Avaliação do papel dos receptores GABAA-benzodiazepínicos da ínsula na nocicepção de camundongos que conviveram com coespecífico em condição de dor crônica

Abstract

Empathy for pain is the ability to feel other’s pain and recent studies suggest this capacity between rodents. GABAergic system has receptors in brain structures involved in emotional processes as the insula, which is known to play a role in modulation of pain and empathy. The present study investigated the role of Benzodiazepine-GABAA system and insula’s Benzodiazepine-GABAA receptors on social modulation of pain induced by cohabiting with a mouse submitted to a neuropathic pain model. The role of GABA system was assessed by systemic treatment of midazolam (MDZ) (0.5, 1.0, 2.0 mg/kg), a GABAA agonist (Exp. 1) and the role of GABAA receptors of insula by MDZ microinjections (3 and 30 nmol/0.1 μl) in the structure (Exp. 2). Male Swiss mice (n=8-10/group) (Ethics: CEUA/UFSCar N° 47520904) were housed in pairs and after 14 days were divided into two groups: cagemate nerve constriction (CNC), in which one animal of each pair was subjected to sciatic nerve constriction and cagemate sham (CS), one animal from each pair was subjected to the same surgery but without constriction. On Experiment 1, in the 28th day of cohabiting, the observer cagemate, who lived with a CS or CNC, received injections of saline or midazolam (0.5, 1.0 and 2.0 mg/kg, subcutaneous, s.c) and, 30 minutes after, were submitted to the writhing test for 5 minutes to evaluate nociception. In Experiment 2, the protocol was the same, but in 23th day of cohabiting, each observer cagemate was surgically implanted with guide cannula bilaterally in the insula. In the 28th day, the observer cagemate received intra-insula injections of saline or midazolam (3 or 30nmol/0.1 μl) and after 10 minutes was submitted to writhing test. In both experiments, two-way ANOVA followed by post hoc Duncan test revealed that the number of writhes was higher in CNC animals than the CS animals (P < 0.05). In Experiment 1, the higher dose of midazolam (2.0 mg/kg) decreased the number of writhes induced by living with a pair in neuropathic pain (P < 0.05), but this response was not changed by intra-insula midazolam (P < 0.05, Experiment 2). Results suggest that cohabitation in pairs with chronic pain condition induces hypernociception and benzodiazepine-GABAA system is possibly involved in the social modulation of pain, but not mechanisms located within the insula.