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Empathy involves integrated affective and cognitive processes to share the emotional state of others. This evolutionarily conserved ability has also been identified in nonhuman primates and rodents. Our previous work demonstrated that social interaction with a cagemate rat in pain induces mechanical pain hypersensitivity in cagemate observer (CO) rats. Moreover, we also demonstrated that the medial prefrontal cortex (mPFC) and the locus coeruleus-norepinephrine (LC-NE) system are involved in this process. The LC sends noradrenergic innervations throughout the brain, and its innervation of the prefrontal cortex plays important roles in working memory and attention. The present study seeks to study the roles of the LC-to-mPFC pathway in pain empathy in rats. Selective ablation of the noradrenergic innervations of the mPFC through bilateral injections of the axonally transported catecholamine immunotoxin, saporin-conjugated antiserum to dopamine-β-hydroxylase into the mPFC diminished mechanical pain hypersensitivity in CO rats. Bilateral intra-mPFC applications of the adrenergic α1 receptor antagonist prazosin and the β receptor antagonist propranolol, but not the adrenergic α2 antagonist yohimbine, eliminated mechanical pain hypersensitivity in CO rats. In contrast, intra-mPFC applications of prazosin, yohimbine or propranolol did not affect the mechanical pain sensitivity of rats per se. Our results indicate that noradrenergic innervations in the mPFC mediate empathy for pain in rats via the α1 and β receptors., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Empathy, which is a highly cognitive and emotional process, is the ability to share the emotional states of others. Empathy has also been observed in rodents. The empathic sharing of the distressful experience of a conspecific can even motivate altruistic behaviors, which are critical for survival. However, previous studies investigating empathy or prosocial behaviors in rodents mainly employed fearful or other stressful stimuli to elicit emotional changes; whether pain empathy can also motivate prosocial behaviors has yet to be investigated. By using the writhing test, the present study found that cagemate observer (CO) rats, compared with non-cagemate observer (NCO) rats, increased partner-directed grooming (allogrooming) toward conspecifics that had received an intraperitoneal injection of acetic acid during a dyadic social interaction. Following a dyadic social interaction with a demonstrator that received an intraperitoneal injection of acetic acid, the CO rats, compared with NCO rats, exhibited bilateral mechanical pain hypersensitivity and an enhanced acetic acid-induced writhing response. Our results here provided further evidence of pain empathy in rats, suggesting that empathy for pain may motivate prosocial behaviors in rats., (Copyright © 2017 Elsevier B.V. All rights reserved.)