Chronic overlapping pain conditions and nociplastic pain

Keira J A Johnston; Rebecca Signer; Laura M Huckins

doi:10.1016/j.xhgg.2024.100381

Chronic overlapping pain conditions and nociplastic pain

HGG Adv. 2024 Nov 4;6(1):100381. doi: 10.1016/j.xhgg.2024.100381. Online ahead of print.

Authors

Keira J A Johnston¹, Rebecca Signer², Laura M Huckins³

Affiliations

¹ Department of Psychiatry, Yale School of Medicine, Yale University, New Haven, CT 06511, USA.
² Department of Genetic and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA.
³ Department of Psychiatry, Yale School of Medicine, Yale University, New Haven, CT 06511, USA. Electronic address: laura.huckins@yale.edu.

PMID: 39497418
DOI: 10.1016/j.xhgg.2024.100381

Abstract

Chronic overlapping pain conditions (COPCs) are a subset of chronic pain conditions commonly comorbid with one another and more prevalent in women and individuals assigned female at birth (AFAB). Pain experience in these conditions may better fit with a new mechanistic pain descriptor, nociplastic pain, and nociplastic pain may represent a shared underlying factor among COPCs. We applied GenomicSEM common-factor genome-wide association study (GWAS) and multivariate transcriptome-wide association (TWAS) analyses to existing GWAS output for six COPCs in order to find genetic variation associated with nociplastic pain, followed by genetic correlation (linkage disequilibrium score regression), gene set, and tissue enrichment analyses. We found 24 independent single nucleotide polymorphisms (SNPs), and 127 unique genes significantly associated with nociplastic pain, and showed nociplastic pain to be a polygenic trait with significant SNP heritability. We found significant genetic overlap between multisite chronic pain and nociplastic pain, and to a smaller extent with rheumatoid arthritis and a neuropathic pain phenotype. Tissue enrichment analyses highlighted cardiac and thyroid tissue, and gene set enrichment analyses emphasized potential shared mechanisms in cognitive, personality, and metabolic traits and nociplastic pain along with distinct pathology in migraine and headache. We used a well-powered network approach to investigate nociplastic pain using existing COPC GWAS output, and show nociplastic pain to be a complex, heritable trait, in addition to contributing to understanding of potential mechanisms in development of nociplastic pain.

Keywords: chronic low back pain; chronic overlapping pain conditions; endometriosis; fibromyalgia; migraine; multivariate GWAS; nociplastic pain; temporomandibular joint disorder.