The Empathy For Pain In Rats And Its Neural Basis

Empathy is an ability to feel the emotional state of others and used to be theinterests of psychological research. With the development of neuroimaging techniques,the neural basis and the underlying mechanisms of empathy has become a new topic.Neuroimaging research showed that the empathy for one kind of emotion in others couldactivate the same brain areas as experiencing the same emotion themselves, implicatingthe empathy for and self-processing of this kind of emotion may share the same neuralbasis. As a kind of senior brain activities, empathy used to be considered as emotion andcognition processes that are unique in humans, while recently, empathy was also found inother animals, not only in monkeys but also in rodents. Investigations on empathy inrodents are generally confined to description of its occurrence, with conditioned stimulusprotocols preferentially adopted, which is an ordinary method in the study of fear, while the neural basis and the underlying mechanisms are seldom reffered to. There is only oneresearch about the empathy for pain in rodents, which demonstrated its occurrence inmice for the first time. When two mice, that were siblings or raised in the same cage,received noxious stimulus concomitantly, their behavioral responses were bothstrengthened compared to when receiving the same noxious stimulus alone. If the twomice were given noxious stimulus of different intensities, their behaviroal responsescould be influenced by each other. Merely observing cagemates experiencing noxiousstimulation could lead to thermal hyperalgesia in the observer mice. The empathy forpain in mice only occurred between siblings or cagemates. Again, this study onlydemonstrated the exsistence of empathy for pain in mice, without further exploration forthe underlying mechanisms. As empathy for pain was found in mice, whether empathyfor pain exsists in rats is not clear, if there were empathy for pain in rats, then what is theneural basis underlying this response, were the neural basis of emotion and cognitionprocess consistent in humans and rats? There is a lot of limitations in human studies, thusanimal models are needed to investigate the underlying mechanisms of empathy for pain.By using the bee venom (BV) model as an inflammatory pain model, the present studyaims to investigate whether empathy for pain existed in rats, if there were, with thisempathy model for pain, the underlying neural basis was further investigated.The results of this study were showed below:Section1The existence of empathy for pain in ratsRats raised in the same or different cages are grouped in pairs, one rat injected withBV into left hindpaw and served as demonstrator, the other rat served as witness and washoused together with the demonstrator for30min, then the demonstrator was injectedwith BV into the left hindpaw, the flinching reflexes following BV injection was counted.Our results showed:1When rats from the same cage were paired for experiments, theflinching reflex of witness was significantly elevated when compared to normal controlrat that received BV injection alone, when rats from different cages were paired forexperiments, the flinching reflex of witness did not differ from normal control rat.2Theflinching reflex of the demonstrator in the first30min following BV injection did not differ from normal control rats, irrespecting that whether the witness was cagemate orstranger.3When comparing the flinching reflexes in the first30min of the demonstratorand witness, the total numbers of flinching reflexes all showed to be increased whenwitness came from cagemates, while for witness from strangers, some witnesses’flinching reflexes showed to be increased and some showed to be decreased compared tothe demonstrator.4After housing together with demonstrator for30min, paw withdrawmechanical threshold was decreased in witness from cagemates, while paw withdrawthermal latency was unaltered both in witnesses from cagemates or strangers.Collectively, Responses to noxious stimulation was increased in witness from cagematesbut not strangers, implicating the existence of empathy for pain in rats.Section2The potential neural basis underlying empathy for pain in ratsAs empathy for pain occurred only between cagemates, rats paired from cagemateswere chose for further investigations. c-Fos is the protein encoded by oncogene c-fos andis expressed scarcely in normal conditions, while when the nervous system wereactivated, the expression of c-Fos could be significantly unregulated, thus the presentstudy employed immunohistochemistry for c-Fos staining to investigate the brain areasactivated by empathy for pain.30min after the witness from cagemates housing togetherwith demonstrator, the witness was then perfused and with whole brain and lumbar spinalcord staining for c-Fos with immunohistochemistry. Our results showed:1After merelyhousing together with the demonstrator for30min, brain areas that showed positivec-Fos staining include AI, auditory cortex, amygdala, hippocampus, mPFC, Ect, Ent,orbital cortex, LSV, motor cortex, PAG, Pir, Pn, PRh, RSD, RSGc, somatosensory cortex,visual cortex, VP, TeA, paraventricular nucleus. Activations of mPFC and AI wereconsistent with human studies for empathy for pain, implicating that rats and humansmay share the same neural basis of empathy for pain. As for activations of visual cortex,olfactory cortex, auditory cortex, Ent and PRh et al., learning and memory for flinchingreflexes in the demonstrator may take place, which may recruit these sensational systemsto get access to the information about the noxious stimulation. Further investigations areneeded to explore the roles of these brain regions in this process.2The expression of c-Fos in the dorsal horn ipsilateral to the injection site was compared between witnessfrom cagemates and normal control rats at the time point of1h following BV injection,the expression of c-Fos was significantly upregulated in witness from cagemates.Section3The mediating roles of ACC on empathy for pain in ratsAs showed in section2, mPFC, Ent, Hippocampus, Orbital cortex, amygdala couldbe activated during the occurrence of empathy for pain. These brain areas are intenselyinterconnected and constitute the frontal-limbic system. To testify whether this systemmediate the empathy for pain in rats, bilateral mPFC, amygdala and Ent were lesioned,respectively. After bilateral lesion of mPFC, rats received surgery and sham treatmentwere housed together for10days for recovery, then rats with mPFC lesion and shamtreatment were paired for experiments, with the former served as witness and later asdemonstrator. Following the experimental procedures mentioned above, the enhancementof noxious responses in witness vanished, while after bilateral lesion of amygdala andEnt, the increment of flinching reflex in witness was not influenced. Previous work inour lab has demonstrated that bilateral lesion of mPFC exerts no effects on the flinchingreflex following BV injection, our results here showed that simply bilateral lesion ofamygdala or entorhinal cortex also had no effects on the flinching reflex following BVinjection. Collectively, the amygdala and Ent in this frontal-limbic system may only beresponsible for the processing of information and then information was transmitted tomPFC, which is in charge of Top-Down control of behavior. Our results here showedmPFC played a key role in the empathy for pain in rats.Conclusions:1. In experiments from rats paired from cagemates, after the witness was housedtogether with the demonstrator, the behavioral responses to noxious stimulationwere significantly enhanced, the paw withdraw mechanical threshold wasdecreased, implicating the existence of empathy for pain in rats from cagemates.2. A series of brain areas could be activated in witness after merely housingtogether with demonstrator for30min, the activations of mPFC and AI wereconsistent with human studies for empathy for pain, implicating the empathy for pain in rats and humans may share the same neural basis.3. After mPFC was lesioned bilaterally, the enhanced flinching reflex in cagematewitness vanished, while bilateral lesion of amygdala and Ent had no such effects,demonstrated the key roles of mPFC in empathy for pain in rats.