Damage to Small Nerve Fibers in the Skin: A New Way to Understand Fibromyalgia?

Newly emerging perspective in pain research helps to explain the source of pain in fibromyalgia and other widespread pain conditions. Image credit: ricochet64/ 123RF Stock Photo.

Newly emerging perspective in pain research helps to explain the source of pain in fibromyalgia and other widespread pain conditions. Image credit: ricochet64/123RF Stock Photo.

Editor’s Note: The first-ever North American Pain School (NAPS) took place from June 26-30, 2016 in Montebello, Quebec, Canada. This educational initiative brought together leading experts in pain research and management to provide 30 trainees–part of the up-and-coming generation of pain researchers–with scientific education, professional development and networking experiences. Six of the trainees were also selected to provide first-hand reporting from the event, including summaries of talks presented at the meeting. Here, Luke Legakis, an MD/PhD student at Virginia Commonwealth University, Richmond, US, summarizes a talk delivered by Anne Louise Oaklander, a neurologist and pain researcher at Massachusetts General Hospital, Boston, US. Oaklander’s talk described emerging findings that are helping to illuminate the biological basis of fibromyalgia and related pain conditions.

Fibromyalgia, and other conditions characterized by widespread pain throughout the body, have long been a mystery. Some physicians still doubt that fibromyalgia is a real disease with true biological underpinnings. Fortunately, that viewpoint is beginning to change. At the inaugural North American Pain School, Anne Louise Oaklander described research offering the first objective medical evidence for an underlying biological basis of fibromyalgia. The findings point to small-fiber polyneuropathy (SFPN) as a possible cause of pain and other symptoms.

Small fibers, large consequences
SFPN refers to damage to and dysfunction of small-diameter nerve fibers in the peripheral nervous system, which consists of nerves outside of the brain and spinal cord. These small fibers include pain sensing-neurons that detect and transmit painful sensations from the body to the spinal cord, where sensory signals are modulated and then relayed up to the brain.

Importantly, the small fibers also help to maintain proper functioning of internal organs such as the intestines, stomach, and heart. Damage to the fibers has been linked to bowel problems, abnormal sweating, rapid heart rate and drops in blood pressure upon standing (called orthostatic hypotension), among others. SFPN may even affect the brain, resulting in cognitive deficits. Because of these diverse effects, patients with SFPN may not only experience pain, but also often have disruptions in one or several organ systems.

Patients with these symptoms often receive different diagnoses, depending on the type of physician they see. For instance, a rheumatologist may make a diagnosis of fibromyalgia, while a gastroenterologist may say the pain results from irritable bowel syndrome. Other patients are left with no explanation for their troubles. But all along, the underlying cause that generates the symptoms goes unrecognized and untreated.

The first objective medical evidence for fibromyalgia
For patients with fibromyalgia, the path towards a diagnosis can be particularly frustrating, as there are no objective biological markers or tests that can confirm a diagnosis. But, new tools are beginning to emerge, and they show that fibromyalgia can in fact be characterized by objective indicators of disease, putting the condition on a sound scientific basis for the first time.

Oaklander described a recent pioneering study from her lab examining 27 adult patients with fibromyalgia. To detect the presence of SFPN, the researchers used skin biopsies, which measure the density of small nerve fibers. They also measured so-called “autonomic” functions, including heart rate, blood pressure and sweat production. Using these methods, they found that 41% of patients with fibromyalgia met the criteria for SFPN, compared to just 3% of control subjects.

In another study, Oaklander and colleagues found that of 41 patients with unexplained widespread pain (including fibromyalgia and other conditions) that first appeared before the age of 21, 98% had additional non-pain symptoms, including intestinal complaints, cardiac abnormalities, and abnormal sweating. Furthermore, skin biopsy results showed definitive evidence of SFPN in 59% of patients and probable SFPN in 17%.

“Small-fiber neuropathy is just not on the radar screen for pediatricians or those taking care of young adults,” Oaklander said, a problem that the new findings will help to correct.

Interestingly, in the young patients, there was evidence of immune system dysfunction. In fact, 80% of those patients responded to treatments that help to restore normal immune function. Oaklander also pointed to an earlier study from another group who studied four patients with SFPN. All patients showed dramatic responses to the steroid prednisone, thus providing a precedent for using treatments targeting the immune system for patients with SFPN.

In summary, Oaklander and others have demonstrated important changes in the nerves supplying the skin in some patients with fibromyalgia and other conditions characterized by chronic widespread pain—changes that can be detected with skin biopsies and autonomic function tests. But, because SFPN can be the consequence of a number of underlying conditions, such as diabetes, vitamin deficiency, cancer, and cancer treatment, treating that underlying condition is the first step.

To learn more about the causes, diagnosis and treatment of SFPN, see RELIEF related podcast with Oaklander here.

For more information about Oaklander’s work, as well as information about skin biopsies, please refer to her group’s website: http://neuropathycommons.org/