Complex regional pain syndrome (CRPS) is a broad term describing excess and prolonged pain and inflammation that follows an injury to an arm or leg. CRPS has acute (recent, short-term) and chronic (lasting greater than six months) forms. CRPS used to be known as reflex sympathetic dystrophy (RSD) and causalgia. People with CRPS have changing combinations of spontaneous pain or excess pain that is much greater than normal following something as mild as a touch. Other symptoms include changes in skin color, temperature, and/or swelling on the arm or leg below the site of injury. Although CRPS improves over time, eventually going away in most people, the rare severe or prolonged cases are profoundly disabling.
Most CRPS illnesses are caused by improper function of the peripheral C-fiber nerve fibers that carry pain messages to the brain. Their excess firing also triggers inflammation designed to promote healing and rest after injury. In some people the nerve injury is obvious but in others a specialist may be needed to locate and treat the injury.
Since both types of CRPS have identical symptoms, both may be caused by nerve injury, although nerve injuries in CPRS I are typically more subtle and go unnoticed.
CRPS is more common in women but can occur in anyone at any age, with a peak around age 40. It is rare in the elderly, who have less inflammation after injury, and in young children who heal so quickly and completely.
The outcome of CRPS is highly variable:
Because of the varied symptoms, the fact that symptoms may change over time, and the difficulty finding a positive cause in some cases, CRPS is hard to treat. There is no treatment that rapidly cures CRPS.
No specific test can confirm CRPS and identify the injured nerve. Diagnosis includes:
Since CRPS generally improves over time, diagnosis is easiest early in the disorder and should not be delayed.
Most CRPS is caused by damage to, or dysfunction of, injured peripheral sensory neurons, which then has secondary effects on the spinal cord and brain. The central nervous system is composed of the brain and spinal cord; the peripheral nervous system involves nerve signaling from the brain and spinal cord to all other parts of the body.
It is unclear why some people develop CRPS while others with similar trauma do not. In more than 90 percent of cases, CRPS is triggered by nerve trauma or injury to the affected limb that damages the thinnest sensory and autonomic nerve fibers. These “small fibers”—which lack insulating thick myelin sheaths (a protective coating, like insulation that surrounds a wire)—transmit pain, itch, and temperature sensations and control the small blood vessels and health of almost all surrounding cells.
The most common actions or activities that lead to CRPS are:
Poor circulation can impede nerve and tissue healing. Damage to the small fibers that control blood flow causes many symptoms of CRPS. Blood vessels in the affected limb can dilate (open wider) to leak fluid into the surrounding tissue, causing red, swollen skin. This can deprive underlying muscles and deeper tissues of oxygen and nutrients, which can cause muscle weakness and joint pain. When skin blood vessels over-constrict (clamp down), the skin becomes cold, white, gray, or bluish.
CRPS develops only in the limbs because circulation is constrained there. Arterial blood pumped down to the hands and feet must fight gravity to return upwards in the veins to the heart. C-fiber damage can impede this, permitting blood fluids to remain in the limb where the swelling then further blocks return blood flow. Slowed circulation impedes delivery of oxygen and nutrients needed for healing and sometimes causes spreading of cellular injury. Breaking the cycle by reducing limb swelling and restoring circulation is often the key that permits recovery to begin.
Other influences on CRPS include:
Poor nerve health. Conditions such as diabetes or exposure to nerve toxins can leave the nerves less resilient. Individuals with generalized peripheral neuropathies may be unable or slow to regrow their nerve cells from an injury or stress that wouldn’t cause problems in healthy nerves. A key to CRPS recovery is improving general nerve health by removing or improving conditions that slow nerve regrowth.
Immune system involvement. The C-fiber nerve cells also communicate with immune cells to help us heal from injury. Excess or prolonged nerve signaling can dysregulate immune cells in the affected limb, as does CRPS-associated poor circulation. Some people with CRPS have elevated local levels of inflammatory chemicals called cytokines that contribute to the redness, swelling, and warmth in the CRPS-affected limb. CRPS is more common in individuals with other inflammatory and autoimmune conditions such as asthma. Some individuals with CRPS may have abnormal antibodies that promote an immune attack on small fibers.
Genetics. Genetics, along with environment, influence each person’s ability to recover from injury. Rare family clusters of CRPS have been reported. Familial CRPS may be more severe with earlier onset, greater dystonia, and the involvement of more than one limb.
Most individuals do not have all of these symptoms, and the number of symptoms typically reduces during recovery.
Most early or mild cases recover on their own. Treatment is most effective when started early.
