The etiology of fibromyalgia is still largely unknown, but it isn’t as controversial as it used to be.
A decade ago, the chronic rheumatic disease was most often attributed to muscle and ligament problems. Some declared it a psychogenic disorder. (Some still do.) More recently, however, studies have linked fibromyalgia with malfunctioning neurotransmitters, neurochemical imbalances and other neuropathic conditions.
“Today, it’s more widely accepted that fibromyalgia is primarily a neurogenic disease,” says Philippe Berenger, MD, a pain management specialist at Cleveland Clinic. “It still doesn’t explain the disease, but it’s a step forward.”
Dr. Berenger bolstered this belief in a presentation at Cleveland Clinic’s 18th Annual Pain Management Symposium in San Diego in March.
Definitions we can agree on
In 1994, the International Association for the Study of Pain (IASP) defined neuropathic pain as “initiated or caused by a primary lesion or dysfunction of the nervous system.” In 2008, the IASP’s Neuropathic Pain Special Interest Group tweaked the definition to include “disease of the somatosensory nervous system.”
“Fibromyalgia fits these definitions,” says Dr. Berenger. “Although the condition has no anatomically definable lesions, it is marked by altered neurological function in the spinal cord and brain. It can, therefore, be considered a dysfunction of the central inhibitory process of pain control.”
Fibromyalgia’s link to central sensitization
It’s clear that fibromyalgia has mechanisms and pathways associated with central sensitization, he notes. The condition follows similar pathways as other neuropathic pain syndromes, such as complex regional pain syndrome, interstitial cystitis and irritable bowel syndrome.
“All nerves in fibromyalgia patients are more sensitive than they should be — including the brain and spinal cord,” says Dr. Berenger. “Many patients have difficulty with concentration or have hypersensitivity to light, odors or sounds. Some have additional neuropathic pain syndromes or struggle with autonomic dysfunction, such as vasovagal symptoms.”
Central sensitization has been demonstrated in animals and humans by using various triggers (e.g., mustard oil, heat, hypertonic saline injection) to activate nociceptors in skin, viscera or muscle. Sensitization presents as:
- Tactile allodynia
- Enhanced pressure and thermal sensitivity
- Spreading to neighboring nonstimulated sites and remote regions
Increased excitability of spinal cord neurons can cause a series of events:
- Increased duration (spontaneous firing) and a growing area of response
- Abnormal neuro-anatomical reorganization (new connections between A-beta, A-delta and C fibers, which spread and involve multiple dermatomes)
- Diffuse symptoms — which can outlast the stimuli (long-term potentiation)
Newer evidence supports neurogenic claim
In 2014, researchers discovered through skin biopsy that patients with fibromyalgia had lower epidermal nerve fiber density than patients without fibromyalgia. Small fiber neuropathy, therefore, is likely another contributing factor in fibromyalgia pain — and yet more evidence that the condition has neurogenic roots, notes Dr. Berenger.
What this means for treatment
“Most of the drugs used today to treat fibromyalgia — like antidepressants and antiepileptics — are already focused on neurological targets,” says Dr. Berenger.
However, considering fibromyalgia as a central sensitization disorder opens up a larger array of treatment options, he says. Agents active on the central nervous system include:
- Sodium channel blockers
- Calcium channel blockers
- Serotonin-norepinephrine reuptake inhibitors (SNRI)
- NMDA receptor antagonists
- Nerve growth factor (NGF) inhibitors
Low-dose naltrexone is another treatment option on the horizon. One 2013 study found that the drug significantly reduced pain and improved mood and general satisfaction in people with fibromyalgia. Other studies have reported similar positive responses to the drug.
“It’s all in the mind”
Saying that fibromyalgia is “all in the mind” isn’t entirely wrong, concludes Dr. Berenger.
“Pain pathways and centers are in the brain. And we can employ techniques like mindfulness and biofeedback to control pain,” he says. “However, it’s more helpful — and accurate — to consider it a neurogenic disorder.”