BETHESDA, MD. — A growing body of research suggests dysfunction of the small-fiber axons that mediate pain sensation and autonomic function underlies complex regional pain syndrome, Dr. Anne Louise Oaklander said at a meeting sponsored by the National Institutes of Health's Pain Consortium.
Complex regional pain syndrome (CRPS) is “one of the most mysterious of the pain disorders,” said Dr. Oaklander, a neurologist at Harvard Medical School and director of the nerve injury unit at Massachusetts General Hospital, Boston. With no known cause, few physicians are willing to treat it. Others believe it to be psychosomatic. However, “we are beginning to understand the disease biology,” she said. “It's time to abandon the dichotomy between CRPS I and CRPS II [and to] consider changing the name to 'posttraumatic neuralgia.'
“Small-fiber axonopathy is what causes this,” Dr. Oaklander said.
Current diagnostic criteria for CRPS include the occurrence of a noxious event or other cause of immobilization; continuing or disproportionate pain, allodynia, or hyperalgesia; and edema, changes in skin blood flow, or abnormal sweating in the region of pain.
Most patients are classified as CRPS-I (no known nerve injury); fewer than 10% receive a diagnosis of CRPS-II (a known nerve injury). However, “a physician trained to diagnose nerve injuries can identify minor nerve injuries in most CRPS-1 patients as well,” she said.
CRPS is “what I call a focal 'pain-plus' syndrome. Patients have chronic pain but also vascular dysregulation and sometimes dystonia, contralesional 'mirror' pain … osteopenia, [and focal changes in other innervated tissues],” Dr. Oaklander said. “[The disease] reflects pathological processes, not normal pain mechanisms.”
Most patients with CRPS are young (average age 39) and female (a 4:1 ratio). Most recover spontaneously.
Skin biopsies done in Dr. Oaklander's lab of 18 CRPS-I patients show 30% fewer small-fiber nerve endings in painful CRPS-affected areas.
The identification of posttraumatic small-fiber loss in patients with CRPS was first described in 1996 and has been validated by other researchers, she noted. There is good evidence that trauma disproportionately damages small fibers, probably because they lack protective myelin and saltatory conduction. Pain results when undamaged axons within the same nerve, as well as regenerating axon spouts, malfunction, firing without cause, for instance, triggering neurogenic edema and tissue ischemia. “The problem isn't so much with the nociceptive fibers that are degenerated—it's with their neighbors, and the effects on the central nervous system,” Dr. Oaklander said. “We really can't assume that it takes a severe injury to leave someone with chronic pain—in fact, the opposite may be true.”
A swollen ankle and shallow ulcers are caused by neurogenic edema. Courtesy Dr. Anne Louise Oaklander