Small fibre neuropathy (SFN) is a condition that affects small nerve fibres throughout the body, leading to various sensory symptoms such as pain, “pins and needles” and burning sensation, and autonomic symptoms such as palpitations, gastrointestinal problems, and excessive sweating. Several studies discuss the association of ME/CFS with SFN, and many individuals with ME/CFS report symptoms that align with SFN, therefore it is a topic of interest.
Impaired sensory function in ME/CFS due to SFN
Researchers in Spain assessed 50 individuals with ME/CFS, 87 individuals with long COVID, and 50 healthy controls. The presence of autonomic and sensory SFN was evaluated using a Sudoscan (tool that measures nerve damage by assessing sweat gland function), contact heat evoked potentials (brain responses to thermal stimuli applied to skin), and quantitative sensory testing (measures changes in sensitivity to different sensations such as temperature, pressure, and vibration).
Both individuals with ME/CFS and those with long COVID exhibited significant differences in detection of, and response to, heat compared to healthy controls. The results indicate potential damage to types of sensory fibres known as C-type unmyelinated fibres .
SFN and dysautonomia
One study noted a high prevalence of SFN in about one third of ME/CFS patients, slightly less than the approximately 50% prevalence seen in postural orthostatic tachycardia syndrome (POTS), a type of dysautonomia (impairment of the autonomic nervous system) and a common comorbidity in ME/CFS. In POTS, individuals experience abnormal blood pooling in the legs upon standing, which is potentially due to poor constriction of veins (venoconstriction) caused by damaged small nerve fibres. Blood pooling in the legs also can mean that there is less blood returning to the heart – a condition known as preload failure which is associated with exercise intolerance. Thus, the researchers propose SFN as “the major cause of preload failure in a substantial, not yet fully measured, proportion of ME/CFS patients”.
Underlying mechanisms
Autoimmunity potentially plays a role in SFN, whereby the body’s immune system attacks its own nerves. It is also hypothesised that in ME/CFS, an excessive production of substances such as bradykinin could lead to increased blood-brain barrier permeability and cerebrospinal fluid production which in turn increases pressure on nerves leading to SFN .
In ME/CFS and mast cell activation syndrome (MCAS; another comorbidity of ME/CFS) associated SFN may reduce the production of important neuropeptides (chemical messengers) involved in dilating blood vessels. Their deficiency in ME/CFS could lead to poor blood flow to muscles, contributing to symptoms such as fatigue and pain.
Management of SFN
The treatment approach to SFN appears to be complex and dependant on multiple factors. One source states, “The management of SFN should involve treatment of the underlying etiology [sic] in patients with an identified cause of neuropathy… Pain management is important in the treatment of SFN, as neuropathic pain may be debilitating and cause a decrease in function and depression. Pain secondary to SFN is often best managed with a multidisciplinary team, which may involve a primary care physician, a pain management specialist, a neurologist, as well as a psychiatrist. Medications used in the treatment of SFN include anticonvulsants, antidepressants, topical anesthetics [sic], narcotics, non-narcotic analgesics, and antiarrhythmics, while nonpharmacologic treatments such as heat, ice, massage of painful areas, and transcutaneous electrical nerve stimulation (TENS) may also be used.”
As stated by NICE in their guideline addressing neuropathic pain, “Neuropathic pain is very challenging to manage because of the heterogeneity of its aetiologies, symptoms and underlying mechanisms…”
Conclusion
Diagnosing SFN in individuals with ME/CFS may help shift treatment approaches to more targeted therapies, addressing the underlying mechanisms involved. In managing comorbidities, such as SFN, health care providers have the opportunity to alleviate the symptom burden in ME/CFS.
Furthermore, one paper aptly states “More comprehensive evaluation is recommended to fully address SFN contribution to ME/CFS. Although neither ME/CFS nor any symptom-based syndrome is caused by only one single disease or pathophysiology, diagnosing established diseases when present shifts at least these patients to more effective clinical frameworks and facilitates detection of remaining contributors.”
