Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Dec;13(6):1541-1558.
doi: 10.1007/s40122-024-00646-x. Epub 2024 Sep 12.

Idiopathic Distal Sensory Polyneuropathy and Fibromyalgia Syndrome: A Comparative Phenotyping Study

Jamie Burgess  1   2 , Anne Marshall  3 , Leandros Rapteas  3 , David Riley  3   4 , Kohei Matsumoto  4 , Cheng Boon  5 , Alia Alchawaf  6 , Maryam Ferdousi  7 , Rayaz A Malik  8 , Andrew Marshall  3   9   10 , Stephen Kaye  11 , David Gosal  12 , Bernhard Frank  3   13   10 , Uazman Alam  3   10   14   15
Affiliations

Idiopathic Distal Sensory Polyneuropathy and Fibromyalgia Syndrome: A Comparative Phenotyping Study

Jamie Burgess et al. Pain Ther. 2024 Dec.

Abstract

Introduction: Painful idiopathic distal sensory polyneuropathy (IDSP) and fibromyalgia syndrome (FMS) are cryptogenic chronic pain syndromes. The contribution of small fibre pathology (SFP) in FMS remains controversial. This study aims to quantify small nerve pathology in participants with IDSP and FMS and identify relationships of SFP with sensory phenotypes.

Methods: In this study, 73 individuals (FMS: 25, IDSP: 23, healthy volunteers: 25) underwent comprehensive assessment, including neurological exams, questionnaires, sensory tests, and corneal confocal microscopy.

Results: IDSP participants displayed lower wind-up ratio (WUR) relative to FMS (p < 0.001), loss of function to thermal and mechanical stimuli and elevated neuropathy disability scores compared to FMS and healthy volunteers (all p < 0.001). FMS participants demonstrated gain of function to heat and blunt pressure pain responses relative to IDSP, and healthy volunteers (heat: p = 0.002 and p = 0.003; pressure: both p < 0.001) and WUR (both p < 0.001). FMS participants exhibited reduced corneal nerve fibre density (p = 0.02), while IDSP participants had lower global corneal nerve measures (density, branch density, and length) relative to healthy volunteers (all p < 0.001). Utilising corneal nerve fibre length, SFP was demonstrated in 66.6% of participants (FMS: 13/25; IDSP: 22/23).

Conclusion: Participants with SFP, in both FMS and IDSP, reported symptoms indicative of small nerve fibre disease. Although distinctions in pain distributions are evident between individuals with FMS and IDSP, over 50% of participants between the two conditions displayed both a loss and gain of thermal and mechanical function suggestive of shared mechanisms. However, sensory phenotypes were associated with the presence of SFP in IDSP but not in FMS.

Keywords: Corneal confocal microscopy; Fibromyalgia syndrome; Idiopathic distal sensory polyneuropathy; Neuropathic pain; Pain characteristics; Quantitative sensory testing; Sensory phenotyping; Small fibre.

Plain language summary

In people with painful idiopathic neuropathy (pain related to nerve damage where the cause of nerve damage is unknown), fibromyalgia syndrome (a long-term condition causing widespread pain), and healthy volunteers, the small nerve fibres of the peripheral nervous system, which may be involved in generating pain were assessed. These nerve fibres can be measured at the front of the eye (cornea) which can provide details on whether they are damaged in the body. The response to temperature, light touch, pressure and pinprick stimuli can also be used to determine if there is a loss or gain of sensation, which may contribute to pain. The aim of this study was to identify the degree of damage to these nerve fibres and to determine whether this damage is associated with a loss (cannot feel or requires more intense stimulus to feel) or gain (stimulus is felt earlier or is painful earlier at lower intensity) of sensory function. The pattern of loss or gain in sensory function is known as a sensory phenotype. It was found that people with painful idiopathic neuropathy had more severe nerve damage, loss of function to temperature and touch, and fewer small nerve fibres in the cornea compared to those with fibromyalgia syndrome and healthy volunteers. People with fibromyalgia syndrome were more sensitive to heat and pressure and had fewer corneal nerve fibres relative to healthy volunteers. The presence of corneal nerve fibre damage was associated with sensory phenotypes (types of sensation felt) in painful idiopathic neuropathy but not in fibromyalgia syndrome.

