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Complex Regional Pain Syndrome (CRPS / RSD)

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Complex regional pain syndrome (CRPS) is a chronic pain condition most often affecting one of the limbs (arms, legs, hands, or feet), usually after an injury or trauma to that limb. CRPS is believed to be caused by damage to, or malfunction of, the peripheral and central nervous systems. The central nervous system is composed of the brain and spinal cord, and the peripheral nervous system involves nerve signaling from the brain and spinal cord to the rest of the body. CRPS is characterized by prolonged or excessive pain and mild or dramatic changes in skin color, temperature, and/or swelling in the affected area.

There are two similar forms, called CRPS-I and CRPS-II, with the same symptoms and treatments. CRPS-II (previously called causalgia) is the term used for patients with confirmed nerve injuries. Individuals without confirmed nerve injury are classified as having CRPS-I (previously called reflex sympathetic dystrophy syndrome). Some research has identified evidence of nerve injury in CRPS-I, so the validity of the two different forms is being investigated.

CRPS symptoms vary in severity and duration. Studies of the incidence and prevalence of the disease show that most cases are mild and individuals recover gradually with time. In more severe cases, individuals may not recover and may have long-term disability.

What are the symptoms of CRPS?

The key symptom is prolonged pain that may be constant and, in some people, extremely uncomfortable or severe. The pain may feel like a burning or “pins and needles” sensation, or as if someone is squeezing the affected limb. The pain may spread to include the entire arm or leg, even though the precipitating injury might have been only to a finger or toe. Pain can sometimes even travel to the opposite extremity. There is often increased sensitivity in the affected area, such that even light touch or contact is painful (called allodynia).

People with CRPS also experience constant or intermittent changes in temperature, skin color, and swelling of the affected limb. This is due to abnormal microcirculation caused by damage to the nerves controlling blood flow and temperature. An affected arm or leg may feel warmer or cooler compared to the opposite limb. The skin on the affected limb may change color, becoming blotchy, blue, purple, pale, or red.

Other common features of CRPS include:

  • changes in skin texture on the affected area; it may appear shiny and thin
  • abnormal sweating pattern in the affected area or surrounding areas
  • changes in nail and hair growth patterns
  • stiffness in affected joints
  • problems coordinating muscle movement, with decreased ability to move the affected body part, and
  • abnormal movement in the affected limb, most often fixed abnormal posture (called dystonia) but also tremors in or jerking of the affected limb.

How is CRPS diagnosed?

Currently there is no single diagnostic test to confirm CRPS. Diagnosis is based on the affected individual’s medical history and signs and symptoms that match the definition. But because several other conditions can cause similar symptoms, careful examination is important. Since most people improve gradually over time, diagnosis may be more difficult later in the course of the disorder.

Testing also may be used to help rule out other conditions, such as arthritis syndromes, Lyme disease, generalized muscle diseases, a clotted vein, or small nerve fiber polyneuropathies (such as from diabetes), because these require different treatment. The distinguishing feature of CRPS is usually a history of earlier injury to the affected area, as most of these other conditions are not triggered by injury. Individuals without a history of injury should be carefully examined to make sure that another treatable diagnosis is not missed.

Magnetic resonance imaging or triple-phase bone scans sometimes identify CRPS-characteristic changes in the bone metabolism. CRPS is often associated with excess bone resorption, a process in which certain cells break down the bone and release calcium into the blood.

How is CRPS treated?

The following therapies are often used:

Rehabilitation therapy. An exercise program to keep the painful limb or body part moving can improve blood flow and lessen the circulatory symptoms. Additionally, exercise can help improve the affected limb’s flexibility, strength, and function. Rehabilitating the affected limb also can help to prevent or reverse the secondary brain changes that are associated with chronic pain. Occupational therapy can help the individual learn new ways to work and perform daily tasks.  

Graded motor imagery : The strongest evidence is for graded motor imagery, which led to significant reductions in pain and swelling in patients with CRPS in three small single-center randomized controlled trials . However, a prospective observational study from two centers with a special interest in CRPS found no improvement in pain despite the use of graded motor imaging , suggesting it does not translate well into clinical practice . Physical Therapy, which can be performed twice daily at home for patients in all stages of disease, should ideally begin before limitation of movement occurs in order to maintain range of motion and prevent contractures. Resting splints for the affected limb are sometimes used with a goal of preventing progressive joint contractures.

