Saturday, December 20, 2014

Small Fiber Peripheral Neuropathy Found to Underlie Pain in Some Gulf War Illness Patients

The following journal article about diagnosable small-fiber peripheral neuropathy (SFPN) underlying chronic pain and multi-system symptoms, is based in part on Gulf War Illness research funded under the treatment-focused Gulf War Illness Congressionally Directed Medical Research Program (CDMRP) and Fiscal Year 2009 funding.  [GW093049]

This CDMRP vignette with Dr. Oaklander provides additional insight into the CDMRP-funded research project:

In another study reported earlier this year (M. Li et al, "Self-reported post-exertional fatigue in Gulf War veterans: roles of autonomic testing,", SFPN was also found in some -- but not a majority -- of Gulf War Illness patients. 

And, these 91outcomes articles describe published journal articles on SFPN in fibromyalgia, a neurological condition that includes chronic widespread pain as a core symptom:

It is becoming clear that differential diagnosis for pain in Gulf War veterans with chronic pain should include comprehensive testing for the possible presence of SFPN.

This 2010 91outcomes article discusses testing available (at that time) for SFPN:



SOURCE:  Molecular Pain, Dr. Anne L. Oaklander et al, published December 15, 2014


Open AccessOral presentation

Small-fiber polyneuropathy (SFPN), a common underlying diagnosis in syndromes involving unexplained chronic pain and multi-system symptoms

Anne Louise Oaklander12*Heather Downs1Zeva Daniela Herzog1 and Max Klein1
  • *Corresponding author: Anne L Oaklander 

1Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
2Departments of Pathology (Neuropathology), Massachusetts General Hospital, Boston, MA 02114, USA
For all author emails, please log on.

Molecular Pain 2014, 10(Suppl 1):O12  doi:10.1186/1744-8069-10-S1-O12
The electronic version of this article is the complete one and can be found online at:

Published:15 December 2014
© 2014 Oaklander et al; licensee BioMed Central Ltd. 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.


Syndromes involving unexplained chronic widespread pain (CWP) and multi-system symptoms are common, with 1-5% prevalence for fibromyalgia alone. They more often affect females and cause disability and high costs [1-3]. Other common syndromes include chronic fatigue, seronegative Lyme, and Gulf War Illness. Fragmentary syndromes include TMJD, POTS, CRPS, irritable bowel). These syndromes are particularly devastating in children and young adults, where they interfere with education and development and disrupt entire families [4-6]. SFPN is known to cause CWP and multi-system complaints in older adults. Unlike the syndromes above, SFPN can be objectively diagnosed by measuring innervation in lower-leg skin biopsies, and autonomic functions testing (AFT) of heart rate, blood pressure and sweating [7]. SFPN has several established causes including diabetes, infections, cancer, and toxins. Many causes are diagnosable, treatable, and sometimes curable [8]. Our work suggests that unrecognized SFPN contributes to several syndromes involving CWP and multi-organ symptoms.

Materials and methods

With IRB permission, we retrospective analyzed the medical records of 41 patients with onset of unexplained CWP and multisymptoms before age 21; most had objective testing for SFPN [9]. We also prospectively studied 27 adult patients with fibromyalgia and 30 healthy volunteers using history, examination, skin biopsies and AFT [10].


Retrospective chart review identified definite (in 59%) and probable SFPN (in 17%) among the young patients with onset before age 21 [9]. We characterized the clinical features, diagnostic, and treatment options for this new early-onset SFPN. Studying children, who lacked the typical causes of late-onset SFPN, implicated autoimmune causality in most. Among patients treated with immunomodulatory therapies, pain and other symptoms improved in 2/3 [9]. Among adults with fibromyalgia, 41% of skin biopsies from subjects with fibromyalgia vs. 3% of biopsies from controls were diagnostic for SFPN, and symptom and examination scores were higher in fibromyalgia subjects than in controls (all P ≤ 0.001) [10]. All fibromyalgia patients diagnosed with SFPN then had blood tests for all known causes [8]. None had diabetes but 62% had test-results consistent with dysimmunity, and some had genetic causes [10]. Other laboratories have now also linked fibromyalgia to SFPN [11-15].


Some patients with unexplained widespread pain and multi-system syndromes such as fibromyalgia have objectively diagnosable SFPN. SFPN can affect children and young adults, not just older adults. Multiple lines of evidence suggest that early-onset SFPN has novel causes that can be treated. The prevalence of SFPN among TMJD patients is unstudied.


None of the authors have any conflicts of interest.


Supported in part by the NIH (NINDS K24NS059892, Department of Defense grant GW093049, and donations from the Bradley, Collman, and Cheever Powell family foundations.


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1 comment:

Gary said...

I was recently tested and found to have Small Fiber Neuropathy at the NJ WRIISC. No one has been able to tell me much about this. It's been good to find this information and I wonder if this is more a link to my fibromyalgia pain.