FMRI of spinal and supra‐spinal correlates of temporal pain summation in fibromyalgia patients

Abstract

Fibromyalgia syndrome (FM) is a debilitating chronic pain condition, which afflicts primarily females. Although the etiology of this illness is not completely understood, FM pain is thought to rely on enhanced pain sensitivity maintained by central mechanisms. One of these mechanisms is central pain amplification, which is characterized by altered temporal summation of second pain (TSSP). Here we use a TSSP paradigm and functional MRI (fMRI) of the spinal cord, brainstem, and brain to non-invasively examine the central nervous system contributions to TSSP in FM patients and normal controls (NC). Functional MRI of pain-free female adults (N = 15) and FM patients (N = 14) was conducted while brief, repetitive heat pain stimuli (0.33 Hz) were applied to the thenar eminence of the hand (C6 dermatome). The stimulus intensity was adjusted to each participant’s heat pain sensitivity to achieve moderate pain. Data were analyzed by means of a General Linear Model and region-of-interest analyses. All participants demonstrated significant pain summation in the TSSP condition. FM subjects, however, required significantly lower stimulus intensities than NC to achieve similar TSSP. fMRI analyses of perceptually equal TSSP identified similar brain activity in NC and FM subjects; however, multiple areas in the brainstem (RVM and PAG) and spinal cord (DH) exhibited greater activity in NC subjects. Finally, increased after-sensations and enhanced dorsal horn activity was demonstrated in FM patients. In conclusion, the spinal and brainstem BOLD responses to TSSP are different between NC and FM patients, which may indicate alterations to descending pain control mechanisms suggesting contributions of these mechanisms to central sensitization and pain of FM patients.

Painful After-Sensations in Fibromyalgia are Linked to Catastrophizing and Differences in Brain Response in the Medial Temporal Lobe

“…12 The present study found that PAS, which were prominent in subjects with FM, and more rare in control subjects, were associated with differences in MTL response (specifically, deactivation). Of note, MTL alterations have been previously reported in FM.…”

“…67 Importantly, a handful of studies have shown that PAS are more pronounced in FM patients than in control subjects. 12,62,70,72 Additionally, PAS appear to be more closely correlated to pain severity than other QST measures, including indices of temporal summation, 2,65,73 underlining their potential clinical relevance. Whereas PAS have been studied by several groups psychophysically, their associated brain activity has not been investigated.…”

Continuous Descending Modulation of the Spinal Cord Revealed by Functional MRI

“…Coordinated responses have also been demonstrated between brainstem and spinal cord regions in response to noxious heat stimuli, mechanical hyperalgesia, and stimulation to induce temporal summation of pain in healthy and fibromyalgia syndrome study groups. SEM analyses have further demonstrated brainstem and spinal cord networks in both healthy participants and people with spinal cord injuries [23, 29–33]. The coordinated responses to noxious stimuli in these studies provide evidence of responses to stimuli as well as descending modulation of the spinal cord.…”

Functional MRI of the Reserpine-Induced Putative Rat Model of Fibromyalgia Reveals Discriminatory Patterns of Functional Augmentation to Acute Nociceptive Stimuli

“…However we did not implement this experimental design because of the difficulty in applying matched perceived electrical stimulus to the anaesthetised rodent. An earlier study found evidence for altered descending pain control mechanisms in FM sufferers by measuring differential BOLD responses in the spine and brainstem relative to normal controls42. Our fMRI sequence did not capture these regions which may merit future investigation given the findings by Bosma et al .,42.…”

“…An earlier study found evidence for altered descending pain control mechanisms in FM sufferers by measuring differential BOLD responses in the spine and brainstem relative to normal controls42. Our fMRI sequence did not capture these regions which may merit future investigation given the findings by Bosma et al .,42. There is evidence that FM patients also exhibit altered temporal BOLD response profiles43 and examination of this property in the RIM model would represent an interesting extension of this work, though beyond the scope of the current investigation.…”