Tag: nociplastic pain

Altered Pain Perception and Modulation in Individuals With Post-COVID-Condition: Insights From Quantitative Sensory Testing

Abstract:

Introduction: Chronic pain is a significant and debilitating symptom observed in individuals with post-COVID condition (PCC), yet the underlying mechanisms remain poorly understood. This study aimed to investigate whether changes in psychophysical indicators of myofascial pain perception and modulation are present in individuals with PCC compared to symptom-free healthy controls (HC), and whether these changes correlate with the severity of clinical symptoms.

Methods: The study involved 84 individuals with PCC and 50 HC, assessing pain detection and tolerance thresholds (PDT and PTT), spatial and temporal summation of pain (SSP and TSP), and conditioned pain modulation (CPM) using phasic cuff pressure on the legs.

Results: Results indicated that individuals with PCC exhibited lower PDT and PPT (PDT: d = -0.557, p = 0.0022; PTT: d = -0.575, p = 0.0016), increased TSP (d = 0.424, p = 0.02) and decreased SSPPTT (d = -0.532, p = 0.0038) compared to HC CPM effects (CPMPDT: p = 0.058; CPMPTT: p = 0.43) did not differ significantly between groups but post hoc analysis revealed a significantly higher proportion of inhibitory responders among HC. Subgroup analyses highlighted that these effects were particularly pronounced in participants that reported chronic pain among their PCC symptoms, as well as those with more severe PCC symptomatology.

Conclusion: The findings suggest that individuals with PCC demonstrate altered myofascial pain perception, indicative of central sensitization. These results underscore the need for further research into targeted therapeutic strategies for managing chronic pain in PCC.

Significance statement: Individuals with post-COVID condition (PCC) often experience persistent pain. Using quantitative sensory testing of deep tissue pain, we found that individuals with PCC had lower pain detection and tolerance thresholds, stronger spatial and temporal summation, and a higher proportion of facilitatory conditioned pain modulation compared to healthy controls. This pattern is consistent with nociplastic pain, suggesting altered central pain processing in PCC. Understanding these mechanisms is essential for developing targeted treatments of chronic pain in this growing patient population.

Source: Lange H, Reichert J, Vock S, Hermes M, Beiner E, Eich W, Friederich HC, Treede RD, Tesarz J. Altered Pain Perception and Modulation in Individuals With Post-COVID-Condition: Insights From Quantitative Sensory Testing. Eur J Pain. 2026 Feb;30(2):e70203. doi: 10.1002/ejp.70203. PMID: 41699921. https://pubmed.ncbi.nlm.nih.gov/41699921/

Fatigue, interoplastic and nociplastic distress in myalgic encephalomyelitis/chronic fatigue syndrome, Gulf War Illness, and chronic idiopathic fatigue

Abstract:

Introduction: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Gulf War Illness (GWI) have similar profiles of pain (nociception), visceral interoception, and tenderness (central sensitization) that may be due to dysfunction of midbrain and medulla descending antinociceptive and antiinteroceptive mechanisms. If so, then dolorimetry, a proxy for tenderness, may be correlated with subjective symptoms. The relationship with fatigue was assessed in Chronic Idiopathic Fatigue (CIF).

Methods: Cohorts of ME/CFS, GWI, and sedentary control subjects completed questionnaires and had dolorimetry. Spearman correlations were calculated between central sensitization (dolorimetry), fatigue (Chalder Fatigue), pain (McGill Pain), interoception (Chronic Multisymptom Inventory), disability (SF36), psychological constructs, and other symptoms. Females were more tender than males and were thus analyzed separately.

Results: GWI and ME/CFS groups were more tender than controls for females (p < 0.0045) and males (p < 10-6). Receiver operating characteristics area under the curve for female ME/CFS (0.730) and GWI (0.792) and male ME/CFS (0.816) and GWI (0.831) were not optimal for diagnostic purposes. Pain and interoception were highly correlated. Dolorimetry correlated better with pain (Spearman R = -0.574 to -0.629) than interoception (R = -0.417 to -0.545) questionnaires. Dolorimetry correlated weakly with fatigue and disability (|R| < 0.42). CIF was defined by receiver operating characteristics with elevated fatigue, postexertional malaise, and reduced vitality. CIF had intermediate tenderness.

Discussion: The outcomes generate several hypotheses about ME/CFS and GWI pathophysiology. Disease pathologies may involve injury to midbrain and medulla regulatory pathways causing central sensitization with the loss of descending antiinteroceptive and antinociceptive inhibitory mechanisms and increased perceptions of widespread visceral complaints and pain. The diseases can be re-conceptualized as chronic disabling fatigue with heightened interoceptive and nociceptive symptoms. Variations in antiinteroceptive control may provoke unpredictable shifts in symptom spectrum and severity that contribute to exertional exhaustion and symptom exacerbation. Subjective criteria were found to define CIF prospectively.

Source: Chen E, Rudder T, Nwankwere C, Baraniuk JN. Fatigue, interoplastic and nociplastic distress in myalgic encephalomyelitis/chronic fatigue syndrome, Gulf War Illness, and chronic idiopathic fatigue. Front Neurosci. 2025 Aug 25;19:1530652. doi: 10.3389/fnins.2025.1530652. PMID: 40927423; PMCID: PMC12415031. https://pmc.ncbi.nlm.nih.gov/articles/PMC12415031/ (Full text)

Is fibromyalgia an autoimmune disorder?

Highlights:

  • Certain aspects of FM are still controversial, including pathophysiology, which remain a subject of debate
  • FM shares many clinical features, sometimes designing overlapping diseases, with other conditions, including, chronic fatigue syndrome (CFS), sick building syndrome (SBS), post-COVID syndrome, and many others
  • Anti-GPCR (anti- G protein-coupled receptor antibodies), autoantibodies directed against the autonomic nervous system receptors, have been detected in the serum of patients with FM, and their titers correlated with clinical symptoms
  • Fibromyalgia belongs to nociplastic pain which means that the central nervous system is the driving force behind this pain mechanism, and the key phenotypic features include widespread pain, fatigue, and sleep, memory, and mood disturbances

Abstract:

Fibromyalgia (FM) is a multifactorial syndrome which includes not only widespread pain and stiffness, now recognized as major symptoms, but also numerous other somatic, emotional, and neuropsychic manifestation. The lack of specific validated biological and instrumental biomarkers has made FM a condition of unexplained medical significance, and its pathophysiology remains controversial and subject to debate. The current hypothesis regarding the pathogenesis of FM proposes that its development is influenced by various mechanism, including genetic predisposition, stressful life events, inflammatory processes, and cognitive-emotional factors. However, despite the extensive research conducted to date, the available data do not provide a clear understanding of the pathogenesis of FM.
In this article, we report the opposing viewpoints of two leading experts who debate the question of whether FM is an autoimmune disease, based on scientific data regarding this condition. Both perspectives are discussed and the latest evidence on the pathophysiology of FM is reported to provide a comprehensive understanding of this complex syndrome.
Source: Clauw D, Sarzi-Puttini P, Pellegrino G, Shoenfeld Y. Is fibromyalgia an autoimmune disorder? Autoimmun Rev. 2024 Jan;23(1):103424. doi: 10.1016/j.autrev.2023.103424. Epub 2023 Aug 25. PMID: 37634681. https://www.sciencedirect.com/science/article/pii/S1568997223001581 (Full text)