TRPV1-expressing neurons in the dorsal raphe nucleus are activated by self or others’ pain

Abstract

The dorsal raphe nucleus (DRN) contains a genetically diverse population of neurons, some of which process nociceptive signals from the peripheral nervous system. Transient receptor potential vanilloid 1 (TRPV1), a receptor for noxious stimuli, is expressed not only in peripheral nerves but also in the brain, including the DRN, and plays a critical role in the nociception. This study investigates whether TRPV1-expressing neurons in the DRN respond to self-pain and socially transmitted pain. To induce pain, mice were injected with either 2.0%-paraformaldehyde (PFA) or phosphate-buffered saline (PBS) into the plantar surface of the hind paw. Mice injected with PFA exhibited significantly increased foot-licking behaviour. Analysis of neural activity revealed that PFA injection resulted in elevated activation of TRPV1-expressing neurons in the DRN, as identified by c-Fos immunoreactivity. These findings indicate that DRN TRPV1-positive neurons are involved in acute nociceptive processing of self-pain. When paired with a Demonstrator mouse receiving a PFA injection, untreated Observer mice exhibited increased allo-grooming behaviour influenced by the Demonstrator's pain. The c-Fos immunohistochemistry showed that TRPV1-positive neurons in the DRN were activated in both Demonstrators and Observers, reflecting responses to self-pain and observed pain, respectively. These results underscore the role of TRPV1-expressing neurons in the DRN in processing both self-generated and socially transmitted pain, which provides new insight into the shared experience of pain. © 2025 International Brain Research Organization (IBRO)