Small-fiber neuropathy: a look at pain research

nervous system

Research into small-fiber neuropathies in rheumatic diseases is still young.

Many patients with rheumatic diseases and fibromyalgia suffer from burning pain in the extremities, sensory disturbances and other problems of the autonomic nervous system, which can manifest themselves as palpitations, early feeling of satiety when eating, bladder emptying disorders or dry skin. Until now, there were only a few treatment options.

However, a study from wurzburg (2013) opened up hope for those affected: signs of a small-fiber neuropathy were detected in skin biopsies from patients with fibromyalgia. Small fiber neuropathy is a special form of polyneuropathy that affects only the small autonomic and sensory nerve fibers. In response to these new findings, small fiber neuropathy has also been studied in many other rheumatic diseases. Small-fiber neuropathy was found to be comparatively common in rheumatic diseases such as systemic lupus erythematosus and sjogren’s syndrome.

According to a recent study, one in four people with sjogren’s syndrome also has polyneuropathies. The damage is manifested, among other things, by tingling in the hands, numbness in the feet and pain. When nerves that control muscles are affected, paralysis of the arms and legs can occur. However, it is still unclear whether the small-fiber neuropathy in rheumatic diseases is based on similar, possibly inflammatory damage to the nerve fibers or whether there are disease-specific patterns of damage.

Small-fiber neuropathy – a young field of research

Research on small fiber neuropathies in rheumatic diseases is still young. Therefore, due to the young age of this field of research, there are no good data so far. For recommendations, physicians therefore mainly rely on experience from the field of diabetes mellitus. treatment of first choice is treatment of the underlying disease.

In rheumatic diseases, this is often an immunosuppressive or immunomodulating therapy. If this does not sufficiently alleviate the symptoms, antidepressants (e.g., amitriptyline, duloxetine, venlafaxine), epilepsy drugs (e.g., gabapentin, pregabalin and now also lacosamide) or patches (e.g., capsaicin) are used for symptomatic pain treatment. In addition to this rather specific aspect of pain in rheumatic diseases, other pains also play a role.

An overview of the different types of pain and the corresponding complaints can be found in the table below. Three causes of pain in rheumatology are discussed:

  • inflammation in the sense of active inflammatory activity in the painful tissue,
  • damage in the sense of structural damage to tissues leading to pain,
  • Pain processing in the sense of perception and processing in the nervous system.

Significance in rheumatoid arthritis

Particularly in patients with rheumatoid arthritis, these three causes cannot always be reliably distinguished in practice, but they are of great importance for therapy.

  • If the pain is triggered by active inflammation in the joint, the onset of symptoms is often abrupt and is accompanied by swelling and redness of the corresponding joint.
  • Pain due to structural damage often occurs during the course of the disease, when damage to the bones is clinically and radiologically detectable.
  • Changes in pain processing often occur during the course of the disease. Pain can become chronic, and a person’s individual response to a certain pain stimulus can lead to increasing sensitization to pain as it progresses.

Possible triggers

Drugs used in rheumatology that are known to cause nerve damage.

TNF-α antagonists; leflunomide; sulfasalazine; (hydroxy-)chloroquine; colchicine; dapsone; statins; amiodarone; fluoroquinolones; methotrexate

Inflammatory causes

Neuropathic pain caused by polyneuropathy, i.e. damage to many nerve cells, or in particular by mononeuritis multiplex, i.e. damage to several nerve trunks of different localization, is particularly common in rheumatology. This is particularly relevant for people suffering from vasculitis, because inflammation in the vessels can also damage neighboring nerves. But also rheumatoid arthritis or sjogren’s syndrome can cause polyneuropathy. Chronic inflammatory reactions are seen as the causes, even if a precise mechanism is not known.

Often, however, pain in rheumatic diseases cannot be assigned to a specific dimension. Rather, they are composed of the interaction of individual factors, such as rheumatic disease history, psychological resources, social environment, concomitant diseases and medication. Therefore, in addition to a rheumatologist who minimizes the (inflammatory) activity of the underlying rheumatic disease, a pain therapist is often needed as well. This can be accompanied by a multimodal pain therapy consisting of pharmacological, physiotherapeutic and behavioral measures. In particular, it must be taken into account that people suffering from a rheumatic disease may also suffer from pain as an undesirable side effect of medication. An overview of the drugs frequently prescribed in rheumatology that can trigger pain can be found in the table on the right.

Author: dr. Elise siegert is an internal rheumatologist at the charite hospital in berlin specializing in rheumatology and clinical immunology.

Types of pain and their symptoms

Pain: nociceptive
cause: physiological pain stimulus due to tissue damage
symptoms: acute onset of pain of variable intensity

Pain: neuropathic
cause: damage to nerves
symptoms: tingling, burning, electrical shooting pain, radiating, triggered by harmless stimuli

Pain: somatic
cause: damage to skin, muscles,joints, bones, connective tissue
complaints: stabbing, if superficial, pressing or drilling, if in deep tissues

Pain: visceral
cause: damage to internal organs
Complaints: dull, penetrating pain, often colicky

pain: psychogenic
cause: unresolved problems
complaints: often headaches, muscular pain, back or abdominal pain

pain: reflex
cause: misregulation, malposition
symptoms: for example complex regional pain syndrome (CRPS), migraine, back or tension headaches

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