O papel da neurotransmissão alfa-2 adrenérgica do córtex cingulado anterior na modulação da ansiedade e da nocicepção na empatia para a dor crônica em camundongos machos e fêmeas.

Abstract

Empathy, defined as the ability to observe and infer the emotional and mental states of others, has been the subject of numerous research studies, and this phenomenon can also be observed in rodents. Studies indicate that cohabitation with a cagemate experiencing chronic pain induces hypernociception and an increase in anxiety-like behaviors, and that the anterior cingulate cortex (ACC) modulates empathy, anxiety, and nociception. Therefore, considering the high density of alpha-2 adrenergic receptors in the ACC and their role in modulating anxiety and pain, this study investigated the involvement of alpha-2 adrenergic neurotransmission within the ACC in modulating nociception and anxiety in the empathy for chronic pain model. Thus, male and female Swiss-albino mice were housed in quartets during a 28-day cohabitation protocol. On the 14th day, one of the animals in the quartet was selected to be the chronic pain demonstrator (CNC) or Sham demonstrator. On day 24, the observer mice (Ob-CNC and Ob-Sham) underwent CCA stereotaxis. On days 26, 27, and 28, a partition was introduced into the housing cage for 15 minutes to induce habituation and enable the abdominal writhing test in Ob-CNC and Ob-Sham mice. On day 28, Ob-CNC and Ob-Sham animals received bilateral intra-CCA injections of saline/clonidine 8 μg/0.1 μL (alpha-2 adrenergic receptor agonist), yohimbine 0.05 μg/0.1 μL (alpha-2 adrenergic receptor antagonist)/saline, yohimbine 0.05 μg/clonidine 8 μg, saline/saline, and were then subjected to the elevated plus maze for 5 minutes. Next, they received an injection of 0.6% acetic acid (10 ml/kg, intraperitoneal) for evaluation of abdominal contortions over 5 minutes. CNC and Sham mice were evaluated in the hot plate test on day 28. Our results showed that cohabitation in quartets with a chronic pain demonstrator induces hypernociception and increased anxiety-like responses in male and female mice. Clonidine (8 μg) reduced hypernociception and decreased anxiety-like behaviors, whereas pre-treatment with yohimbine (0.05 μg) reversed clonidine-induced antinociception without altering anxiety-like behaviors in the observer mice. Hence, alpha-2 adrenergic neurotransmission in the ACC plays a distinct role in modulating nociception and anxiety induced by empathy for chronic pain model in both male and female mice.