Altered Pain in the Brainstem and Spinal Cord of Fibromyalgia Patients During the Anticipation and Experience of Experimental Pain

Abstract

Chronic pain associated with fibromyalgia (FM) affects a large portion of the population but the underlying mechanisms leading to this altered pain are still poorly understood. Evidence suggests that FM involves altered neural processes in the central nervous system and neuroimaging methods such as functional magnetic resonance imaging (fMRI) are used to reveal these underlying alterations. While many fMRI studies of FM have been conducted in the brain, recent evidence shows that the changes in pain processing in FM may be linked to autonomic and homeostatic dysregulation, thus requiring further investigation in the brainstem and spinal cord. Functional magnetic resonance imaging data from 15 women with FM and 15 healthy controls were obtained in the cervical spinal cord and brainstem at 3 tesla using previously established methods. In order to investigate differences in pain processing in these groups, participants underwent trials in which they anticipated and received a predictable painful stimulus, randomly interleaved with trials with no stimulus. Differences in functional connectivity between the groups were investigated by means of structural equation modeling. The results demonstrate significant differences in brainstem/spinal cord network connectivity between the FM and control groups which also correlated with individual differences in pain responses. The regions involved in these differences in connectivity included the LC, hypothalamus, PAG, and PBN, which are known to be associated with autonomic homeostatic regulation, including fight or flight responses. This study extends our understanding of altered neural processes associated with FM and the important link between sensory and autonomic regulation systems in this disorder.

Keywords: brainstem; chronic; fMRI; fibromyalgia; human; pain; spinal cord.

Figure 1

Anatomical model of the regions and connections used for the structural equation modeling (SEM) analysis.

Figure 2

Connection details for 4 example connections obtained from ANCOVA results for both the Expectation and Stimulation periods, comparing main effects of group (FM vs. HC), main effects of normalized pain score, and group x pain score interaction effects. Source regions are denoted with (s) while target regions are denoted with (t). Red points represent individual participants with fibromyalgia while blue points represent the healthy controls. For each figure, the x axis shows the individual average pain intensity ratings for the stimulus while the y axis shows the individual connectivity strengths (calculated and represented as a β value).