{"id":53801,"date":"2025-07-09T12:14:14","date_gmt":"2025-07-09T19:14:14","guid":{"rendered":"https:\/\/www.salk.edu\/?post_type=disclosure&p=53801"},"modified":"2025-07-09T15:21:47","modified_gmt":"2025-07-09T22:21:47","slug":"from-injury-to-agony-scientists-discover-brain-pathway-that-turns-pain-into-suffering","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/from-injury-to-agony-scientists-discover-brain-pathway-that-turns-pain-into-suffering\/","title":{"rendered":"\u4ece\u53d7\u4f24\u5230\u75db\u82e6\u79d1\u5b66\u5bb6\u53d1\u73b0\u5c06\u75bc\u75db\u8f6c\u5316\u4e3a\u75db\u82e6\u7684\u5927\u8111\u901a\u8def"},"content":{"rendered":"

LA JOLLA\u2014Pain isn\u2019t just a physical sensation\u2014it also carries emotional weight. That distress, anguish, and anxiety can turn a fleeting injury into long-term suffering.<\/p>\n

Researchers at the Salk Institute have now identified a brain circuit that gives physical pain its emotional tone, revealing a new potential target for treating chronic and affective pain conditions such as fibromyalgia, migraine, and post-traumatic stress disorder (PTSD).<\/p>\n

Published on July 9, 2025, in Proceedings of the National Academy of Sciences<\/em><\/a>, the study identifies a group of neurons in a central brain area called the thalamus that appears to mediate the emotional or affective <\/em>side of pain in mice. This new pathway challenges the textbook understanding of how pain is processed in the brain and body.<\/p>\n

\"From<\/a>
From left: Sukjae Kang and Sung Han
Click here<\/a> for a high-resolution image.
Credit: Salk Institute<\/figcaption><\/figure>\n

\u201cFor decades, the prevailing view was that the brain processes sensory and emotional aspects of pain through separate pathways,\u201d says senior author Sung Han<\/a>, associate professor and holder of the Pioneer Fund Developmental Chair at Salk. \u201cBut there\u2019s been debate about whether the sensory pain pathway might also contribute to the emotional side of pain. Our study provides strong evidence that a branch of the sensory pain pathway directly mediates the affective experience of pain.\u201d<\/p>\n

The physical sensation of pain is what allows you to immediately detect it, assess its intensity, and identify its source. The affective part of pain is what makes it so unpleasant. This emotional discomfort motivates you to take action and helps you learn to associate negative feelings with the situation so you can avoid it in the future.<\/p>\n

This is a critical distinction. Most people start to perceive pain at the same stimulus intensities, meaning we all process the sensory side of pain fairly similarly. In comparison, our ability to tolerate <\/em>pain varies greatly. How much we suffer or feel threatened by pain is determined by our affective processing, and if that becomes too sensitive or lasts too long, it can result in a pain disorder. This makes it important to understand which parts of the brain control these different dimensions of pain.<\/p>\n

Sensory pain was thought to be mediated by the spinothalamic tract, a pathway that sends pain signals from the spinal cord to the thalamus, which then relays them to sensory processing areas across the brain.<\/p>\n

Affective pain was generally thought to be mediated by a second pathway called the spinoparabrachial tract, which sends pain information from the spinal cord into the brainstem.<\/p>\n

However, previous studies using older research methods have suggested the circuitry of pain may be more complex. This long-standing debate inspired Han and his team to revisit the question with modern research tools.<\/p>\n

Using advanced techniques to manipulate the activity of specific brain cells, the researchers discovered a new spinothalamic pathway in mice. In this circuit, pain signals are sent from the spinal cord into a different part of the thalamus, which has connections to the amygdala, the brain\u2019s emotional processing center. This particular group of neurons in the thalamus can be identified by their expression of CGRP (calcitonin gene-related peptide), a neuropeptide originally discovered in Professor \u7f57\u7eb3\u5fb7\u00b7\u57c3\u6587\u65af<\/a>\u2019 lab at Salk.<\/p>\n