PubMed Disclaimer

Conflict of interest statement

All authors; Jamie Burgess, Anne Marshall, Leandros Rapteas, David Riley, Kohei Matsumoto, Cheng Boon, Alia Alchawaf, Maryam Ferdousi, Rayaz A. Malik, Andrew Marshall, Stephen Kaye, David Gosal and Bernhard Frank declare that they have no competing interests relevant to the current publication. Uazman Alam has no direct conflict of interest but discloses the following: honoraria received from Procter & Gamble, Viatris, Eli Lilly, Grunenthal, and Sanofi for educational meetings; investigator-led funding from Procter & Gamble; and sponsorship for travel to an international conference from Daiichi Sankyo.

Figures

Fig. 1
Fig. 1
Summary of self-reported outcomes of participants with Idiopathic Distal Sensory Polyneuropathy (IDSP) and fibromyalgia syndrome (FMS). A Participants with IDSP presented with an acral pain distribution which more frequently involved both the feet and hands. B Participants with FMS more frequently reported symptoms across three or more regions including distal and proximal regions of the body. C Participants with FMS and IDSP reported radiating pains at a similar rate but elected different dynamic descriptors of their pain. The most frequently elected pain dynamic in participants with IDSP was ‘pain attacks with pain between them’ while participants with FMS commonly elected 'persistent pain with pain attacks' to represent their pain. D Diverging bar chart showing the McGill Short-Form Pain Questionnaire (MPQ) descriptors of participants with FMS (left) and IDSP (right). E Diverging bar chart showing the Pain Detect Questionnaire (PDQ) responses of participants with FMS (left) and IDSP (right). F Diverging bar chart showing the frequency of SFNSL symptoms reported. G Diverging bar chart showing the seriousness of SFNSL symptoms reported
Fig. 2
Fig. 2
Quantitative sensory testing (QST) and corneal confocal microscopy measures (CCM) in participants with idiopathic distal sensory polyneuropathy (IDSP) and fibromyalgia syndrome (FMS). Top The Z-scores of individual participants by group of thermal (A) and mechanical (B) QST measures represented as a dot plot. The error bars indicate the 95% confidence interval. Idiopathic SFN idiopathic small fibre neuropathy (orange); FMS fibromyalgia syndrome (green); HV healthy volunteers (dark blue). Bottom Representative CCM images (C left) from a healthy volunteer, a participant with fibromyalgia syndrome (FMS) and idiopathic distal sensory polyneuropathy (IDSP). CCM measurements from individual participants by group represented as a raincloud plot. The raincloud plot is a box plot with individual data points with the group distribution represented as a ‘raincloud’. As can be seen, there appears to be a binomial distribution in corneal nerve branch density in the fibromyalgia syndrome group. CDT cold detection threshold, CNBD corneal nerve branch density, CNFD corneal nerve fibre density, CNFL corneal nerve fibre length, CPT cold pain threshold, HPT heat pain threshold, MDT mechanical detection threshold, MPS mechanical pain sensitivity, MPT mechanical pain threshold, PPT pressure pain threshold, TSL thermal sensory limen, VDT vibration detection threshold, WDT warm detection threshold, WUR wind-up ratio
See this image and copyright information in PMC

References

    1. Freeman R, Gewandter JS, Faber CG, Gibbons C, Haroutounian S, Lauria G, Levine T, Malik RA, Singleton JR, Smith AG, Bell J, Dworkin RH, Feldman E, Herrmann DN, Hoke A, Kolb N, Mansikka H, Oaklander AL, Peltier A, Polydefkis M, Ritt E, Russell JW, Sainati S, Steiner D, Treister R, Üçeyler N. Idiopathic distal sensory polyneuropathy. Neurology. 2020;95(22):1005. - PMC - PubMed
    1. Marques AP, Santo ASE, Berssaneti AA, Matsutani LA, Yuan SLK. Prevalence of fibromyalgia: literature review update. Revista Brasileira de Reumatologia (English Edition). 2017;57(4):356–63. - PubMed
    1. Häuser W, Brähler E, Ablin J, Wolfe F. Modified 2016 American College of Rheumatology Fibromyalgia Criteria, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks-American Pain Society Pain Taxonomy, and the prevalence of fibromyalgia. Arthritis Care Res (Hoboken). 2021;73(5):617–25. - PubMed
    1. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011;152(3 Suppl):S2-s15. - PMC - PubMed
    1. Affaitati G, Costantini R, Fabrizio A, Lapenna D, Tafuri E, Giamberardino MA. Effects of treatment of peripheral pain generators in fibromyalgia patients. Eur J Pain. 2011;15(1):61–9. - PubMed

LinkOut - more resources