CNC and Sham partners before sciatic nerve constriction surgery (day 14), and after the abdominal writhing test (day 28) to confirm the effectiveness of the surgery and the observers' interaction with the nociceptive animal. The results demonstrated that interaction with the conspecific with chronic pain promoted hypernociception and increased anxiety responses in the pain observers. Intra-amygdala administration of vasopressin (1.0 µg) and atosiban (0.4 µg) reversed the hypernociceptive and anxiety-like effects in male and female observer mice. However, the lower dose of atosiban (0.04 µg) was ineffective in altering the nociceptive response. Intra-amygdala administration of vasopressin produced an anxiolytic-like effect in both male and female observer mice, whereas a higher dose of atosiban (0.4 µg) was effective only in male mice. These findings suggest that amygdalar vasopressinergic neurotransmission modulates emotional and nociceptive processing in male and female mice during emotional pain contagion induced by cohabitation with a conspecific with chronic neuropathic pain.