Social interaction with a cagemate in pain facilitates subsequent spinal nociception via activation of the medial prefrontal cortex in rats.
Empathy for the pain experience of others can lead to the activation of pain-related brain areas and can even induce aberrant responses to pain in human observers. Recent evidence shows this high-level emotional and cognitive process also exists in lower animals; however, the mechanisms underlying this phenomenon remain unknown. In the present study we found that, after social interaction with a rat that had received subcutaneous injection of bee venom (BV), only the cagemate observer (CO) but not the noncagemate observer (NCO) showed bilateral mechanical hypersensitivity and an enhanced paw flinch reflex following BV injection. Moreover, neuronal activities labeled by c-Fos immunoreactivity in the spinal dorsal horn of CO rats were also significantly increased relative to the control 1 hour after BV injection. A stress-related response can be excluded because serum corticosterone concentration following social interaction with demonstrator rats in pain was not changed in CO rats relative to NCO and isolated control rats. Anxiety can also be excluded because anxiety-like behaviors could be seen in both the CO and NCO rats tested in the open-field test. Finally, bilateral lesions of the medial prefrontal cortex eliminated the enhancement of the BV-induced paw flinch reflex in CO rats, but bilateral lesions of either the amygdala or the entorhinal cortex failed. Together, we have provided another line of evidence for the existence of familiarity-dependent empathy for pain in rats and have demonstrated that the medial prefrontal cortex plays a critical role in processing the empathy-related enhancement of spinal nociception.
Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, PR China Key Laboratory of Brain Stress and Behavior, PLA, Xi'an 710038, PR China Beijing Institute for Brain Disorders, Beijing 100069, PR China.
Zhen
Z
Li
Yun-Fei
YF
Lu
Chun-Li
CL
Li
Yan
Y
Wang
Wei
W
Sun
Ting
T
He
Xue-Feng
XF
Chen
Xiao-Liang
XL
Wang
Jun
J
Chen
D000679:Amygdala; D000818:Animals; D001007:Anxiety; D001522:Behavior, Animal; D004645:Empathy / Q000502:physiology*; D018728:Entorhinal Cortex; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology*; D059225:Nociception / Q000502:physiology*; D020671:Posterior Horn Cells / Q000378:metabolism; D017397:Prefrontal Cortex / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012021:Reflex, Abnormal / Q000502:physiology; D012919:Social Behavior; D013116:Spinal Cord / Q000378:metabolism / Q000502:physiology*
D016760:Proto-Oncogene Proteins c-fos
Empathy; Prosocial behavior; Rats; Spinal nociception; mPFC