Validating Rat Model of Empathy for Pain: Effects of Pain Expressions in Social Partners

Abstract

Pain can be socially transferred between familiar rats due to empathic responses. To validate rat model of empathy for pain, effects of pain expressions in a cagemate demonstrator (CD) in pain on empathic pain responses in a naïve cagemate observer (CO) after 30 min priming dyadic social interactions (PDSI) were evaluated. The CD rats were prepared with four pain models: bee venom (BV), formalin, complete Freund's adjuvant (CFA), and spared nerve injury (SNI). Both BV and formalin tests are characterized by displayable and eye-identifiable spontaneous pain-related behaviors (SPRB) immediately after treatment, while CFA and SNI models are characterized by delayed occurrence of evoked pain hypersensitivity but with less eye-identifiable SPRB. After 30 min PDSI with a CD immediately after BV and formalin, respectively, the empathic mechanical pain hypersensitivity (EMPH) could be identified at both hind paws in CO rats. The BV—or formalin-induced EMPH in CO rats lasted for 4–5 h until full recovery. However, EMPH failed to develop in CO after socially interacting with a CD immediately after CFA, or 2 h after BV when SPRB completely disappeared. The CO's EMPH was partially relieved when socially interacting with an analgecized CD whose SPRB had been significantly suppressed. Moreover, repeated exposures to a CD in pain could enhance EMPH in CO. Finally, social transfer of pain hypersensitivity was also identified in CO who was being co-housed in pairs with a conspecific treated with CFA or SNI. The results suggest that development of EMPH in CO rats would be determined not only by extent of familiarity but also by visually identifiable pain expressions in the social partners during short period of PDSI. However, the visually unidentifiable pain can also be transferred to naïve cagemate when being co-housed in pairs with a distressed conspecific. In summary, the vicariously social contagion of pain between familiar rats is dependent upon not only expressions of pain in social partners but also the time that dyads spent in social communications. The rat model of empathy for pain is a highly stable, reproducible and valid model for studying the neural mechanisms of empathy in lower animals.

Empathic contagious pain and consolation in laboratory rodents: species and sex comparisons

“…3I-L, see supplemental Tables SI-SII for statistical analysis). Although female rats likely had relatively shorter latency than male (p = 0.019, Mann-Whitney U test), no sex difference was seen in time and counts of self-grooming behavior (Fig.2M-N 9 Similar to our previous reports on rats (also see Fig.5C-F) [28][29][30]32], the OCP occurred as well in naive mouse observers from the CO naive -CD pain paradigm after 30 min PDSI (Fig. 4G-L and Fig.…”

“…Evidence for evolutionary issue of empathy From the point of evolutionary view, empathy has been proposed to be hierarchical in mammals that has evolved from very low stage (motor mimicry and emotional contagion) to relatively higher stage (empathic concern and consolation), and finally to the highest stage (perspective-taking, mentalizing, theory of mind and targeted-help) from lower animals to human beings [10]. Although several emerging lines of evidence support existence of emotional contagion in lower mammals [3,11,[41][42][43], answers to the questions about whether lower mammals are able to recognize, understand, share and care others are still controversial due to lack of enough direct experimentally supporting evidence [20,30,44]. In a series of reports associated with empathy for pain in rats and mice including the present study, our lab has provided with strong lines of experimental evidence supporting existence of both emotional contagion and empathic consolation in laboratory rodents [11,[28][29][30][31][32].…”

“…The subjects to serve as an observer should be trained by acclimatizing to hand handling, experimental environment and VCR equipment once daily at least for three days before formal procedures for testing ( Fig.1, for protocol details see [32]). Hand handling was a very important procedure in this study because it could buffer social stress that may block empathy for pain [27,29,30].…”

Rat Model of Empathy for Pain

“…DOI:10.21769/BioProtoc.3266 b. Select pain model for CD rat: according to our previous studies, the BV model (Li et al, 2014 and 2018), the formalin model (Li et al, 2018) Li et al, 2014 and2018;Lü et al, 2017). Among the four CO rats, one fourth showed no change in the PWMT after PDSI with a CD in pain (see animal 4 # ), suggesting no empathy for pain can be seen in someone (see .…”

“…Bio-protocol 9(12): e3266. DOI:10.21769/BioProtoc.3266 manifestations are likely to fail to induce empathic behavior in familiar observers following 30min PDSI, such as Complete Freund's adjuvant (CFA) model and the spared nerve injury (SNI) model (Li et al, 2018).…”