A GABAergic pathway from dorsal raphe nucleus to paraventricular thalamic nucleus modulates incision-related pain...

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 DRN^GABA-PVT pathway induced nociceptive sensitivity in normal mice, while activation of this pathway alleviated incision pain. Notably, antagonists targeting GABA_A receptors-not GABA_B receptors-administered into the PVT blocked DRN^GABA-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 GABA_A receptors in the PVT.