Cingulate entries anterior to the nucleus accumbens control the social transfer of pain and analgesia


Social transmission of pain and relief

In mice, pain and fear can be transferred by short social contact from an animal to a viewer. Neurons in a region of the brain called the anterior cingulate cortex in the spectator animal mediate these transfers. However, the specific prior cingulate projections involved in such empathy-related behaviors are unknown. Black-smith et al. found that projections from the anterior cingulate cortex to the nucleus accumbens are necessary for the social transfer of pain in mice (see the perspective of Klein and Gogolla). The fear, however, was mediated by projections from the anterior cingulate cortex to the basolateral amygdala. Interestingly, in animals with pain, analgesia can also be socially transferred.

Science, this issue p. 153; see also p. 122

Structured summary


Empathy, the adoption of the sensory and emotional state of others, plays a vital role in social interactions. Although, historically, empathy was often viewed as an affective-cognitive process experienced only by humans, it is now appreciated that many species, including rodents, exhibit an evolutionary behavioral history of empathy. , such as observational fear. It is therefore possible to begin to define the neural mechanisms that mediate the behavioral manifestations of empathy in species that are optimal for the application of modern tools in circuit neuroscience.


In humans and rodents, the anterior cingulate cortex (ACC) appears to encode information about the affective state of others. However, little is known about downstream ACC targets that contribute to empathy-related behaviors. To address this topic, we optimized a protocol for the social transfer of pain behavior in mice and compared the ACC-dependent neural circuits responsible for this behavior with the ACC neural circuits necessary for the social transfer of two behavioral states. related: analgesia and fear. These behaviors present a key component of empathy, the adoption of the sensory and emotional state of others.


A one-hour social interaction between a spectator mouse and a cagemate with inflammatory pain led to mechanical hyperalgesia in the spectator mouse, which lasted for 4 hours but not 24 hours. This social transfer of pain was also evident after thermal testing and led to affective changes which were detected by a conspecific. Social interaction led to the activation of neurons in ACC and several downstream targets, including the nucleus accumbens (NAc), which was revealed by tracing the monosynaptic rabies virus as being directly connected to the ‘ACC. Bidirectional manipulation of activity in ACC-to-NAc inputs influenced the acquisition of socially transferred pain but not the expression of the mechanical sensitivity used to assay pain thresholds. A behavioral protocol revealed rapid social transfer of analgesia, which also required activity in ACC-to-NAc entries. In contrast, ACC-to-NAc input activity was not required for social fear transfer, which instead required activity in ACC projections to the basolateral amygdala (BLA).


We have established that mice rapidly adopt the sensory-affective state of a social partner, regardless of the value of the information (i.e. pain, fear, or pain relief). We find that ACC generates specific and appropriate empathic behavioral responses through distinct downstream targets. Specifically, ACC-to-NAc input activity is necessary for the social transfer of pain and analgesia, but not the social transfer of fear, which instead requires ACC-to-NAc input activity. BLA. Elucidating the circuit-specific mechanisms that mediate various forms of empathy in experimentally accessible animal models is needed to generate hypotheses that can be evaluated in human subjects using non-invasive testing. A more sophisticated understanding of brain mechanisms of empathy conserved in evolution will also accelerate the development of new therapies for empathy-related deficits associated with a wide range of neuropsychiatric disorders.

Separate ACC neural circuits ensure the social transfer of pain and fear states.

Complete Freund’s Adjuvant (CFA) -induced pain is transferred from cagemates to spectators after a one-hour social interaction. Viewers also exhibit pain relief after interacting with cagemates who suffer from pain and morphine analgesia. Social transfer of pain and analgesia both require ACC-NAc screenings, while social transfer of fear requires ACC screenings to the BLA. Data represent the mean ± SEM; the dotted line indicates the average baseline cutoff for all groups; **P <0.01 and ****P <0.0001.


Empathy is an essential component of social communication, which involves experiencing the sensory and emotional states of others. We observed that a brief social interaction with a mouse experiencing pain or morphine analgesia resulted in the transfer of these experiences to its social partner. Optogenetic manipulations demonstrated that the anterior cingulate cortex (ACC) and its projections to the nucleus accumbens (NAc) were selectively involved in the social transfer of pain and analgesia. In contrast, the ACC → NAc circuit was not necessary for the social transfer of fear, which instead depended on ACC projections to the basolateral amygdala. These results reveal that ACC, an area of ​​the brain heavily involved in human empathic responses, mediates distinct forms of empathy in mice by influencing different downstream targets.

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