Primary therapies that are widely used include:
Rehabilitation and physical therapy. This is the single most important treatment for CRPS. Keeping the painful limb or body part moving improves blood flow and lessens circulatory symptoms, as well as maintains flexibility, strength, and function. Rehabilitating the affected limb helps prevent or reverse secondary spinal cord and brain changes associated with disuse and chronic pain. Occupational therapy can help people learn new ways to become active and return to work and daily tasks.
Psychotherapy. People with severe CRPS often develop secondary psychological problems including depression, situational anxiety, and sometimes post-traumatic stress disorder. These heighten pain perception, further reduce activity and brain function, and make it hard for patients to seek medical care and engage in rehabilitation and recovery. Psychological treatment helps people with CRPS to feel better and better recover from CRPS.
Graded motor imagery. Individuals are taught mental exercises including how to identify left and right painful body parts while looking into a mirror and visualizing moving those painful body parts without actually moving them. This is thought to provide non-painful sensory signals to the brain that helps reverse brain changes that are prolonging CRPS.
Medications. Several classes of medication have been reported as effective for CRPS, particularly when given early in the disease. However, none are approved by the U.S. Food and Drug Administration (FDA) to be marketed specifically for CRPS, and no single drug or combination is guaranteed to be effective in everyone. Drugs often used to treat CRPS include:
Spinal cord stimulation. Stimulating electrodes are threaded through a needle into the spine outside the spinal cord. They create tingling sensations in the painful area that helps block pain sensations and normalize signaling into the spinal cord and brain. Electrodes can be placed temporarily for a few days to assess if stimulation is likely to be helpful. Minor surgery is required to implant the stimulator, battery, and electrodes under the skin on the torso. Once implanted, stimulators can be turned on and off and adjusted with an external controller.
Other types of neural stimulation. Implanted neurostimulation can be delivered at other locations including near injured nerves (peripheral nerve stimulators), under the skull (motor cortex stimulation with electrodes), and within brain pain centers (deep brain stimulation). Recent noninvasive commercially available treatments include nerve stimulation at the peroneal nerve at the knee. Another is repetitive Transcranial Magnetic Stimulation or rTMS, a noninvasive form of brain stimulation that uses a magnetic field to change electrical signaling in the brain. Similar at-home use of small transcranial direct electrical stimulators is also being investigated. These stimulation methods have the advantage of being non-invasive; however, repeated treatment sessions are needed to maintain benefit, so they require time.
Spinal-fluid drug pumps. These implanted devices deliver pain-relieving medications directly into the fluid that bathes the nerve roots and spinal cord. Typically, these are mixtures of opioids, local anesthetic agents, clonidine, and baclofen. The advantage is that very low doses can be used that do not spread beyond the spinal canal to affect other body system. This decreases side effects and increases drug effectiveness.
Alternative and holistic therapies. Based on studies from other painful conditions, some individuals are investigating accessible treatments such as medical marijuana, behavior modification, acupuncture, relaxation techniques (such as biofeedback, progressive muscle relaxation, and guided motion therapy), and chiropractic treatment. These do not benefit the primary cause of CRPS, but some people find them useful. They are generally accessible and not dangerous to try.
Limited use therapy for the most severe or non-resolving pain that has not responded to conventional treatment, such as ketamine. Some investigators report benefit from low doses of ketamine—a strong anesthetic—given intravenously for several days. In certain clinical settings, ketamine has been shown to be useful in treating pain that does not respond well to other treatments. However, it can cause delusions and other symptoms of psychosis with long-lasting impact.
Rarely used former treatments include:
Sympathetic nerve block. Previously, sympathetic blocks—in which an anesthetic is injected next to the spine to directly block the activity of sympathetic nerves and improve blood flow—were used. More recent studies demonstrate no long-lasting benefit after the injected anesthetic wears off and there is the risk of injury from needle injections, so this approach has fallen from favor.
Surgical sympathectomy. This destroys some of the nerves that carry pain signals. Use is controversial; some experts think it is unwarranted and makes CRPS worse, while others report occasional favorable outcome. Sympathectomy should be used only in individuals whose pain is temporarily dramatically relieved by sympathetic nerve blocks.
Cutting injured nerves or nerve roots. People with CRPS often ask if cutting the damaged nerve above the site of injury would end the pain. In fact, this causes a larger nerve lesion that will affect a larger area of the limb. Also, the spinal cord and brain react badly to being deprived of stimulation which can result in central pain syndromes. Other than in exceptional circumstances such as palliative care, this should not be performed.
Amputating the painful lower limb. This is an even more drastic and disabling form of nerve cutting, and the consequences are irreversible, whereas CRPS almost always improves over time, albeit sometimes slowly. Amputation is thus not appropriate for pain control alone, but it is rarely required to manage bone infection or to permit use of a prosthesis for long-affected non-recovering individuals. This last resort should not be performed without input from several specialists along with psychological counseling.