Psychotherapy. CRPS and other painful and disabling conditions often are associated with profound psychological symptoms for affected individuals and their families. People with CRPS may develop depression, anxiety, or post-traumatic stress disorder, all of which heighten the perception of pain and make rehabilitation efforts more difficult. Treating these secondary conditions is important for helping people cope and recover from CRPS.

Medications. Several different classes of medication have been shown to be effective for CRPS, particularly when used early in the course of the disease. No drug is approved by the U.S. Food and Drug Administration specifically for CRPS. No single drug or combination of drugs is guaranteed to be effective in every person. Drugs to treat CRPS include:

  • non-steroidal anti-inflammatory drugs to treat moderate pain, including over-the-counter aspirin, ibuprofen, and naproxin
  • corticosteroids that treat inflammation/swelling and edema, such as prednisolone and methylprednisolone (used mostly in the early stages of CRPS)
  • drugs initially developed to treat seizures or depression but now shown to be effective for neuropathic pain, such as gabapentin, pregabalin, amitriptyline, nortriptyline, and duloxetine.
  • Bisphosphonates — Bisphosphonates may be effective for reducing pain in patients with early CRPS who have abnormal uptake on bone scan, even though their positive effects in this condition are probably not related to their antiresorptive properties . Supporting evidence comes from several small placebo-controlled randomized trials, including trials of intravenous and oral alendronate, intravenous neridronate, intravenous pamidronate, and intravenous clodronate. Four of these trials enrolled only patients who had evidence of osteopenic or osteoporotic changes in the affected limb .
  • botulinum toxin injections
  • opioids such as oxycontin, morphine, hydrocodone, fentanyl, and vicodin
  • N-methyl-D-aspartate (NMDA) receptor antagonists such as dextromethorphan and ketamine
  • nasal calcitonin, especially for deep bone pain, and
  • topical local anesthetic creams and patches such as lidocaine.
  • Alpha-adrenergic antagonists and agonists – Sympathetically maintained pain may respond to the addition of an alpha-1 adrenoceptor antagonist, which is supported by the clinical experience of the author and other experts . Some benefit in some patients with the use of either prazosin (1 to 6 mg/day as tolerated) or phenoxybenzamine (10 to 30 mg/day as tolerated). Hypotension can be a limiting side effect of alpha-adrenergic blockers. The author has also treated patients using a clonidine patch (0.1 mg), which is changed every seven days, usually in combination with anticonvulsants and/or antidepressants; this approach has generally not resulted in significant side effects.

All drugs or combination of drugs can have various side effects such as drowsiness, dizziness, increased heartbeat, and impaired memory. Inform a healthcare professional of any changes once drug therapy begins.

Sympathetic nerve block. Some individuals report temporary pain relief from sympathetic nerve blocks, but there is no published evidence of long-term benefit. Sympathetic blocks involve injecting an anesthetic next to the spine to directly block the activity of sympathetic nerves and improve blood flow.

Surgical sympathectomy. The use of this operation that destroys some of the nerves is controversial. Some experts think it is unwarranted and makes CRPS worse; others report a favorable outcome. Sympathectomy should be used only in individuals whose pain is dramatically relieved (although temporarily) by sympathetic nerve blocks. It also can reduce excess sweating.

Spinal cord stimulation. Placing stimulating electrodes through a needle into the spine near the spinal cord provides a tingling sensation in the painful area. Typically the electrode is placed temporarily for a few days to assess whether stimulation will be helpful. Minor surgery is required to implant all the parts under the skin on the torso. Once implanted, the stimulator can be turned on and off, and adjusted using an external controller. Data shows that about one-fourth of individuals develop equipment problems that may require additional surgeries.

Other types of neural stimulation.Neurostimulation can be delivered at other locations along the pain pathway, not only at the spinal cord. These include near injured nerves (peripheral nerve stimulators), outside the membranes of the brain (motor cortex stimulation with dural electrodes), and within the parts of the brain that control pain (deep brain stimulation). A recent option involves the use of magnetic currents applied externally to the brain (called repetitive Transcranial Magnetic Stimulation, or rTMS). The advantage is that no surgery is required; the disadvantage is need for repeated treatment sessions.

