Evaluation of Cytokine Levels in Fibromyalgia Syndrome Patients and its Relationship to the Severity of Chronic Pain<sup>†</sup>

Malhotra, Dipti; Saxena, Arushi; Dar, Sajad Ahmad; Kumar, Vivek; Nasare, Namita; Tripathi, Ashok Kr.; Banerjee, Basu Dev

doi:10.3109/10582452.2012.704141

Cited by 24 publications

(23 citation statements)

References 23 publications

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“…These studies presented different chronic pain charts, so this finding may be related to chronic musculoskeletal pain of different origins. Another relationship found in the cytokine and chronic pain ratio was the decrease of anti-inflammatory cytokines in patients with chronic pain when compared to controls 13,14,17,19 . This information may facilitate the modification of pain perception, since IL-10, for example, plays an important role as a pain perception blocker 23 .…”

Section: Discussionmentioning

confidence: 97%

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Systemic alterations in plasma biomarkers levels in patients with chronic pain

Vendrúsculo-Fangel

Fangel

Marqueti

2019

Brazilian Journal of Pain

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BACKGROUND AND OBJECTIVES: To analyze the scientific evidence on the changes in plasma levels of interleukins, nitric oxide, extracellular matrix metalloproteinases, bradykinins, and cortisol in patients with chronic pain. CONTENTS: The studies were identified by searching the following electronic databases: Pubmed/Medline, Scopus, LILACS, and Web of Science, published from June of 2016 to December of 2016. The selected articles were presented in a flow chart based on their identification, selection, eligibility and inclusion and exclusion criteria. The content of the articles included in the study was analyzed to identify the biomarkers present in patients with chronic pain. Thirteen articles that addressed the plasma biomarkers levels in humans with chronic pain were selected. Most of the articles presented the cytokines levels, followed by cortisol. Only one article mentioned the nitric oxide, and none mentioned what plasma levels of extracellular matrix metalloproteinases and bradykinins were identified. CONCLUSION: Changes were observed in inflammatory and anti-inflammatory cytokine plasma levels, and that cortisol is related to anxiety and depression symptoms in patients with chronic pain. However, it was not possible to identify the changes in plasma levels of nitric oxide, bradykinin, and extracellular matrix metalloproteinases due to the absence of scientific evidence.

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Section: Discussionmentioning

confidence: 97%

“…12 Bäckryd et al 20 Neuropathic chronic pain (14) Healthy control (17) Cytokines (IL-1, IL-6, IL-8, and GM--CSF).…”

Section: Inclusion and Exclusion Criteriamentioning

confidence: 99%

Systemic alterations in plasma biomarkers levels in patients with chronic pain

Vendrúsculo-Fangel

Fangel

Marqueti

2019

Brazilian Journal of Pain

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“…Since stressful stimuli increase plasma levels of pro-inflammatory cytokines [45], including MCP-1 [19], they have been suggested to contribute to chronic widespread pain syndromes [46; 60]. Furthermore, patients affected by chronic widespread muscle pain also exhibit increased levels of MCP-1 [19; 41; 67].…”

Section: Discussionmentioning

confidence: 99%

Role for monocyte chemoattractant protein-1 in the induction of chronic muscle pain in the rat

Álvarez

Green

Levine

2014

Pain

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Summary Whether MCP-1 contributes to chronic musculoskeletal pain is unknown. We provide evidence that MCP-1 induces acute muscle hyperalgesia and a state of chronic nociceptive sensitization. While raised levels of monocyte chemoattractant protein 1 (MCP-1) have been observed in patients with chronic muscle pain, direct evidence for its role as an algogen in skeletal muscle is still lacking. In the rat, MCP-1 induces a dose-dependent mechanical hyperalgesia lasting for up to 6 weeks. Following recovery, rats exhibited a markedly prolonged hyperalgesia to an intramuscular injection of prostaglandin E2, hyperalgesic priming. Intrathecal pre-treatment with isolectin B4 (IB4)-saporin, which selectively destroys IB4-positive (IB4+) nociceptors, markedly decreased MCP-1 induced hyperalgesia and prevented the subsequent development of priming. To evaluate the involvement of MCP-1 in stress-induced chronic pain we administered, intrathecally (i.t.), antisense (AS) or mismatch (MM) oligodeoxynucleotides directed against CCR2 (the canonical receptor for MCP-1) mRNA, during the exposure to water avoidance stress, a model of stress-induced persistent muscle pain. The AS treatment attenuated this hyperalgesia, whereas IB4-saporin abolished water avoidance stress-induced muscle hyperalgesia and prevented stress-induced hyperalgesic priming. These results indicate that MCP-1 induces persistent muscle hyperalgesia and a state of latent chronic sensitization to other algogens, by action on its cognate receptor on IB4+ nociceptors. Since MCP-1 also contributes to stress-induced widespread chronic muscle pain, it should be considered as a player in chronic musculoskeletal pain syndromes.

