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. 2025 Jul 15;122(28):e2505889122.
doi: 10.1073/pnas.2505889122. Epub 2025 Jul 9.

Thalamic CGRP neurons define a spinothalamic pathway for affective pain

Sukjae J Kang  1 , Shijia Liu  1 , Jong-Hyun Kim  1 , Dong-Il Kim  1 , Tae Gyu Oh  2 , Jiahang Peng  1 , Mao Ye  1 , Kuo-Fen Lee  1 , Ronald M Evans  2 , Martyn Goulding  3 , Sung Han  1   4   5
Affiliations

Thalamic CGRP neurons define a spinothalamic pathway for affective pain

Sukjae J Kang et al. Proc Natl Acad Sci U S A. .

Abstract

Pain is both a sensory and emotional experience caused by various harmful stimuli. While numerous studies have explored peripheral and central pain mechanisms, the specific neural circuits linking the spinal cord to the brain remain poorly defined. In this study, we demonstrate the involvement of calcitonin gene-related peptide (CGRP)-positive neurons in the parvicellular part of the subparafascicular nucleus (SPFp) in pain. Tracing revealed that CGRP neurons in the SPFp (CGRPSPFp) receive projections from the dorsal horn. Increased calcium activity was observed in CGRPSPFp neurons during mechanical, thermal, and inflammatory stimuli. Genetic silencing of these neurons resulted in reduced pain responses in animals. Furthermore, optogenetic activation of CGRPSPFp neurons induced aversive memory but did not alter mechanical or thermal pain thresholds. This study reveals a distinct neural circuit involving CGRPSPFp neurons that mediates pain, which differs from CGRP neurons in the parabrachial nucleus. Understanding these circuits could lead to better pain treatments with fewer side effects.

Keywords: CGRP; affective pain; pain; thalamus.

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Conflict of interest statement

Competing interests statement:The authors declare no competing interest.

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