Central amplification may explain the heterogeneous constellation of symptoms commonly seen in fibromyalgia as well as the chronic widespread pain and tenderness. Patients with fibromyalgia exhibit a decreased threshold/increased sensitivity to heat, cold, and auditory and electrical stimuli, suggesting a central sensory augmentation in addition to central pain augmentation.25 This phenomenon may help to explain some of the symptoms that frequently accompany fibromyalgia such as sensitivity to weather changes. In addition, many of the same neurotransmitters like serotonin and norepinephrine that are thought to be involved in central pain processing also influence mood, energy, and sleep.26 Similar imbalances of these neurotransmitters in different brain regions may help to explain mood disturbances, disrupted sleep, fatigue, and cognitive dysfunction that are commonly associated with fibromyalgia. Additionally, fibromyalgia is often accompanied by other pain disorders that may also share certain central pathophysiologic features with fibromyalgia, including irritable bowel syndrome, tension-type headache and migraine, interstitial cystitis/painful bladder syndrome/chronic prostatitis/prostadynia, temporomandibular disorder (TMD), chronic pelvic pain, and vulvodynia.7 The presence of these other symptoms or comorbid disorders in addition to chronic widespread pain should raise suspicion of fibromyalgia.27 Indeed, the presence of associated symptoms is a key component of the revised 2010 ACR criteria in which chronic widespread pain in addition to features such as fatigue, disturbed sleep, cognitive symptoms, and the extent of somatic symptoms are used to identify patients with fibromyalgia in clinical settings.28 Recent advances in the understanding of the etiology and epidemiology of fibromyalgia must be applied in clinical practice to appropriately diagnose and manage patients.
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Impact on Patient Management
The recognition that peripheral nociceptive and central non-nociceptive factors may contribute to chronic pain has expanded treatment approaches across chronic pain disorders. Pharmacologic agents that act centrally in ascending and/or descending pain processing pathways are effective in many patients with fibromyalgia and in other conditions involving central pain and sensory amplification.6 Response to treatment with a centrally acting agent may also clarify the potential role of central non-nociceptive factors in individual patients. The analgesic properties of pregabalin and gabapentin, both of which are alpha-2-delta ligands that are currently used in the treatment of fibromyalgia, are hypothetically linked to reduction in the release of pronociceptive transmitters, glutamate and substance P.29 Pregabalin is approved by the Food and Drug Administration (FDA) for the management of fibromyalgia. Medications that increase the availability of norepinephrine and serotonin in the descending pain modulatory pathways may also promote pain inhibition centrally. Duloxetine and milnacipran are selective serotonin and norephinephrine reuptake inhibitors (SNRIs) that are approved by the FDA for the management of fibromyalgia.30,31
Other chronic central pain disorders, such as chronic headache, irritable bowel syndrome, temporomandibular disorders, and chronic low back pain, also respond to medications that enhance neurotransmission of serotonin and norepinephrine, supporting the concept of a central pain mechanism affecting overall pain sensitivity.32, 33, 34, 35 In addition, migraine and neuropathic pain respond to the alpha-2-delta ligands.36, 37, 38 Both gabapentin and pregabalin are also FDA-approved treatments for postherpetic neuralgia, and pregabalin is approved for the treatment of diabetic peripheral neuropathic pain.39
Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are analgesics that act primarily through peripheral mechanisms and appear to be less effective for central pain conditions such as fibromyalgia than they are for pain due to peripheral nociceptive input. However, these peripherally acting pain medications may be appropriate in certain circumstances in patients with fibromyalgia. For example, they may be used to treat concurrent peripheral pain due to damage or inflammation of tissues from certain disorders like osteoarthritis or rheumatoid arthritis, or if comorbid peripheral pain generators worsen central pain.40 Conversely, centrally acting medications may also be helpful in some individuals with pain associated with disorders historically classified as peripheral pain disorders. For example, duloxetine, a centrally acting medication, is FDA-approved for the treatment of pain associated with osteoarthritis and chronic low back pain. 30
Conclusion
Fibromyalgia is a central pain disorder that is at the end of a continuum of disorders in which central and peripheral pain mechanisms appear to play variable roles in the development of chronic pain. Fibromyalgia is distinguished by the presence of chronic widespread pain and associated symptoms such as disturbed sleep, fatigue, cognitive symptoms, and mood disturbances. The presence of other comorbid central pain disorders such as irritable bowel syndrome, tension-type headache and migraine, interstitial cystitis/painful bladder syndrome/chronic prostatitis/prostadynia, temporomandibular disorder (TMD), chronic pelvic pain, and vulvodynia is also common and should raise suspicion of fibromyalgia. Fibromyalgia can also co-occur with other peripheral nociceptive pain disorders, which requires clinicians to look beyond treatment with analgesics that act primarily through peripheral mechanisms and consider additional management with centrally acting agents to address chronic pain on multiple levels. |