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“…However, reports about the effect of adrenergic agonists on systemic LPS-induced TNFα and IL-6 production have been contradictory (70–72). Thus, while patients affected by a chronic widespread pain syndrome exhibit sympathoadrenal dysfunction (73), increased release of TNFα/IL-6 (74, 75) and aggravation of their symptoms after stress (9, 11–14), their muscle pain symptoms cannot be explained solely by changes on TNFα/IL-6 plasma levels.…”

Section: Discussionmentioning

confidence: 99%

Stress in the Adult Rat Exacerbates Muscle Pain Induced by Early-Life Stress

Álvarez

Green

Levine

2013

Biological Psychiatry

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Background Early-life stress and exposure to stressful stimuli play a major role in the development of chronic widespread pain in adults. However, how they interact in chronic pain syndromes remains unclear. Methods Dams and neonatal litters were submitted to a restriction of nesting material (neonatal limited bedding, NLB) for one week. As adults, these rats were exposed to a painless sound stress protocol. The involvement of sympathoadrenal catecholamines, interleukin 6 (IL-6) and tumor necrosis alpha (TNFα) in nociception, was evaluated through of behavioral and ELISA assays, surgical interventions and intrathecal antisense treatments. Results Adult NLB rats exhibited mild muscle hyperalgesia, which was markedly aggravated by sound stress (peaking 15 days after exposure). Adrenal medullectomy did not modify hyperalgesia in NLB rats but prevented its aggravation by sound stress. Sustained administration of epinephrine to NLB rats mimicked sound stress effect. Intrathecal treatment with antisense directed to IL-6-receptor subunit gp130, but not to TNFα type 1 receptor (TNFR1), inhibited hyperalgesia in NLB rats. However, antisense against either gp130 or TNFR1 inhibited sound stress-induced enhancement of hyperalgesia. Compared to control rats, NLB rats exhibit increased plasma levels of IL-6 but decreased levels of TNFα, whereas sound stress increases IL-6 plasma levels in control but not in NLB rats. Conclusions Early-life stress induces a persistent elevation of IL-6, hyperalgesia and susceptibility to chronic muscle pain, which is unveiled by exposure to stress in adults. This probably depends on an interaction between adrenal catecholamines and pro-inflammatory cytokines acting at muscle nociceptor level.

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Evaluation of Cytokine Levels in Fibromyalgia Syndrome Patients and its Relationship to the Severity of Chronic Pain^†

Cited by 24 publications

References 23 publications

Systemic alterations in plasma biomarkers levels in patients with chronic pain

Systemic alterations in plasma biomarkers levels in patients with chronic pain

Role for monocyte chemoattractant protein-1 in the induction of chronic muscle pain in the rat

Stress in the Adult Rat Exacerbates Muscle Pain Induced by Early-Life Stress

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Evaluation of Cytokine Levels in Fibromyalgia Syndrome Patients and its Relationship to the Severity of Chronic Pain†

Cited by 24 publications

References 23 publications

Systemic alterations in plasma biomarkers levels in patients with chronic pain

Systemic alterations in plasma biomarkers levels in patients with chronic pain

Role for monocyte chemoattractant protein-1 in the induction of chronic muscle pain in the rat

Stress in the Adult Rat Exacerbates Muscle Pain Induced by Early-Life Stress

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Evaluation of Cytokine Levels in Fibromyalgia Syndrome Patients and its Relationship to the Severity of Chronic Pain^†