A systematic review and meta-analysis of the prevalence of small fiber pathology in fibromyalgia: Implications for a new paradigm in fibromyalgia etiopathogenesis

Grayston, Rebecca; Czanner, Gabriela; Elhadd, Kareim; Göebel, Andreas; Frank, Bernhard; Üçeyler, Nurcan; Malik, Rayaz A.; Alam, Uazman

doi:10.1016/j.semarthrit.2018.08.003

Cited by 134 publications

(104 citation statements)

References 69 publications

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“…Another consideration may be that small fibre pathology occurs systemically in some people with chronic WAD. Reduced IENFD has been observed across a range of chronic pain conditions, including fibromyalgia (Grayston et al, 2019), central post‐stroke pain (Cavalier, Albrecht, Amory, Bernardini, & Argoff, 2016) and Gulf War Illness (Klein, Zirpoli, Downs, & Oaklander, 2018). Further, bilateral reductions in IENFD occur in people with unilateral complex regional pain syndrome (Rasmussen et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Small fibre pathology in chronic whiplash‐associated disorder: A cross‐sectional study

Farrell

Sterling

Irving-Rodgers

et al. 2020

European Journal of Pain

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Background Mechanisms underpinning ongoing symptoms in chronic whiplash associated‐disorder (WAD) are not well understood. People with chronic WAD can exhibit sensory dysfunction consistent with small nerve fibre pathology, including thermal hypoaesthesia and hyperalgesia. This study investigated small fibre structure and function in chronic WAD. Methods Twenty‐four people with chronic WAD (median [IQR] age 49 [15] years, 16 females) and 24 pain‐free controls (50 [17] years, 16 females) were recruited. Intraepidermal nerve fibre density (IENFD) and dermal innervation were assessed by skin biopsy. This was performed at (a) the lateral index finger on the primary side of pain and (b) superior to the lateral malleolus on the contralateral side. Quantitative sensory testing was performed over the hand. Results The WAD group exhibited lower IENFD at the finger (WAD: median [IQR] 4.5 [4.9] fibres/mm; control 7.3 [3.9]; p = .010), but not the ankle (WAD: mean [SD] 7.3 [3.7] fibres/mm; control 9.3 [3.8]; p = .09). Dermal innervation was lower in the WAD group at the finger (WAD: median [IQR] 3.7 [2.8] nerve bundles/mm2; controls: 4.9 [2.1]; p = .017) but not the ankle (WAD: median [IQR] 2.1 [1.9] nerve bundles/mm2; controls: 1.8 [1.8]; p = .70). In the WAD group, hand thermal and light touch detection were impaired, and heat pain thresholds were lowered (p ≤ .037). Conclusions Findings suggest small fibre structural and functional deficits in chronic WAD, implicating potential involvement of small fibre pathology. Significance Our study found decreased intraepidermal nerve fibre density, reduced dermal innervation, thermal hypoaesthesia and hypersensitivity in people with chronic WAD, suggestive of small fibre pathology. This observation of peripheral nervous system pathology in chronic whiplash provides novel insights on mechanisms underpinning symptoms and challenges commonly held beliefs regarding this condition.

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Section: Discussionmentioning

confidence: 99%

Small fibre pathology in chronic whiplash‐associated disorder: A cross‐sectional study

Farrell

Sterling

Irving-Rodgers

et al. 2020

European Journal of Pain

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“…Recently, Albrecht and colleagues have suggested a possible role for microglial activation and neuroinflammation [8]. Pathological changes in epidermal nerve fibres has also been implicated, with evidence for the association nearing 50% [9]. The role of oxidative stress, autoimmune markers, proteomics, genetics and a range of hormones have all been implicated with inconsistent results [10].…”

Section: Introductionmentioning

confidence: 99%

Determining the association between fibromyalgia, the gut microbiome and its biomarkers: A systematic review

Erdrich

Hawrelak

Myers

et al. 2020

BMC Musculoskelet Disord

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Background: The association between fibromyalgia and irritable bowel syndrome is well-established. Alterations in the composition and diversity of the gut microbiome in irritable bowel syndrome have been reported, however, this association is poorly understood in fibromyalgia. Our aim was to summarise the research reporting on the gastrointestinal microbiome and its biomarkers in people with fibromyalgia. Methods: A systematic review of published original research reporting on the gastrointestinal microbiota and its biomarkers in adults with a diagnosis of fibromyalgia was undertaken. Results: From 4771 studies, 11 met our inclusion criteria and were separated into four main groups: papers reporting Helicobacter pylori; other gut bacterial markers; metabolomics and other biomarkers, which included intestinal permeability and small intestinal bacterial overgrowth. Conclusion: The results suggest there is a paucity of quality research in this area, with indications that the gut microbiota may play a role in fibromyalgia within the emerging field of the gut-musculoskeletal axis. Further investigations into the relationship between the gut microbiota, gut dysfunction and fibromyalgia are warranted.

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“…Nervous system dysfunction is implicated and neurotransmitters are the targets of a number of drugs approved for fibromyalgia (7). Pathological changes in epidermal nerve fibres has recently been implicated, with evidence for the association nearing 50% (8). The role of oxidative stress, autoimmune markers, proteomics, genetics and a range of hormones have all been implicated with inconsistent results (9).…”

Section: Introductionmentioning

confidence: 99%

Determining the association between fibromyalgia, the gut microbiome and its biomarkers: A systematic review

Erdrich

Hawrelak

Myers

et al. 2020

Preprint

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Background The association between fibromyalgia and irritable bowel syndrome is well-established. Alterations in the composition and diversity of the gut microbiome in irritable bowel syndrome have been reported, however, this association is poorly understood in fibromyalgia. Our aim was to summarise the research reporting on the gastrointestinal microbiome and its biomarkers in people with fibromyalgia.Methods A systematic review of published original research reporting on the gastrointestinal microbiota and its biomarkers in adults with a diagnosis of fibromyalgia was undertaken.Results From 4771 studies, 11 met our inclusion criteria and were separated into four main groups: papers reporting Helicobacter pylori ; other gut bacterial markers; metabolomics and other biomarkers, which included intestinal permeability and small intestinal bacterial overgrowth.Conclusion The results suggest there is a paucity of quality research in this area, with indications that the gut microbiota may play a role in fibromyalgia within the emerging field of the gut-musculoskeletal axis. Further investigations into the relationship between the gut microbiota, gut dysfunction and fibromyalgia are warranted.

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A systematic review and meta-analysis of the prevalence of small fiber pathology in fibromyalgia: Implications for a new paradigm in fibromyalgia etiopathogenesis

Cited by 134 publications

References 69 publications

Small fibre pathology in chronic whiplash‐associated disorder: A cross‐sectional study

Small fibre pathology in chronic whiplash‐associated disorder: A cross‐sectional study

Determining the association between fibromyalgia, the gut microbiome and its biomarkers: A systematic review

Determining the association between fibromyalgia, the gut microbiome and its biomarkers: A systematic review

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