# A GABAergic pathway from dorsal raphe nucleus to paraventricular thalamic nucleus modulates incision-related pain behaviour in mice

## TL;DR

A specific brain pathway involving GABAergic neurons from the dorsal raphe nucleus to the paraventricular thalamic nucleus helps reduce post-surgery pain in mice.

## Contribution

The study identifies a novel GABAergic neural circuit that modulates incision-related pain behavior through GABAA receptors in mice.

## Key findings

- Activation of the DRNGABA−PVT pathway alleviates incision pain in mice.
- GABAA receptor antagonists in the PVT block the analgesic effects of this pathway.
- The pathway is enhanced by external nociceptive stimuli and modulates neuronal excitability in the PVT.

## Abstract

Incision pain is a prevalent condition in clinical practice, affecting approximately 50% of patients and significantly diminishing their quality of life. However, the central mechanisms underlying incision pain remain unclear. Here, we established a paw incision model that increased neuronal excitability in the paraventricular thalamic nucleus (PVT). Multiple tracing methods revealed an inhibitory ascending neural pathway from the dorsal raphe nucleus (DRN) to the PVT, with external nociceptive stimuli enhancing the activity of this pathway. Inhibition of the DRNGABA−PVT pathway induced nociceptive sensitivity in normal mice, while activation of this pathway alleviated incision pain. Notably, antagonists targeting GABAA receptors—not GABAB receptors—administered into the PVT blocked DRNGABA−PVT activation and produced significant analgesic effects on incision pain. Collectively, these findings suggest that GABAergic neurons in the DRN play an analgesic role by acting on GABAA receptors in the PVT.

Zhang et al. report that activation of a GABAergic pathway from the dorsal raphe nucleus (DRN) to the paraventricular thalamic nucleus (PVT) alleviates postoperative pain through GABAA receptors. Using retrograde tracing, in vivo calcium imaging, and chemogenetic approaches, they identify this neural circuit as a potential therapeutic target for pain management.

Graphical AbstractFor image description, please refer to the figure legend and surrounding text.