ArticlePain reports2017
Reduced intraepidermal nerve fiber density after a sustained increase in insular glutamate: a proof-of-concept study examining the pathogenesis of small fiber pathology in fibromyalgia.
Article in Pain reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Greater Somatosensory Afference With Acupuncture Increases Primary Somatosensory Connectivity and Alleviates Fibromyalgia Pain via Insular γ-Aminobutyric Acid: A Randomized Neuroimaging Trial.Arthritis & rheumatology (Hoboken, N.J.) · 2021Trial
- Effects ofPain reports · 2026Article
- Pain Mechanisms in Fibromyalgia: An Integrative Narrative Review of Central, Peripheral, Neuroimmune, and Psychobiological Factors.Biomedicines · 2026Review
- Uncovering Hidden Profiles: From Pain-Centric to Multi-Symptom Small Fiber Neuropathy.European journal of neurology · 2025Article
- Small Fibre Pathology in Fibromyalgia: A review.Pain and therapy · 2025Review
- Exploring the Relationship Between Brain Neurochemistry, Cervical Impairments and Pain Sensitivity in People with Migraine, Whiplash-Headache, Low Back Pain and Healthy Controls: A Secondary Analysis of a Cross-Sectional Case-Control Study.Journal of clinical medicine · 2025Article
- Small fiber pathology in fibromyalgia syndrome.Pain reports · 2025Review
- From fibrositis to fibromyalgia to nociplastic pain: how rheumatology helped get us here and where do we go from here?Annals of the rheumatic diseases · 2024Review
- Review
- Deciphering nociplastic pain: clinical features, risk factors and potential mechanisms.Nature reviews. Neurology · 2024Review
- Small fibre pathology, small fibre symptoms and pain in fibromyalgia syndrome.Scientific reports · 2024Article
- The crosstalk of the pathophysiologic models in fibromyalgia.Clinical rheumatology · 2023Review
- Decreased DTI-ALPS and choroid plexus enlargement in fibromyalgia: a preliminary multimodal MRI study.Neuroradiology · 2023Article
- Reply to 'Imbalance of threat and soothing systems in fibromyalgia: rephrasing an established mechanistic model?'Nature reviews. Rheumatology · 2023Article
- Abnormal Intraepidermal Nerve Fiber Density in Disease: A Scoping Review.medRxiv : the preprint server for health sciences · 2023Article
- Abnormal intraepidermal nerve fiber density in disease: A scoping review.Frontiers in neurology · 2023Article
- Emotion regulation and the salience network: a hypothetical integrative model of fibromyalgia.Nature reviews. Rheumatology · 2023Review
- The puzzle of fibromyalgia between central sensitization syndrome and small fiber neuropathy: a narrative review on neurophysiological and morphological evidence.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022Review
- Fibromyalgia: Pathogenesis, Mechanisms, Diagnosis and Treatment Options Update.International journal of molecular sciences · 2021Review
- Contribution of central sensitization to stress-induced spreading hyperalgesia in rats with orofacial inflammation.Molecular brain · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionNeuroimaging reveals increased glutamate within the insula of patients with fibromyalgia (FM), suggesting a link between FM symptoms and increased central excitatory neurotransmission. Many patients with FM also present with decreased intraepidermal nerve fiber density (IENFD), consistent with small fiber pathology. It remains unknown, however, whether either of these mechanistic findings represent a cause or a consequence of the other. This study tests the hypothesis that an excitatory imbalance within the insula leads to small fiber pathology.
objectivesThis is a proof-of-concept study to examine whether a chronic, bilateral increase in insular glutamate can be a causal factor in the development of small fiber neuropathy in FM.
methodsThe glutamate transport inhibitor l-trans-Pyrrolidine-2,4-dicarboxylic acid (PDC), which increases endogenous levels of glutamate, was dissolved in Ringer solution and bilaterally delivered into the insula of rats for 6 weeks. Naive rats that did not undergo any surgery or treatment and rats administered Ringer vehicle solution into the insula served as controls. Multimodal nociceptive sensitivity was assessed weekly. Hind paw tissue biopsies were collected for IENFD assessment, at the end of the experiment.
resultsCompared with controls, increasing endogenous glutamate in the insula with PDC caused sustained decreases in mechanical paw withdrawal threshold and thermal paw withdrawal latency, increased aversion to noxious mechanical stimulation, and a decrease in IENFD. Cold reactivity was not altered by PDC administration.
conclusionBilateral insular PDC administration produced a persistent increase in multimodal pain behaviors and a decrease in peripheral nerve fibers in rat. These preclinical findings offer preliminary support that insular hyperactivity may be a casual factor in the development of small fiber pathology in FM.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.