121: Interoception and pain

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic primary orofacial pain, , , , Non-pharmacological interventions, Animal imaging (includes Ca2+ imaging, fluorescence microscopy), Behavioral studies, , , , ,

Background and Aims: Interoception, the sense of the body's physiological condition, is mediated by vagal afferents, which are connected to major parasympathetic efferents leading to the maintenance of bodily homeostasis. Although interoceptive vagal inputs are well known to regulate pain, the neurobiological mechanisms by which vagal activity modulates chronic pain are not well understood. Increasing interoceptive inputs through electrical stimulation of the vagus nerve treats intractable chronic pain and emotional disorders, such as depression. However, vagal inputs can be also pro-nociceptive and can aggravate pathological pain. Therefore, identifying subtypes of vagal afferents responsible for anti-nociception is a critical hurdle for developing more effective and novel analgesic approaches. Temporomandibular disorder (TMD) is a prevalent cause of chronic pain, for which treatment is challenging. Temporomandibular joint (TMJ) is unique, because, unlike other joints, TMJ is directly innervated by vagal afferents.

Methods: We asked if vagus nerve stimulation (VNS) modulated temporomandibular disorder (TMD)-related pain. We found that VNS does modulate TMD, and we identified vagal afferent populations underlying this effect. Targeted chemogenetic activation of specific vagal afferent subtypes profoundly attenuated pain-like behaviors after TMJ injury induced by forced mouth opening (FMO). Furthermore, in vivo intact trigeminal ganglia (TG) GCaMP Ca2+ imaging showed that chemogenetic activation of specific vagal afferents decreased peripheral sensitization of TG neurons after FMO, suggesting

Results: Using a mouse model of TMD, FMO, we showed that auricular VNS (aVNS) attenuates temporomandibular joint (TMJ) pain behaviors and suppresses sensitization of trigeminal nociceptors. We further identified a distinct subset of vagal sensory afferents with dopaminergic-like features that is sufficient to mediate these analgesic effects. Selective activation of these afferents originating from the TMJ region recapitulates the pain-relieving effects of aVNS.

Conclusions: These findings reveal a previously unrecognized peripheral interoceptive pathway through which defined vagal sensory afferents regulate trigeminal pain, thereby establishing a cellular and mechanistic framework for precision neuromodulation strategies targeting chronic TMD-related craniofacial pain.

References: Son H, H. D., Li T, Shannonhouse J, Kim E, Zhou C, Ali M, Baroya N, Chung MK and Kim YS. Vagal dopaminergic afferents link interoception to trigeminal pain modulation. BioRxiv 2026/714928 (2026).

Presenting Author: Yu Shin Kim
Submitting Author: Yu Shin Kim

Senior Author: Yu Shin Kim

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Hyeonwi Son - UAB
• Deoksoo Han - UAB
• Tingting Li - UMB
• John Shannonhouse - UAB
• Eungyung Kim1 - UAB
• Cindy Zhou - UMB
• Md Sams Sazzad Ali - UMB
• Noreen Baroya - UMB
• Man-Kyo Chung - University of Maryland at Baltimore