Dissecting the neurogenetic architecture of chronic pain: A brain-wide genetics study

IF 4 2区医学 Q1 CLINICAL NEUROLOGY

Journal of Pain Pub Date : 2025-09-14 DOI:10.1016/j.jpain.2025.105562

Jinyang Gao , Yansong He , Benjin Li , Yanqing Wang

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引用次数: 0

Abstract

Chronic pain (CP) is a widespread and debilitating condition with complex neurobiological and genetic foundations. To better understand the brain-based and genetic mechanisms underlying CP, we integrated bidirectional Mendelian randomization (MR), local genetic correlation analysis (LAVA), and multi-trait colocalization (HyPrColoc) using data from 3935 brain imaging-derived phenotypes (IDPs). CP was characterized using three definitions: multisite chronic pain (MCP), chronic widespread pain (CWP), and general chronic pain (GCP). MR analyses highlighted several brain IDPs, cortical areas such as the anterior cingulate, superior frontal, and inferior frontal gyri, as having potential causal effects on CP risk. Additional findings pointed to the role of resting-state connectivity and cerebellar white matter microstructure. LAVA results indicated local genetic correlations between brain features and CP in regions involved in synaptic remodeling, immune-inflammatory activity, and neurodevelopment. Multi-trait colocalization pinpointed the shared variant - rs1873914, potentially linking CP, IDPs, and SUOX gene expression. Together, these findings suggest that some brain structures and their functions may play a causal role in the development of chronic pain.

Perspective

This study integrates brain imaging phenotypes with genetic analyses to clarify causal links in chronic pain. By combining MR, LAVA, and HyPrColoc, we identify structural and functional brain features, pathways, and candidate genes that may underlie pain chronification, offering targets for mechanistic studies and interventions.

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剖析慢性疼痛的神经遗传学结构：全脑遗传学研究。

慢性疼痛（CP）是一种广泛存在的衰弱性疾病，具有复杂的神经生物学和遗传基础。为了更好地理解CP的脑机制和遗传机制，我们利用来自3935个脑成像衍生表型（IDPs）的数据，整合了双向孟德尔随机化（MR）、局部遗传相关分析（LAVA）和多性状共定位（HyPrColoc）。CP的特征有三个定义：多部位慢性疼痛（MCP）、慢性广泛性疼痛（CWP）和全身慢性疼痛（GCP）。MR分析强调了几个脑IDPs，皮质区域，如前扣带、额上回和额下回，对CP风险有潜在的因果影响。其他研究结果指出静息状态连接和小脑白质微观结构的作用。所有CP定义共有14个idp。LAVA结果表明，脑特征与CP在突触重塑、免疫炎症活性和神经发育相关区域之间存在局部遗传相关性。多性状共定位确定了两个共享变异，rs13107325和rs1873914，可能与CP、IDPs和SUOX基因表达有关。总之，这些发现表明，某些大脑结构及其功能可能在慢性疼痛的发展中起因果作用。观点：这项研究将脑成像表型与遗传分析结合起来，以阐明慢性疼痛的因果关系。通过结合MR、LAVA和HyPrColoc，我们确定了可能导致疼痛慢性化的大脑结构和功能特征、途径和候选基因，为机制研究和干预提供了靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Pain 医学-临床神经学

CiteScore

6.30

自引率

7.50%

发文量

441

审稿时长

42 days

期刊介绍： The Journal of Pain publishes original articles related to all aspects of pain, including clinical and basic research, patient care, education, and health policy. Articles selected for publication in the Journal are most commonly reports of original clinical research or reports of original basic research. In addition, invited critical reviews, including meta analyses of drugs for pain management, invited commentaries on reviews, and exceptional case studies are published in the Journal. The mission of the Journal is to improve the care of patients in pain by providing a forum for clinical researchers, basic scientists, clinicians, and other health professionals to publish original research.