Abnormal immune system response in the brain of women with Fibromyalgia after experimental endotoxin challenge

Mueller, Christina; Jordan, Indonesia A.; Jones, Chloe; Lawson, Prentiss; Younger, Jarred

doi:10.1016/j.bbih.2023.100624

Cited by 4 publications

(3 citation statements)

References 66 publications

(77 reference statements)

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“…To assess the neural correlates of endotoxin effects on pain, few studies have implemented functional magnetic resonance imaging (fMRI) to measure blood oxygen level-dependent responses to painful stimuli and pain-associated signals. One recent study used magnetic resonance spectroscopy that allows analyzing biochemical changes in pain-related brain networks [ 59 ], reviewed in [ 60 ]. Complementing findings from studies using pain-provoking tests such as algometry or pinprick, spontaneous changes in pain sensitivity were assessed using self-report on pain-related symptoms, e.g., headaches, muscles, or joint pain.…”

Section: Inflammation and Painmentioning

confidence: 99%

“…To the best of our knowledge, only one study has used the model in a chronic pain population so far. This study in a small sample of women with fibromyalgia suggested that low-dose LPS may induce different changes in magnetic resonance spectroscopy-derived brain temperature and brain metabolites during systemic inflammation when compared to healthy controls [ 59 ]. One further study has investigated prior vulnerabilities [ 115 ] by injecting healthy obese individuals with LPS.…”

Section: Future Directionsmentioning

confidence: 99%

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How Can Experimental Endotoxemia Contribute to Our Understanding of Pain? A Narrative Review

Benson,

Karshikoff

2023

Neuroimmunomodulation

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Background: The immune system and the central nervous system exchange information continuously. This communication is a prerequisite for adaptive responses to physiological and psychological stressors. While the implicate relationship between inflammation and pain is increasingly recognized in clinical cohorts, the underlying mechanisms and the possibilities for pharmacological and psychological approaches aimed at neuro-immune communication in pain are not fully understood yet. This calls for preclinical models which build a bridge from clinical research to laboratory research. Summary: Experimental models of systemic inflammation (experimental endotoxemia) in humans have been increasingly recognized as an approach to study the direct and causal effects of inflammation on pain perception. This narrative review provides an overview of what experimental endotoxemia studies on pain have been able to clarify so far. We report that experimental endotoxemia results in a reproducible increase in pain sensitivity, particularly for pressure and visceral pain (deep pain), which is reflected in responses of brain areas involved in pain processing. Increased levels of blood inflammatory cytokines are required for this effect, but cytokine levels do not always predict pain intensity. We address sex-dependent differences in immunological responses to endotoxin, and discuss why these differences do not necessarily translate to differences in behavioral measures. We summarize psychological and cognitive factors that may moderate pain sensitization driven by immune activation. Key messages: Together, studying the immune-driven changes in pain during endotoxemia offers a deeper mechanistic understanding of the role of inflammation in chronic pain. Experimental endotoxemia models can specifically help to tease out inflammatory mechanisms underlying individual differences, vulnerabilities, and comorbid psychological problems in pain syndromes. The model offers the opportunity to test the efficacy of interventions, increasing their translational applicability for personalized medical approaches.

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Section: Inflammation and Painmentioning

confidence: 99%

Section: Future Directionsmentioning

confidence: 99%

How Can Experimental Endotoxemia Contribute to Our Understanding of Pain? A Narrative Review

Benson,

Karshikoff

2023

Neuroimmunomodulation

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“…However, this psychodynamic interpretation, at least in part, has recently been challenged [9]. Studies using spectroscopic magnetic resonance imaging (MRSI) have shown an abnormal thermal response after stimulation of immunity with endotoxin challenge in women with FM, suggesting a link between chronic widespread pain and the immune system [10]. In addition, a signature of genes encoding pro-inflammatory molecules produced by cells of the innate immune system, such as dendritic cells and neutrophils, has been identified in FM patients with associated depression [11].…”

Section: Introductionmentioning

confidence: 99%

Inflammation, Autoimmunity, and Infection in Fibromyalgia: A Narrative Review

Paroli,

Gioia,

Accapezzato

et al. 2024

IJMS

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Fibromyalgia (FM) is a chronic disease characterized by widespread musculoskeletal pain of unknown etiology. The condition is commonly associated with other symptoms, including fatigue, sleep disturbances, cognitive impairment, and depression. For this reason, FM is also referred to as FM syndrome. The nature of the pain is defined as nociplastic according to the latest international classification and is characterized by altered nervous sensitization both centrally and peripherally. Psychosocial conditions have traditionally been considered critical in the genesis of FM. However, recent studies in animal models and humans have provided new evidence in favor of an inflammatory and/or autoimmune pathogenesis. In support of this hypothesis are epidemiological data of an increased female prevalence, similar to that of autoimmune diseases, and the frequent association with immune-mediated inflammatory disorders. In addition, the observation of an increased incidence of this condition during long COVID revived the hypothesis of an infectious pathogenesis. This narrative review will, therefore, discuss the evidence supporting the immune-mediated pathogenesis of FM in light of the most current data available in the literature.

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Altered response to Toll-like receptor 4 activation in fibromyalgia: A low-dose, human experimental endotoxemia pilot study

Jones,

Parkitny,

Strath

et al. 2023

Brain, Behavior, & Immunity - Health

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Abnormal immune system response in the brain of women with Fibromyalgia after experimental endotoxin challenge

Cited by 4 publications

References 66 publications

How Can Experimental Endotoxemia Contribute to Our Understanding of Pain? A Narrative Review

How Can Experimental Endotoxemia Contribute to Our Understanding of Pain? A Narrative Review

Inflammation, Autoimmunity, and Infection in Fibromyalgia: A Narrative Review

Altered response to Toll-like receptor 4 activation in fibromyalgia: A low-dose, human experimental endotoxemia pilot study

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