Primary somatosensory cortex and periaqueductal gray functional connectivity as a marker of the dysfunction of the descending pain modulatory system in fibromyalgia

Abstract

Background: Resting-state functional connectivity (rs-FC) may aid in understanding the link between painmodulating brain regions and the descending pain modulatory system (DPMS) in fibromyalgia (FM). This study investigated whether the differences in rs-FC of the primary somatosensory cortex in responders and non-responders to the conditioned pain modulation test (CPM-test) are related to pain, sleep quality, central sensitization, and the impact of FM on quality of life. Methods: This cross-sectional study included 33 females with FM. rs-FC was assessed by functional magnetic resonance imaging. Change in the numerical pain scale during the CPM-test assessed the DPMS function. Subjects were classified either as non-responders (i.e., DPMS dysfunction, n = 13) or responders (n = 20) to CPM-test. A generalized linear model (GLM) and a receiver operating characteristic (ROC) curve analysis were performed to check the accuracy of the rs-FC to differentiate each group. Results: Non-responders showed a decreased rs-FC between the left somatosensory cortex (S1) and the periaqueductal gray (PAG) (P < 0.001). The GLM analysis revealed that the S1-PAG rs-FC in the left-brain hemisphere was positively correlated with a central sensitization symptom and negatively correlated with sleep quality and pain scores. ROC curve analysis showed that left S1-PAG rs-FC offers a sensitivity and specificity of 85% or higher (area under the curve, 0.78, 95% confidence interval, 0.63-0.94) to discriminate who does/does not respond to the CPM-test. Conclusions: These results support using the rs-FC patterns in the left S1-PAG as a marker for predicting CPM-test response, which may aid in treatment individualization in FM patients.

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

“…This reduced connectivity between these two structures was related to the severity of dysfunction in the descending pain modulatory system (DPMS). Also, the S1-PAG rs-FC in the left brain hemisphere was positively correlated with a central sensitization symptom and negatively correlated with sleep quality and pain scores [10]. Although we do not have a clear explanation for these findings as well as their relationship with the tDCS effect, we are aware that this is an exploratory analysis that agrees with previous research that individuals with fibromyalgia may exhibit increased connectivity patterns between different brain regions, including the insula and the S1 area [56,57].…”

“…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.…”

Repetitive Transcranial Magnetic Stimulation in Fibromyalgia: Exploring the Necessity of Neuronavigation for Targeting New Brain Regions

“…Advancements in understanding supraspinal pain processing mechanisms are being made through a range of neuroimaging techniques. These include structural methods like magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) [ 17 ], molecular approaches such as magnetic resonance spectroscopy (MRS) and positron emission tomography (PET) [ 18 ], and functional imaging modalities such as functional magnetic resonance imaging (fMRI) [ 19 , 20 ]. Through these methods, altered activations in numerous brain regions involved in pain processing have been revealed: Prefrontal Cortex (PFC): Involved in executive functions such as decision-making, attention, and emotional regulation.…”

Psycho-Neuroendocrinology in the Rehabilitation Field: Focus on the Complex Interplay between Stress and Pain

“…During signal transduction, various neurotransmitters are released, including glutamate, calcitonin gene-related peptide (CGRP), and substance P. From the dorsal horn, projection neurons decussate at the ventral commissure and ascend in the lateral spinothalamic tract to the ventral posterolateral nuclei of the thalamus [62,63]. Successively, information is transmitted to the somatosensory cortex and periaqueductal grey matter (PAG) [64]. However, other brain areas are involved in the transmission of nociceptive information, including the amygdala, hypothalamus, and nucleus accumbens through the spino-reticular and spino-mesencephalic tracts [65].…”

“…It receives an input from the PAG, and sorts diffuse bilateral projections to the dorsal horn, arriving at multiple levels. When a peripheral injury occurs, the interaction between neuronal and glial cells influences the development of pain hypersensitivity [64][65][66]. Glial cells, such as microglia, astrocytes, oligodendrocytes, and radial cells, have supportive and protective functions in both the central and peripheral nervous systems [67].…”