Gray matter volume and pain tolerance in a general population: the Tromsø study

As pain is processed by an extensive network of brain regions, the structural status of the brain may affect pain perception. We aimed to study the association between gray matter volume (GMV) and pain sensitivity in a general population. We used data from 1522 participants in the seventh wave of the Tromsø study, who had completed the cold pressor test (3°C, maximum time 120 seconds), undergone magnetic resonance imaging (MRI) of the brain, and had complete information on covariates. Cox proportional hazards regression models were fitted with time to hand withdrawal from cold exposure as outcome. Gray matter volume was the independent variable, and analyses were adjusted for intracranial volume, age, sex, education level, and cardiovascular risk factors. Additional adjustment was made for chronic pain and depression in subsamples with available information on the respective item. FreeSurfer was used to estimate vertexwise cortical and subcortical gray matter volumes from the T1-weighted MR image. Post hoc analyses were performed on cortical and subcortical volume estimates. Standardized total GMV was associated with risk of hand withdrawal (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.71-0.93). The effect remained significant after additional adjustment for chronic pain (HR 0.84, 95% CI 0.72-0.97) or depression (HR 0.82, 95% CI 0.71-0.94). In post hoc analyses, positive associations between standardized GMV and pain tolerance were seen in most brain regions, with larger effect sizes in regions previously shown to be associated with pain. In conclusion, our findings indicate that larger GMV is associated with longer pain tolerance in the general population.