Background & Aims

Visceral pain and somatic pain are both unpleasant sensations that act as protective mechanisms against external threats. Although closely related, these sensations are fundamentally distinct, driving unique behavioral responses. Accumulated evidence has confirmed that paraventricular hypothalamus (PVH) plays an important role in the development of visceral pain and somatic pain, whereas the exact mechanisms of action such as the neural pathways and molecules that specifically recognize and encode the two types of pain remain largely unknown.

Methods

Tet-off system combined with c-Fos staining was performed to identify cell populations specifically associated with visceral or somatic pain. Fiber photometry was carried out to detect calcium activity. Chemogenetics was performed to manipulate neuronal excitability. Function-dependent laser capture microdissection followed by RNA sequencing (fLCM-Seq) was used to screen molecular targets specific for visceral or somatic pain. Colorectal distension (CRD) and von Frey fiber (VFF) were used to assess visceral pain and somatic pain behaviors, respectively. Immunofluorescence staining was performed to detect P2X3R/VIPR2 expression and localization.

Results

(1) Representation of visceral and somatic pain by distinct neural ensembles in the PVH. (2) Distinct transcriptional profiles in the CRD-labeled and the VFF-labeled PVH neural ensembles. (3) PVH-lateral septal nucleus (LSV) and PVH-caudal part of Zona Incerta (ZIC) neural circuits specifically respond to visceral and somatic pain stimulation, respectively. (4) Manipulation of the projections from CRD or VFF-labeled PVH neurons to the LSV or ZIC specifically modulates visceral or somatic pain. (5) PVHP2X3R+-LSV circuit regulates visceral pain, whereas PVHVIPR2+-ZIC circuit regulates somatic pain.

Conclusions

Our data unveiled a distinct representation of visceral and somatic pain by unique PVH neuronal ensembles and suggested that PVH as a pain sorting center that distinctly processes visceral and somatic pain through different molecular and neural circuits, providing a new framework for comprehending how the brain processes nociceptive information and identifying potential molecular targets for specific pain processing.

References

1.Cohen, S.P., Vase, L. & Hooten, W.M. Chronic pain: an update on burden, best practices, and new advances. Lancet 397, 2082-2097 (2021).
2. Van Oudenhove, L., et al. Common and distinct neural representations of aversive somatic and visceral stimulation in healthy individuals. Nature communications 11, 5939 (2020).

Presenting Author

Guang-Yin Xu

Poster Authors

Yong-Chang Li

Ph.D.,MD

Institute of Neuroscience, Soochow University

Lead Author

Fu-Chao Zhang

Institute of Neuroscience, Soochow University

Lead Author

Guang-Yin Xu

Soochow University

Lead Author

Topics

  • Specific Pain Conditions/Pain in Specific Populations: Acute Pain and Nociceptive Pain