Chronic pain in adults with sickle cell disease is associated with alterations in functional connectivity of the brain.

Chronic pain affects 50% of adults with sickle cell disease (SCD). Although central sensitization is thought to contribute to the pathogenesis of this chronic pain, no studies have examined differences in functional connectivity of the brain between patients with SCD with and without chronic pain. We performed an observational cohort study using resting-state functional MRI (rsfMRI) of the brain on adults with SCD with and without chronic pain. We tested the hypothesis that, compared to those without chronic pain, those with chronic pain would have differences in functional connectivity between the periaqueductal grey (PAG) and other regions of the brain. Twenty-two adults with SCD, 15 with chronic pain and 7 without chronic pain, as well as 10 African-American controls, underwent rsfMRI of the brain. When SCD patients with chronic pain were compared to those without chronic pain, significant differences in connectivity were noted between the PAG and 9 regions of the brain, including several in the default mode network, a network involved in introspection that has been implicated in other chronic pain syndromes. Changes in functional connectivity between patients with SCD with and without chronic pain suggest a mechanism for chronic pain that involves neuro-plastic changes to the brain.
Competing Interests: JJF has been a consultant for Ironwood. JJF has received research funds from Ironwood, Prolong, and Incyte. MSK received an honoraria from New Health Sciences, Inc. For the cuurent publication, these funders have played no role in the study design, data collection, data analysis, interpretation of data, writing of the paper, or decision to submit this study for publication. These conflicts do not alter our adherence to PLOS ONE policies on sharing data and materials. No other authors declare a conflict of interest for this manuscript.