Reflex Sympathetic Dystrophy Syndrome
Complex Regional Pain Syndrome
Loss of Small Nerve Fibers in CRPS
Study Finds Loss of Small Nerve Fibers in Complex Regional Pain Syndrome (CRPS)
For release: Friday, May 19, 2006
Overview A new study shows that a reduction in small-diameter nerve fibers is evident in
the devastating chronic pain syndrome known as complex regional pain syndrome-type I
(CRPS-I), which was formerly known as reflex sympathetic dystrophy. This finding of
nerve damage could provide a biomarker, or a specific physical trait, that clinicians could
use in the future to help diagnose and measure the natural history of CRPS.
A new study shows that a reduction in small-diameter nerve fibers is evident in the
devastating chronic pain syndrome known as complex regional pain syndrome-type I
(CRPS-I), which was formerly known as reflex sympathetic dystrophy. This finding
of nerve damage could provide a biomarker, or aspecific physical trait, that
clinicians could use in the future to help diagnose and measure the natural history
The study of human skin biopsies provides some of the first evidence of a physical
abnormality underlying CRPS-I. The results are published in the February issue of the
journal Pain* and were funded in part by the National Institute of Neurological Disorders
and Stroke (NINDS).
CRPS develops when a portion of the nervous system that normally conducts pain
signals becomes electrically overactive. This phenomenon results in spontaneous
pain. In the past, many doctors believed that this mysterious pain syndrome was a
psychosomatic illness. CRPS type II, once known as causalgia, refers to pain after a
nerve injury. CRPS-type I, formerly known as reflex sympathetic dystrophy (RSD),
occurs in patients most often after trauma, but without clear nerve injury. Pain and
other symptoms persist long after the initial injury has healed. The chronic pain of CRPS-I
may emerge following a cut, burn, fracture, sprain, infection, surgery, or arthritis.
Coronary artery disease and stroke may also be associated with onset of the disorder.
Unlike conditions such as stroke, CRPS has no known risk factors and can affect anyone.
The patient's arms or legs are usually involved, but CRPS may affect any part of the body.
Patients also have other changes in the pain site such as swelling or changes in skin color
“CRPS is not really a disease process but a symptom complex. It has been difficult to
accurately identify CRPS patients,” says lead author Anne Louise Oaklander, MD, PhD,
from Massachusetts General Hospital and Harvard Medical School in Boston. “However,
absence of proof is not the proof of absence. With CRPS a great cross-section of people
can be affected, since even drawing blood can bring it on. The person can look absolutely
fine on the outside but still can suffer from devastating pain,” says Dr. Oaklander.
Currently, cases of CRPS are hard to prove or disprove. "It is difficult to see a patient who
appears to be in distress, particularly if it's severe, and who's pleading with you to help,
when you don't quite know what to do, ," Dr. Oaklander says. “Patients want an objective
cause for their symptoms to be identified.”
The typical neurology tests used to diagnose nerve injuries involve electromyography
(EMG) and nerve conduction techniques that measure major motor or sensory nerve
changes. Unfortunately the fiber nerve injuries in CRPS are not detected by this standard
exam, which only measures large-fiber function. The difficulty in measuring small-fiber
damage led Dr. Oaklander and her colleagues to propose skin biopsy for detection of
CRPS. Skin biopsy, a procedure in which a sample of skin tissue is removed and
examined, provides a very sensitive method for detecting small nerve fiber damage. “Skin
biopsies are a window into the peripheral nervous system,” says Dr. Oaklander.
In the study, small skin samples were taken from 18 adults with CRPS-I and seven people
who had chronic pain from osteoarthritis, but not CRPS. Each subject identified the
location of his or her maximum pain, a nearby symptom-free area on the same limb, and a
pain free area on the opposite limb. Skin biopsies were taken from all three spots and the
density of tiny projections extending from each nerve cell – small nerve fibers, or neurites –
was measured. The results showed a decrease in the number of neurites in the CRPS-
affected regions only. On average, about 30 percent of the neurites were missing in the
affected limbs. The loss of neurites may cause the pain of CRPS by triggering a hyper-
response on the part of the remaining neurons.
The next step for the researchers will be to create and test animal models that replicate the
unique features of CRPS. This animal model may identify other biomarkers for the
presence of the pain in CRPS patients and could improve medical care for patients with
CRPS by providing the first and most important step of identification. In the meantime, the
evidence now suggests that CRPS is a classifiable neurologic disorder. It also guides CRPS
patients to seek treatments appropriate for nerve injury.
The NINDS is a component of the National Institutes of Health (NIH) in Bethesda,
Maryland, and is the nation’s primary supporter of biomedical research on the brain and
nervous system. The NIH is comprised of 27 Institutes and Centers and is a component of
the U. S. Department of Health and Human Services. It is the primary Federal agency for
conducting and supporting basic, clinical, and translational medical research, and
investigates the causes, treatments, and cures for both common and rare diseases. For
more information about NIH and its programs, visit http://www.nih.gov.
*Oaklander AL, Rissmiller JG, Gelman LB, Zheng L, Chang Y, Gott R. “Evidence of focal
small-fiber axonal degeneration in complex regional pain syndrome-I (reflex sympathetic
dystrophy).” Pain, February 2006, Vol. 120, pp. 235-243.
-By Michelle D. Jones-London, Ph.D.
Date Last Modified: Friday, May 19, 2006
(Direct credit to the NINDS and NIH. I personally thank you!)
God Grant you the serenity to accept
the things you cannot change, the
courage to change the things that you
can and the wisdom to know the