Increased cutaneous miR-let-7d expression correlates with small nerve fiber pathology in patients with fibromyalgia syndrome

Leinders, Mathias; Doppler, Kathrin; Klein, Thomas; Deckart, Maximiliane; Rittner, Heike L.; Sommer, Claudia; Üçeyler, Nurcan

doi:10.1097/j.pain.0000000000000668

Cited by 60 publications

(64 citation statements)

References 85 publications

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“…Absent LEPs and SSR may also underlie a small fibers involvement with clinical appearance of neuropathic features, as assessed by DN4 test. As far as evidence is increasing in respect to central and peripheral nervous involvement in FM [53], the present results could point out the opportunity to submit such patients to the neurophysiological assessment of nociceptive and vegetative systems, possibly completed by skin biopsy.…”

Section: Discussionmentioning

confidence: 83%

Pain Processing and Vegetative Dysfunction in Fibromyalgia: A Study by Sympathetic Skin Response and Laser Evoked Potentials

Tommaso

Ricci

Libro

et al. 2017

Pain Research and Treatment

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Background A dysfunction of pain processing at central and peripheral levels was reported in fibromyalgia (FM). We aimed to correlate laser evoked potentials (LEPs), Sympathetic Skin Response (SSR), and clinical features in FM patients. Methods Fifty FM patients and 30 age-matched controls underwent LEPs and SSR by the right hand and foot. The clinical evaluation included FM disability (FIQ) and severity scores (WPI), anxiety (SAS) and depression (SDS) scales, and questionnaires for neuropathic pain (DN4). Results The LEP P2 latency and amplitude and the SSR latency were increased in FM group. This latter feature was more evident in anxious patients. The LEPs habituation was reduced in FM patients and correlated to pain severity scores. In a significant number of patients (32%) with higher DN4 and FIQ scores, SSR or LEP responses were absent. Conclusions LEPs and SSR might contribute to clarifying the peripheral and central nervous system involvement in FM patients.

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Section: Discussionmentioning

confidence: 83%

Pain Processing and Vegetative Dysfunction in Fibromyalgia: A Study by Sympathetic Skin Response and Laser Evoked Potentials

Tommaso

Ricci

Libro

et al. 2017

Pain Research and Treatment

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“…In recent studies, small nerve fiber pathology was found in subgroups of patients with fibromyalgia syndrome (FMS) . Applying corneal confocal microscopy (CCM), corneal denervation was also reported in FMS patients …”

Section: Introductionmentioning

confidence: 99%

Reduced association between dendritic cells and corneal sub‐basal nerve fibers in patients with fibromyalgia syndrome

Klitsch

Evdokimov

Frank

et al. 2020

J Peripheral Nervous Sys

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In our study, we aimed at investigating corneal langerhans cells (LC) in patients with fibromyalgia syndrome (FMS) and small fiber neuropathy (SFN) as potential contributors to corneal small fiber pathology. We enrolled women with FMS (n = 134) and SFN (n = 41) who underwent neurological examination, neurophysiology, prostaglandin analysis in tear fluid, and corneal confocal microscopy (CCM). Data were compared with those of 60 age‐matched female controls. After screening for dry eye disease, corneal LC were counted and sub‐classified as dendritic (dLC) and non‐dendritic (ndLC) cells with or without nerve fiber association. We further analyzed corneal nerve fiber density (CNFD), length (CNFL), and branch density (CNBD). Neurological examination indicated deficits of small fiber function in patients with SFN. Nerve conduction studies were normal in all participants. Dry eye disease was more prevalent in FMS (17%) and SFN (28%) patients than in controls (5%). Tear fluid prostaglandin levels did not differ between FMS patients and controls. While corneal LC density in FMS and SFN patients was not different from controls, there were fewer dLC in association with nerve fibers in FMS and SFN patients than in controls (P < .01 each). Compared to controls, CNFL was lower in FMS and SFN patients (P < .05 each), CNFD was lower only in FMS patients (P < .05), and CNBD was lower only in SFN patients (P < .001). There was no difference in any CCM parameter between patients with and without dry eyes. Our data indicate changes in corneal innervation and LC distribution in FMS and SFN, potentially based on altered LC signaling.

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“…Further, studies have found heat related hypoesthesia and hypoalgesia in patients with lateral epicondylalgia 34 increased thermal detection thresholds, and skin biopsies confirmed a loss of small thin cutaneous never fibers. Leinders et al, 2016 37 recently found that several systemic mirco-RNAs (miR), specifically miR-103, miR-151, and miR-let-7d, were downregulated in patients with fibromyalgia whereas cutaneous miR-let-7d was elevated in patients with reduced small nerve fiber density. miR-let7d has previously been found to be associated with chronic pain in patients with complex regional pain syndrome 38 and to affect the endogenous opioid system 39 , which is known to be impaired in, e.g.…”

Section: Thermal Testing In Knee Osteoarthritismentioning

confidence: 99%

The Role of Preoperative Radiologic Severity, Sensory Testing, and Temporal Summation on Chronic Postoperative Pain Following Total Knee Arthroplasty

Petersen

Simonsen

Laursen

et al. 2018

The Clinical Journal of Pain

115

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Objectives: Knee osteoarthritis (KOA) can be associated with local and central sensitization. As an indicator of the central gain, facilitated temporal summation of pain (TSP) has been found in KOA patients. This facilitation is predictive of the development of chronic postoperative pain after total knee arthroplasty (TKA). Other studies have suggested hypoesthesia/hypoalgesia to thermal stimuli as a feature in KOA. This study investigated associations between preoperative TSP, thermal sensitivity, and radiologic severity for the development of chronic postoperative pain after TKA. Methods: Radiologic KOA (Kellgren and Lawrence), TSP, and thermal stimuli were collected, preoperatively. Clinical knee pain intensity (VAS 0-10) was assessed before and 12 months following TKA. Patients were categorized into a chronic postoperative pain group if they experienced <30% pain reduction of the initial pain after 12 months. Results: In total, 19% of the patients were categorized as chronic pain patients and presented facilitated preoperative TSP (P<0.05) and a trend towards increased heat pain threshold (P=0.077) compared with patients with normal recovery. Pearson correlations found that preoperative TSP (R=0.193; P=0.013), Kellgren and Lawrence (R=−0.168; P=0.027), warm detection threshold (R=0.195; P=0.012), and heat pain threshold (R=0.196; P=0.012) were associated with pain intensity 12 months after TKA where TSP was identified as an independent factor. Discussion: This study showed that preoperatively facilitated TSP in KOA patients was predictive of the development of chronic postoperative pain following TKA. Furthermore, this study is the first to find an association between preoperative hypoalgesia to heat and the development of chronic postoperative pain following TKA.

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Increased cutaneous miR-let-7d expression correlates with small nerve fiber pathology in patients with fibromyalgia syndrome

Cited by 60 publications

References 85 publications

Pain Processing and Vegetative Dysfunction in Fibromyalgia: A Study by Sympathetic Skin Response and Laser Evoked Potentials

Pain Processing and Vegetative Dysfunction in Fibromyalgia: A Study by Sympathetic Skin Response and Laser Evoked Potentials

Reduced association between dendritic cells and corneal sub‐basal nerve fibers in patients with fibromyalgia syndrome

The Role of Preoperative Radiologic Severity, Sensory Testing, and Temporal Summation on Chronic Postoperative Pain Following Total Knee Arthroplasty

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