Intrathecal drug pumps. These devices pump pain-relieving medications directly into the fluid that bathes the spinal cord, typically opioids and local anesthetic agents such as clonidine and baclofen. The advantage is that pain-signaling targets in the spinal cord can be reached using doses far lower than those required for oral administration, which decreases side effects and increases drug effectiveness. There are no studies that show benefit specifically for CRPS.

Emerging treatments for CRPS include:

  • Intravenous immunoglobulin (IVIG). Researchers in Great Britain reported that low-dose IVIG reduced pain intensity in a small trial of 13 patients with CRPS for 6 to 30 months who did not respond well to other treatments. Those who received IVIG had a greater decrease in pain scores than those receiving saline during the following 14 days after infusion. A larger study involving individuals with acute-phase CRPS is planned.
  • Ketamine. Investigators are using low doses of ketamine—a strong anesthetic—given intravenously for several days to either reduce substantially or eliminate the chronic pain of CRPS. In certain clinical settings, ketamine has been shown to be useful in treating pain that does not respond well to other treatments. Dr. Sendi is the leading provider of Ketamine Therapies in Virginia. NOVA Health Recovery 703-844-0184

Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists.AUCohen SP, Bhatia A, Buvanendran A, Schwenk ES, Wasan AD, Hurley RW, Viscusi ER, Narouze S, Davis FN, Ritchie EC, Lubenow TR, Hooten WM SOReg Anesth Pain Med. 2018;43(5):521. BACKGROUNDOver the past 2 decades, the use of intravenous ketamine infusions as a treatment for chronic pain has increased dramatically, with wide variation in patient selection, dosing, and monitoring. This has led to a chorus of calls from various sources for the development of consensus guidelines.METHODSIn November 2016, the charge for developing consensus guidelines was approved by the boards of directors of the American Society of Regional Anesthesia and Pain Medicine and, shortly thereafter, the American Academy of Pain Medicine. In late 2017, the completed document was sent to the American Society of Anesthesiologists’ Committees on Pain Medicine and Standards and Practice Parameters, after which additional modifications were made. Panel members were selected by the committee chair and both boards of directors based on their expertise in evaluating clinical trials, past research experience, and clinical experience in developing protocols and treating patients with ketamine. Questions were developed and refined by the committee, and the groups responsible for addressing each question consisted of modules composed of 3 to 5 panel members in addition to the committee chair. Once a preliminary consensus was achieved, sections were sent to the entire panel, and further revisions were made. In addition to consensus guidelines, a comprehensive narrative review was performed, which formed part of the basis for guidelines.RESULTSGuidelines were prepared for the following areas: indications; contraindications; whether there was evidence for a dose-response relationship, or a minimum or therapeutic dose range; whether oral ketamine or another N-methyl-D-aspartate receptor antagonist was a reasonable treatment option as a follow-up to infusions; preinfusion testing requirements; settings and personnel necessary to administer and monitor treatment; the use of preemptive and rescue medications to address adverse effects; and what constitutes a positive treatment response. The group was able to reach consensus on all questions. CONCLUSIONS Evidence supports the use of ketamine for chronic pain, but the level of evidence varies by condition and dose range. Most studies evaluating the efficacy of ketamine were small and uncontrolled and were either unblinded or ineffectively blinded. Adverse effects were few and the rate of serious adverse effects was similar to placebo in most studies, with higher dosages and more frequent infusions associated with greater risks. Larger studies, evaluating a wider variety of conditions, are needed to better quantify efficacy, improve patient selection, refine the therapeutic dose range, determine the effectiveness of nonintravenous ketamine alternatives, and develop a greater understanding of the long-term risks of repeated treatments.

  • Hyperbaric oxygen. Several studies have investigated the use of hyperbaric oxygen therapy for chronic pain. Individuals lie down in a tank containing pressurized air, which delivers more oxygen to the body’s organs and tissues. Although research is still experimental, some researchers report hyperbaric oxygen can reduce swelling and pain, and improve range of motion in individuals with CRPS.

Several alternative therapies have been used to treat other painful conditions. Options include behavior modification, acupuncture, relaxation techniques (such as biofeedback, progressive muscle relaxation, and guided motion therapy), and chiropractic treatment.

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