Investigating the role of pain-modulating pathway genes in musculoskeletal pain
Holliday, K L × McBeth, J Macfarlane, G Huhtaniemi, I T Bartfai, G Casanueva, F F Forti, G Kula, K Punab, M Vanderschueren, Dirk Wu, F C Thomson, W #
European Federation of Chapters of the International Association for the Study of Pain
European Journal of Pain vol:17 issue:1 pages:28-34
AIMS: The aim of this study was to determine if genetic variation in the pain-modulating gene DREAM and its pathway genes influence susceptibility to reporting musculoskeletal pain in the population. METHODS: Pairwise tag single nucleotide polymorphisms (SNPs) in DREAM, PDYN and OPRK1 were genotyped in a UK population-based discovery cohort in whom pain was assessed using blank body manikins at three time points. Depression and anxiety symptoms were assessed at the first time point. Zero-inflated negative binomial regression was used to test for association between SNPs and the maximum number of pain sites reported (0-29) across the three time points. Significantly associated SNPs (p < 0.05) were subsequently genotyped for validation in a cohort of European men with pain assessed at two time points. RESULTS: Thirty-five SNPs were genotyped in 1055 subjects, of whom 83% reported pain, in the discovery cohort. SNPs in each gene were associated with the maximum number of pain sites reported, were independent of symptoms of anxiety and depression and had a significant cumulative effect (p = 7.0 × 10(-5) ). Significantly associated SNPs were successfully genotyped in 1733 men, 76% of whom reported pain, in the validation cohort, but did not show significant association with the number of pain sites. CONCLUSIONS: Genetic variation in the DREAM pathway genes was associated with the extent of pain reporting in a population-based cohort. These findings were not replicated in a single independent cohort; however, given the potential of this pathway as a therapeutic target, further investigation in additional cohorts is warranted.