Thalamic CGRP neurons define a spinothalamic pathway for affective pain

• 成果类型: Article
• 署名作者: Kang, Sukjae J.; Liu, Shijia; Kim, Jong-Hyun; Kim, Dong-Il; Oh, Tae Gyu; Peng, Jiahang; Ye, Mao; Lee, Kuo-Fen; Evans, Ronald M.; Goulding, Martyn; Han, Sung
• 署名单位: Salk Institute; Salk Institute; Salk Institute; Institute for Basic Science - Korea (IBS); Sungkyunkwan University (SKKU); Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Institute for Basic Science - Korea (IBS); University of Oklahoma System; University of Oklahoma Health Sciences Center; University of California System; University of California San Diego
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13792
• DOI: 10.1073/pnas.2505889122
• 发表日期: 2025-07-15
• 关键词: congenital insensitivity; molecular-mechanisms; neural circuit; tract neurons; nucleus; responses; rat; identification; projections; asymbolia

摘要

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 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.