Mapping of predictors of the disengagement of the descending inhibitory pain modulation system in fibromyalgia: an exploratory study

Abstract

Background: The main symptoms of fibromyalgia comprise diffuse pain, disability, depressive symptoms, catastrophizing, sleep disruption and fatigue, associated with dysfunction of the descending pain-modulating system (DPMS). Objectives: We aimed to identify patterns of main symptoms of fibromyalgia and neuroplasticity biomarkers (i.e. brain-derived neurotrophic factor (BDNF) and S100B protein) in non-responders to the conditioned pain modulation task (CPM-task) induced by immersion of hand in cold water (0–1°C). Furthermore, we evaluated if these patterns predict responsiveness to CPM-task. Methods: This cross-sectional study included 117 women with fibromyalgia (( n = 60) non-responders and ( n = 57) responders), with age ranging from 30 to 65 years old. We analysed changes in numerical pain scale (NPS-10) during the CPM-task using a standardized protocol. Results: A hierarchical multivariate logistic regression analysis was used to construct a propensity score-adjusted index to identify non-responders compared to responders to CPM-task. The following variables were retained in the models: analgesic use four or more times per week, heat pain threshold (HPT), poor sleep quality, pain catastrophizing, serum levels of BDNF, number of psychiatric diagnoses and the impact of symptoms of fibromyalgia on quality of life. Receiver operator characteristics (ROC) analysis showed non-responders can be discriminated from responders by a composite index of more frequent symptoms of fibromyalgia and neuroplasticity markers (area under the curve (AUC) = 0.83, sensitivity = 100% and specificity = 98%). Conclusion: Patterns of fibromyalgia symptoms and neuroplasticity markers may be helpful to predict responsiveness to the CPM-task which might help personalize treatment and thereby contribute to the care of patients with fibromyalgia.

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

“…Thus, these areas’ hyper-connectivity suggests that the FC may be a marker of cortical network reorganization, and it highlights that this cortical restructuring is associated with DPMS dysfunction. These functional changes may also be processes underpinning central sensitization’s pathophysiology, integrating cortical brain networks’ deterioration with the corticospinal pain pathways [60]. Consistent with our findings of increased FC in DPMS dysfunction, earlier fMRI studies found that in patients with chronic pain, including chronic low back pain and fibromyalgia, the increased FC between the insula cortex and default mode network, including the medial PFC, is correlated with pain perception intensity [11, 39, 42].…”

“…We conducted this study to test whether FC by fNIRS in fibromyalgia patients might constitute a biomarker of the DPMS dysfunction assessed by the CPM-test, evaluated according to changes in the Numerical Pain Scale (NPS) (0-10 points) during the immersion of the dominant hand in cold water [60]. Therefore, we have compared the FC of bilateral MC and PFC between groups of CPM-test responders and nonresponders in female fibromyalgia patients.…”

“…In contrast, the MC is a significant top-down inhibitory effector, representing a promising area for neuromodulatory intervention [21, 69]. The function of DPMS in fibromyalgia may be assessed by the conditioned pain modulation test (CPM-test) [10], in which higher dysfunction levels correlate with greater fibromyalgia symptom severity and functional disability [60].…”

Association between descending pain modulatory system and cognitive impairment in fibromyalgia: A cross-sectional exploratory study

“…Third, the difference between the NPS 0-10 at the start of the test (T0) and the pain score on the NPS (0-10) during the cold-water immersion (QST + CPM-test) at the temperature set at 6/10 during T1 was used to determine the CPM-test score. Responders would have values lower than zero whereas non-responders would have a difference in the count on NPS (T1 T0) equal to zero or higher (Botelho et al, 2016;Soldatelli et al, 2021). (f) Pain pressure threshold (PPT): To conduct the test, we employed an electronic algometer from J-Tech Medical Industries in Midvale, Utah, United States.…”

“…In several musculoskeletal chronic pain diseases, such as myofascial pain syndrome, FM, and osteoarthritis, the intensity of descending pain inhibitory system (DPIS) dysfunction is connected to pain severity ( Botelho et al, 2016 ; Caumo et al, 2016 ). Additionally, serum brain-derived neurotrophic factor (BDNF) levels have a positive correlation with the degree of DPMS dysfunction ( Soldatelli et al, 2021 ). According to Ong et al (2019) , this neurotrophic factor is highly expressed in the PFC in chronic pain and is a crucial marker of neuroplasticity linked to structural changes in various cortical regions responsible for learning, memory, fear, and emotional responses (such as the hippocampus and amygdala) ( Mazza et al, 2018 ).…”