Hyper-connectivity between the left motor cortex and prefrontal cortex is associated with the severity of dysfunction of the descending pain modulatory system in fibromyalgia

Abstract

Introduction The association between descending pain modulatory system (DPMS) dysfunction and fibromyalgia has been previously described, but more studies are required on its relationship with aberrant functional connectivity (FC) between the motor and prefrontal cortices. Objectives The objective of this cross-sectional observational study was to compare the intra- and interhemispheric FC between the bilateral motor and prefrontal cortices in women with fibromyalgia, comparing responders and nonresponders to the conditioned pain modulation (CPM) test. Methods A cross-sectional sample of 37 women (23 responders and 14 nonresponders to the CPM test) with fibromyalgia diagnosed according to the American College of Rheumatology criteria underwent a standardized clinical assessment and an FC analysis using functional near-infrared spectroscopy. DPMS function was inferred through responses to the CPM test, which were induced by hand immersion in cold water (0–1°C). A multivariate analysis of covariance for main effects between responders and nonresponders was conducted using the diagnosis of multiple psychiatric disorders and the use of opioid and nonopioid analgesics as covariates. In addition, we analyzed the interaction between the CPM test response and the presence of multiple psychiatric diagnoses. Results Nonresponders showed increased FC between the left motor cortex (lMC) and the left prefrontal cortex (lPFC) (t = −2.476, p = 0.01) and right prefrontal cortex (rPFC) (t = −2.363, p = 0.02), even when both were considered as covariates in the regression analysis (lMC–lPFC: β = −0.127, t = −2.425, p = 0.021; lMC–rPFC: β = −0.122, t = −2.222, p = 0.033). Regarding main effects, a significant difference was only observed for lMC–lPFC (p = 0.035). A significant interaction was observed between the psychiatric disorders and nonresponse to the CPM test in lMC−lPFC (β = −0.222, t = −2.275, p = 0.03) and lMC−rPFC (β = −0.211, t = −2.2, p = 0.035). Additionally, a significant interaction was observed between the CPM test and FC in these two region-of-interest combinations, despite the psychiatric diagnoses (lMC−lPFC: β = −0.516, t = −2.447, p = 0.02; lMC−rPFC: β = −0.582, t = −2.805, p = 0.008). Conclusions Higher FC between the lMC and the bilateral PFC may be a neural marker of DPMS dysfunction in women with fibromyalgia, although its interplay with psychiatric diagnoses also seems to influence this association.

Pain and the emotional brain: pain-related cortical processes are better reflected by affective evaluation than by cognitive evaluation

“…Consequently, the decreased connectivity for prolonged pain stimulation periods may not generalise to other experimental pain conditions. Indeed, unlike our findings with brain-wide disconnection in response to painful stimulation, other studies that investigate pain-related connectivity in response to brief pain have reported increased connectivity during pain perception 38 , 39 .…”

High-beta oscillations at EEG resting state and hyperconnectivity of pain circuitry in fibromyalgia: an exploratory cross-sectional study

“…The SI is responsible for encoding sensory aspects of pain, whereas the ACC is involved in affective processing. According to an earlier study, when patients with central sensitization are exposed to sensory stimuli, there is more neuronal activity in areas that process sensory information ( de Oliveira Franco et al, 2022b ). Significant structural, chemical, and functional changes have also been observed in pain-related brain areas, such as the cingulate and somatosensory cortices ( Nir et al, 2008 ; Harte et al, 2018 ).…”

Modulation of Neural Networks and Symptom Correlated in Fibromyalgia: A Randomized Double-blind Factorial Explanatory Clinical Trial of Home-Based Transcranial Direct Current Stimulation

“…Discriminatory analysis indicated a significant difference in group interconnectivity patterns [9]. Even though there is evidence that dysfunctional processing in FM is caused by dysfunctional connectivity and dysfunction of the DPMS [7,10], there is not much evidence about how treatment affects these neural markers. Thus, it is crucial to investigate the effect of treatments on these neural markers associated with the severity of pain symptoms, which can help develop effective treatments for pain management and personalized treatment.…”

“…FC is the degree to which activity between a pair of brain regions covaries or correlates over time. In FM, the descending pain modulatory system (DPMS) does not work as well when there is more functional connectivity (FC) between pain processing areas like the left motor cortex (MC) and the left prefrontal cortex (PFC), as well as between the left MC and the right PFC [7]. Another study in FM found an increased delta value of FC in response to acute pain between the PFC and MC in genotypes BDNF Val/Met compared to Val/Val [8].…”