Inflammatory Blood Signature Related to Common Psychological Comorbidity in Chronic Pain

Karshikoff, Bianka; Wåhlén, Karin; Åström, Jenny; Lekander, Mats; Holmström, Linda; Wicksell, Rikard K.

doi:10.3390/biomedicines11030713

Cited by 4 publications

(3 citation statements)

References 88 publications

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“…Plasma proteomic studies of FM patients have found protein patterns correlating with psychological distress aspects ( 35 , 125 ). Also, studies using targeted panels of proteins have reported significant corelations between plasma protein patterns and anxiety and depression in a mixed group of chronic pain patients ( 145 ). We are not aware of studies investigating the relationships with health.…”

Section: Discussionmentioning

confidence: 99%

Pain and the biochemistry of fibromyalgia: patterns of peripheral cytokines and chemokines contribute to the differentiation between fibromyalgia and controls and are associated with pain, fat infiltration and content

Gerdle,

Dahlqvist Leinhard,

Lund

et al. 2024

Front. Pain Res.

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ObjectivesThis explorative study analyses interrelationships between peripheral compounds in saliva, plasma, and muscles together with body composition variables in healthy subjects and in fibromyalgia patients (FM). There is a need to better understand the extent cytokines and chemokines are associated with body composition and which cytokines and chemokines differentiate FM from healthy controls.MethodsHere, 32 female FM patients and 30 age-matched female healthy controls underwent a clinical examination that included blood sample, saliva samples, and pain threshold tests. In addition, the subjects completed a health questionnaire. From these blood and saliva samples, a panel of 68 mainly cytokines and chemokines were determined. Microdialysis of trapezius and erector spinae muscles, phosphorus-31 magnetic resonance spectroscopy of erector spinae muscle, and whole-body magnetic resonance imaging for determination of body composition (BC)—i.e., muscle volume, fat content and infiltration—were also performed.ResultsAfter standardizing BC measurements to remove the confounding effect of Body Mass Index, fat infiltration and content are generally increased, and fat-free muscle volume is decreased in FM. Mainly saliva proteins differentiated FM from controls. When including all investigated compounds and BC variables, fat infiltration and content variables were most important, followed by muscle compounds and cytokines and chemokines from saliva and plasma. Various plasma proteins correlated positively with pain intensity in FM and negatively with pain thresholds in all subjects taken together. A mix of increased plasma cytokines and chemokines correlated with an index covering fat infiltration and content in different tissues. When muscle compounds were included in the analysis, several of these were identified as the most important regressors, although many plasma and saliva proteins remained significant.DiscussionPeripheral factors were important for group differentiation between FM and controls. In saliva (but not plasma), cytokines and chemokines were significantly associated with group membership as saliva compounds were increased in FM. The importance of peripheral factors for group differentiation increased when muscle compounds and body composition variables were also included. Plasma proteins were important for pain intensity and sensitivity. Cytokines and chemokines mainly from plasma were also significantly and positively associated with a fat infiltration and content index.ConclusionOur findings of associations between cytokines and chemokines and fat infiltration and content in different tissues confirm that inflammation and immune factors are secreted from adipose tissue. FM is clearly characterized by complex interactions between peripheral tissues and the peripheral and central nervous systems, including nociceptive, immune, and neuroendocrine processes.

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Section: Discussionmentioning

confidence: 99%

Pain and the biochemistry of fibromyalgia: patterns of peripheral cytokines and chemokines contribute to the differentiation between fibromyalgia and controls and are associated with pain, fat infiltration and content

Gerdle,

Dahlqvist Leinhard,

Lund

et al. 2024

Front. Pain Res.

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“…On the other hand, higher IL-8 levels were related to less widespread pain in chronic pelvic pain [ 48 ] and fewer depressive symptoms [ 49 ] in treatment-resistant depression in women but not in men. Moreover, in exploratory proteomics analyses, distinct networks of blood markers appear related to defined aspects of the disorder, such as pain intensity, pain sensitivity, or psychological comorbidity [ 50 , 51 ].…”

Section: Inflammation and Painmentioning

confidence: 99%

“…Pain comorbidity could represent a double-hit challenge for the CNS, as discussed above. Moreover, some studies suggest that patients experiencing both pain and mood disturbances may in fact show unique inflammatory characteristics [ 50 , 51 , 87 ]. For example, treatment-resistant depressed patients who experience pain comorbidity have higher blood IL-6 and granulocyte-macrophage colony-stimulating factor levels compared to patients without pain [ 88 ].…”

Section: Mood and Cognition Interact With Inflammation And Painmentioning

confidence: 99%

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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Methods and clinical biomarker discovery for targeted proteomics using Olink technology

Wang,

Zhao,

Zeng

et al. 2024

Proteomics Clinical Apps

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PurposeThis paper is to offer insights for designing research utilizing Olink technology to identify biomarkers and potential therapeutic targets for disease treatment.Experimental DesignWe discusses the application of Olink technology in oncology, cardiovascular, respiratory and immune‐related diseases, and Outlines the advantages and limitations of Olink technology.ResultsOlink technology simplifies the search for therapeutic targets, advances proteomics research, reveals the pathogenesis of diseases, and ultimately helps patients develop precision treatments.ConclusionsAlthough proteomics technology has been rapidly developed in recent years, each method has its own disadvantages, so in the future research, more methods should be selected for combined application to verify each other.

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Inflammatory Blood Signature Related to Common Psychological Comorbidity in Chronic Pain

Cited by 4 publications

References 88 publications

Pain and the biochemistry of fibromyalgia: patterns of peripheral cytokines and chemokines contribute to the differentiation between fibromyalgia and controls and are associated with pain, fat infiltration and content

Pain and the biochemistry of fibromyalgia: patterns of peripheral cytokines and chemokines contribute to the differentiation between fibromyalgia and controls and are associated with pain, fat infiltration and content

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

Methods and clinical biomarker discovery for targeted proteomics using Olink technology

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