Distinct neural signaling characteristics between fibromyalgia and provoked vestibulodynia revealed by means of functional magnetic resonance imaging in the brainstem and spinal cord

Abstract

Introduction: Fibromyalgia and provoked vestibulodynia are two chronic pain conditions that disproportionately affect women. The mechanisms underlying the pain in these conditions are still poorly understood, but there is speculation that both may be linked to altered central sensitization and autonomic regulation. Neuroimaging studies of these conditions focusing on the brainstem and spinal cord to explore changes in pain regulation and autonomic regulation are emerging, but none to date have directly compared pain and autonomic regulation in these conditions. This study compares groups of women with fibromyalgia and provoked vestibulodynia to healthy controls using a threat/safety paradigm with a predictable noxious heat stimulus.

Methods: Functional magnetic resonance imaging data were acquired at 3 tesla in the cervical spinal cord and brainstem with previously established methods. Imaging data were analyzed with structural equation modeling and ANCOVA methods during: a period of noxious stimulation, and a period before the stimulation when participants were expecting the upcoming pain.

Results: The results demonstrate several similarities and differences between brainstem/spinal cord connectivity related to autonomic and pain regulatory networks across the three groups in both time periods.

Discussion: Based on the regions and connections involved in the differences, the altered pain processing in fibromyalgia appears to be related to changes in how autonomic and pain regulation networks are integrated, whereas altered pain processing in provoked vestibulodynia is linked in part to changes in arousal or salience networks as well as changes in affective components of pain regulation.

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

Figure 1

Task paradigm for the fibromyalgia and provoked vestibulodynia data. Periods of interest that were analyzed in the current study include “Expecting Pain” (centered at 90 s, or 1 min 30 s) and “Experiencing Pain” (centered at 135 s, or 2 min 15 s). While the larger data set also included runs without the painful stimulus, only the runs where the noxious stimulus was applied were analyzed in the current study.

Figure 2

Anatomical model of the regions and connections used for the structural equation modelling (SEM) analysis. Arrow points indicate directions modeled for each connection.

Figure 3

Summary of ANCOVA results showing connections with a significant main effect of group in the expecting pain (left) and experiencing pain (right) timepoint. Connections are color-coded based on which groups were significantly different from each other, as evaluated with post-hoc tests. Black lines indicate connections where no interpretable pattern was found. Details of all connections are available in Table 2 for reference.

Figure 4

Examples of connections with a significant main effect of normalized pain score. Each panel presents an anatomical image indicating the source (above, blue, marked with s) and target region (below, yellow, marked with t) for each given connection. Each graph shows the relationship between the connectivity strength (β) and normalized pain score for each individual and group. Participants from the FM group are marked in red, the PVD group is marked in blue, and the HC group is marked in green, with a matching colour trendline for each group. Four connections are shown. Connections in the left column had a significant main effect of normalized pain score during the Expecting Pain period, while the right column is during the Experiencing Pain period. The upper panels feature connections where the trend in the FM group was different from the PVD and HC groups, while the lower panels show connections where the trend in the PVD group was different from the FM and HC groups.