Empathy for Pain: Insula Inactivation and Systemic Treatment With Midazolam Reverses the Hyperalgesia Induced by Cohabitation With a Pair in Chronic Pain Condition.

Empathy for pain is the ability to perceive and understand the pain in the other individual. Recent studies suggested that rodents have this social ability. GABAergic system has receptors in the brain structures involved in emotional processes as well as in the insular cortex. This area has been described as an important key in modulation of pain and empathy. The present study has investigated the role of insula and its Benzodiazepine-GABAA system on social modulation of pain induced by cohabiting with a mouse submitted to sciatic nerve constriction, a neuropathic pain model. The insular cortex function was assessed by the structure inactivation (Experiments 1 and 2); the role of GABA system was evaluated by systemic treatment of midazolam (MDZ 0.5, 1, and 2 mg/kg) (Experiment 3); and the role of GABAA receptors of insula were studied by bilateral MDZ (3 and 30 nmol/0.1 µl) microinjections in the structure (Experiment 4). Male Swiss mice were housed in groups or dyads. On dyads, after 14 days of cohabitation they were divided into two groups: cagemate nerve constriction and cagemate sham (CS). After 14 days of familiarity, cagemates were evaluated on the writhing test. For group-housed, insula inactivation did not change nociception. For dyad-housed, cohabiting with a mouse in chronic pain increased the nociceptive response and the insula inactivation has reverted this response. Systemic MDZ attenuated nociception and intra-insula MDZ did not alter it. Our results suggest that cohabitation with a pair in chronic pain induces hypernociception, insula possibly modulates this response and the GABA system is also possibly involved, but not its insular mechanisms.

Preliminary behavioral assessment of cagemates living with conspecifics submitted to chronic restraint stress in mice.

The capacity of rodents to recognize and respond to emotional signs from a conspecific is a valuable adaptive behavior, which provides essential skills for species survival. However, repeated exposure to aversive situations may elicit maladaptive behavioral responses in subjects that experience noxious episodes and their colony members. Previous findings by our group demonstrated that living with a subject in neuropathic pain induces anxiogenic-like behaviors and hypernociception in mice. Whereas chronic pain may be considered a stressful stimulus, we extended our findings on stress-induced emotional transfer. For this purpose, we investigated whether cohabitation with a partner subjected to chronic restraint stress was able to promote alterations in anxiety-like behaviors, pain sensibility and defensive responses. Male Swiss mice were housed in pairs for 14days and then separated into control, stress, and cagemate groups. The stress group was subjected to 14days of restraint stress (1h/day) in the presence of the cagemates, while the pair-housed control group was left undisturbed. A day after last stress session control, stress, and cagemate groups were evaluated using elevated plus maze test, writhing test, and rat exposure test. Results demonstrated that chronic stress attenuated weight gain in the stress group. Moreover, cohabitation with mice subjected to chronic restraint stress induced anxiogenic-like behaviors, pain hypernociception, and alterations in defensive responses in both cagemate and stress groups. These preliminary findings suggest that chronic exposure to aversive stimulus may induce behavioral alterations even in observers.

Mice undergoing neuropathic pain induce anxiogenic-like effects and hypernociception in cagemates.

Rodents can recognize pain-related responses in conspecifics. Therefore, cohabitation with a conspecific animal with chronic pain can potentially promote a stressful situation, which can trigger behavioral changes such as anxiety and depression and alter nociceptive responses. In this study we investigated the effect of cohabitation with a mouse undergoing sciatic nerve constriction (neuropathic pain model). The cagemates were evaluated for nociception (writhing test), anxiety (elevated plus-maze and open field tests), depression (forced swim, tail suspension, and sucrose preference tests), and corticosterone levels. Male Swiss mice were housed in pairs for 14 days, and then divided into three groups: cagemate nerve constriction, in which one animal of each pair was subjected to constriction of the sciatic nerve; cagemate sham, in which one animal from each pair was subjected to the same surgery but without constriction; and control, in which animals were not subjected to any surgical procedure. After 14 days, the cagemates were evaluated using behavioral tests. Social interaction with a conspecific undergoing constriction of the sciatic nerve induced hypernociception and increased anxiety-related responses, whereas in depression tests inconclusive responses and no changes in corticosterone levels were found. In conclusion, cohabitation with suffering conspecifics induces changes in nociceptive responses, as well as in affective responses including anxiety.