\"CGRP-expressing<\/a>
CGRP-expressing neurons (green) in the parvocellular subparafascicular nucleus (SPFp) of the thalamus.
Click here<\/a> for a high-resolution image.
Credit: Salk Institute<\/figcaption><\/figure>\n

When the researchers \u201cturned off\u201d (genetically silenced) these CGRP neurons, the mice still reacted to mild pain stimuli, such as heat or pressure, indicating their sensory processing was intact. However, they didn\u2019t seem to associate lasting negative feelings with these situations, failing to show any learned fear or avoidance behaviors in future trials. On the other hand, when these same neurons were \u201cturned on\u201d (optogenetically activated), the mice showed clear signs of distress and learned to avoid that area, even when no pain stimuli had been used.<\/p>\n

\u201cPain processing is not just about nerves detecting pain; it\u2019s about the brain deciding how much that pain matters,\u201d says first author Sukjae Kang, a senior research associate in Han\u2019s lab. \u201cUnderstanding the biology behind these two distinct processes will help us find treatments for the kinds of pain that don\u2019t respond to traditional drugs.\u201d<\/p>\n

Many chronic pain conditions\u2014such as fibromyalgia and migraine\u2014involve long, intense, unpleasant experiences of pain, often without a clear physical source or injury. Some patients also report extreme sensitivity to ordinary stimuli like light, sound, or touch, which others would not perceive as painful.<\/p>\n

Han says overactivation of the CGRP spinothalamic pathway may contribute to these conditions by making the brain misinterpret or overreact to sensory inputs. In fact, transcriptomic analysis of the CGRP neurons showed that they express many of the genes associated with migraine and other pain disorders.<\/p>\n

Notably, several CGRP blockers are already being used to treat migraines. This study may help explain why these medications work and could inspire new nonaddictive treatments for affective pain disorders.<\/p>\n

Han also sees potential relevance for psychiatric conditions that involve heightened threat perception, such as PTSD. Growing evidence from his lab suggests that the CGRP affective pain pathway acts as part of the brain\u2019s broader alarm system, detecting and responding to not only pain but a wide range of unpleasant sensations. Quieting this pathway with CGRP blockers could offer a new approach to easing fear, avoidance, and hypervigilance in trauma-related disorders.<\/p>\n

Importantly, the relationship between the CGRP pathway and the psychological pain associated with social experiences like grief, loneliness, and heartbreak remains unclear and requires further study.<\/p>\n

\u201cOur discovery of the CGRP affective pain pathway gives us a molecular and circuit-level explanation for the difference between detecting<\/em> physical pain and suffering<\/em> from it,\u201d says Han. \u201cWe\u2019re excited to continue exploring this pathway and enabling future therapies that can reduce this suffering.\u201d<\/p>\n

Other authors include Shijia Liu, Jong-Hyun Kim, Dong-Il Kim, Tae Gyu Oh, Jiahang Peng, Mao Ye, Kuo-Fen Lee, Ronald M. Evans, and Martyn Goulding of Salk.<\/p>\n

The work was supported by the National Institutes of Mental Health (BRAINS grant 1R01MH116203) and the Simons Foundation (Bridge to Independence award SFARI #388708).<\/p>","protected":false},"featured_media":53805,"template":"","faculty":[294],"disease-research":[458,124,465,464],"class_list":["post-53801","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-sung-han","disease-research-anxiety","disease-research-neuroscience-and-neurological-disorders","disease-research-pain","disease-research-perception"],"acf":[],"yoast_head":"\nFrom injury to agony: Scientists discover brain pathway that turns pain into suffering - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/zh\/news-release\/from-injury-to-agony-scientists-discover-brain-pathway-that-turns-pain-into-suffering\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"From injury to agony: Scientists discover brain pathway that turns pain into suffering - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014Pain isn\u2019t just a physical sensation\u2014it also carries emotional weight. 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