Bortsov Andrey V, Parisien Marc, Khoury Samar, Martinsen Amy E, Lie Marie Udnesseter, Heuch Ingrid, Hveem Kristian, Zwart John-Anker, Winsvold Bendik S, Diatchenko Luda
Department of Anesthesiology, Center for Translational Pain Medicine, Duke University, Durham, NC, USA.
Faculty of Dental Medicine and Oral Health Sciences and Department of Anesthesia, Faculty of Medicine and Health Sciences, Alan Edwards Centre for Research on Pain, McGill University; Montreal, QC, Canada.
Pain Rep. 2022 Aug 9;7(5):e1018. doi: 10.1097/PR9.0000000000001018. eCollection 2022 Sep-Oct.
Back pain is the leading cause of disability worldwide. Although most back pain cases are acute, 20% of acute pain patients experience chronic back pain symptoms. It is unclear whether acute pain and chronic pain have similar or distinct underlying genetic mechanisms.
To characterize the molecular and cellular pathways contributing to acute and chronic pain states.
Cross-sectional observational genome-wide association study.
A total of 375,158 individuals from the UK Biobank cohort were included in the discovery of genome-wide association study. Of those, 70,633 (19%) and 32,209 (9%) individuals met the definition of chronic and acute back pain, respectively. A total of 355 single nucleotide polymorphism grouped into 13 loci reached the genome-wide significance threshold (5x10) for chronic back pain, but none for acute. Of these, 7 loci were replicated in the Nord-Trøndelag Health Study (HUNT) cohort (19,760 chronic low back pain cases and 28,674 pain-free controls). Single nucleotide polymorphism heritability was 4.6% (P=1.4x10) for chronic back pain and 0.81% (P=1.4x10-8) for acute back pain. Similar differences in heritability estimates between acute and chronic back pain were found in the HUNT cohort: 3.4% (P=0.0011) and 0.6% (P=0.851), respectively. Pathway analyses, tissue-specific heritability enrichment analyses, and epigenetic characterization suggest a substantial genetic contribution to chronic but not acute back pain from the loci predominantly expressed in the central nervous system.
Chronic back pain is substantially more heritable than acute back pain. This heritability is mostly attributed to genes expressed in the brain.
背痛是全球致残的主要原因。尽管大多数背痛病例是急性的，但20%的急性疼痛患者会出现慢性背痛症状。目前尚不清楚急性疼痛和慢性疼痛是否具有相似或不同的潜在遗传机制。
描述导致急性和慢性疼痛状态的分子和细胞途径。
横断面观察性全基因组关联研究。
英国生物银行队列中的375158名个体被纳入全基因组关联研究的发现阶段。其中，分别有70633名（19%）和32209名（9%）个体符合慢性和急性背痛的定义。共有355个单核苷酸多态性（分为13个位点）达到了慢性背痛的全基因组显著性阈值（5×10），而急性背痛则无。其中，7个位点在北特伦德拉格健康研究（HUNT）队列中得到重复（19760例慢性下背痛病例和28674例无疼痛对照）。慢性背痛的单核苷酸多态性遗传度为4.6%（P = 1.4×10），急性背痛为0.81%（P = 1.4×10 - 8）。在HUNT队列中，急性和慢性背痛的遗传度估计也存在类似差异：分别为3.4%（P = 0.0011）和0.6%（P = 0.851）。通路分析、组织特异性遗传度富集分析和表观遗传学特征表明，主要在中枢神经系统表达的位点对慢性背痛有显著的遗传贡献，而对急性背痛则无。
慢性背痛的遗传度远高于急性背痛。这种遗传度主要归因于大脑中表达的基因。
