97: Anterior Paraventricular Thalamus Gates Mechanical Pain via PKC Delta Neurons in the Oval BNST

Topic: Basic Science
Subtopic: Non-specific to any diagnosis (including studies in healthy animals), Neurocircuit modulation (could include opto, DREADDs), Animal imaging (includes Ca2+ imaging, fluorescence microscopy)

Background and Aims: Our previous studies found that activation of the anterior paraventricular thalamus (PVA) → bed nucleus of the stria terminalis (BNST) pathway can induce mechanical hypersensitivity. However, it remains unknown how genetically defined neurons in the oval BNST (ovBNST) mediate this effect and how persistent mechanical hypersensitivity is maintained.

Methods: We investigated PVA inputs to PKCδ- and somatostatin (SOM)-expressing neurons in the oval BNST (ovBNST) following formalin-induced inflammatory pain. TRAPing was used to label PVA-activated neurons. pERK and cFos immunostaining were performed to further map neuronal activation. Functional effects were assessed using in vivo calcium imaging, electrophysiology, optogenetic manipulations, and behavioral assays.

Results: Optogenetic stimulation of anterior paraventricular thalamus inputs increased evoked EPSCs in the oval bed nucleus of the stria terminalis, while spontaneous EPSCs were elevated in PKC Delta neurons but reduced in somatostatin neurons, indicating preferential recruitment of PKC Delta cells. Optogenetic activation of PKC Delta neurons induced mechanical hypersensitivity, whereas activation of somatostatin neurons alleviated pain. In vivo calcium imaging showed persistent PKC Delta activation and inhibition of somatostatin neurons after formalin injection. PKC Delta responses to von Frey stimulation progressively increased from 2 hours to 6 days post-formalin, peaking at day 3, reflecting transient local circuit remodeling.

Conclusions: These findings reveal a previously unknown PVA → ovBNST PKCδ circuit as a critical gating mechanism for mechanical hypersensitivity. Preferential recruitment of PKCδ neurons by PVA inputs underlies transient network reorganization in the BNST during inflammatory pain, highlighting a cell-type- and pathway-specific mechanism for sustained mechanical hypersensitivity.

References: Mindaye SA, Chen WH, Lin SC, Chen YC, Abdelaziz MA, Tzeng YS, Shih AC, Chen SY, Yang SB, Chen CC. 2024. Separate anterior paraventricular thalamus projections differentially regulate sensory and affective aspects of pain. Cell Reports. 43(11):114946.

Presenting Author: Weihsin Chen
Submitting Author: Wei-hsin Chen

Senior Author: Chien-Chang Chen

IASP 2026 Global Year theme of Neuropathic Pain: No

• Yong-Cyuan Chen: Master - Institute of Biomedical Sciences, Academia Sinica
• Chien-Chang Chen: PhD - Institute of Biomedical Sciences, Academia Sinica