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MGH

Published On May 17, 2018

BASIC RESEARCH

A (Small) Cause of Big Pain

Neurologist Anne Louise Oaklander investigates a cause of chronic pain that is treatable without opioids.

For many patients and their physicians, opioids still seem to be the most effective way to relieve chronic pain. But what if an opioid prescription—and its risks of addiction—could be sidestepped by finding a more precise diagnosis and treatment?

Anne Louise Oaklander, director of the Nerve Unit and neurodiagnostic skin biopsy lab at Massachusetts General Hospital, looks at a common condition called small-fiber polyneuropathy (SFPN), which is characterized by several unexplained, unprompted symptoms, including chronic pain. By diagnosing and treating SFPN directly, says Oaklander, physicians could reduce the need for addictive opioids that only temporarily dampen pain.

Q: What is small-fiber polyneuropathy?

A: Polyneuropathy describes a family of conditions in which the nerve fibers that run throughout the body are damaged. There are two types of fibers—small and large diameter—and until now, medicine has focused almost exclusively on disorders that affect the large fibers, because these are easier to study and diagnose. But more than 80% of our peripheral nerve fibers are small, and one of their jobs is to sense and transmit pain signals. Small-fiber polyneuropathy is when these fibers are “sick” and spontaneously misfire, sending pain signals to the brain even when there’s no threat. By identifying the underlying causes of SFPN, we can actually improve symptoms and sometimes cure these patients with previously unexplained chronic pain—rather than just giving them painkillers.

Q: Why hasn’t this approach been used before?

A: The research just wasn’t there; these are new medical discoveries. For example, my team at MGH published a study in 2013 that suggests SFPN underlies 40% of cases of fibromyalgia, which affects 2% to 6% of the world’s population. Before this, fibromyalgia was just a label—not associated with any disease—so there was no possibility of specific treatment. Actually identifying an underlying cause of this kind of common, but not understood, condition opens the door to a whole new world for patients, giving them the possibility of disease modifications and even cures.

Q: How likely is it that SFPN is the underlying cause of chronic pain?

A: Chronic pain affects at least 90% of confirmed cases of SFPN, but most patients have a ton of other symptoms as well, including unexplained itch and tingling, chronic fatigue, exercise intolerance, frequent headaches, gastrointestinal symptoms, feeling faint and rapid heart rate, among others. Currently, the best way to confirm SFPN—and tie these disparate symptoms to their actual cause—is through a skin biopsy taken under anesthesia from the lower leg. MGH is one of very few hospitals in the country that offer this test.

Q: What causes SFPN?

A: More than a dozen different causes have been cited in published materials. Diabetic neuropathy almost always starts with SFPN. In some cases, it’s related to something that a patient is exposed to, such as chemotherapy. But in 2013, MGH faculty Max Klein and I published a paper in Pediatrics offering the first evidence that SFPN commonly affects children and adolescents—and none had diabetes, cancer or chemotherapy-induced nerve damage. We discovered, by examining the medical records of children with unexplained pain, that these otherwise healthy kids can develop SFPN when their immune system starts to attack their small fibers.

Q: What are the implications of this discovery?

A: We have proposed a new disease, “apparently autoimmune SFPN,” which affects healthy kids and adults with the onset of chronic pain and other unexplained symptoms. And many respond to already marketed treatments for other autoimmune neuropathies. Earlier this year we published the first large study to show efficacy of intravenous immunoglobulins for apparently autoimmune SFPN. Of the 55 patients treated, about 75% felt better and showed improved nerve function, and 16% had sustained remission. But it’s important to note that not everybody who develops this neuropathy requires such intensive and expensive therapy. Many will improve on their own, particularly if their autoimmunity is transient—such as following an infection or vaccination.

Q: How might discoveries about SFPN change the approach to the opioid epidemic?

A: If we can diagnose that a person’s unexplained chronic pain is caused by SFPN, we may be able to get them off opioids or gabapentin, which just manage pain rather than addressing its cause.

Q: What do you hope physicians and patients will take away from your work?

A: I hope they change their thinking about chronic widespread pain, particularly when there are clues to suggest SFPN. Doctors contributed to this epidemic by prescribing opioids for chronic, unexplained pain. We all regret that. But now we have the chance to do better, by scrutinizing patients more carefully to identify those with SFPN, who can be much better served by diagnosing and treating it as such.