Complex regional pain syndrome
Complex regional pain syndrome (CRPS Type 1 and Type 2) is a severe form of chronic pain, in which pain from a physical trauma outlasts the expected recovery time. The symptoms of types 1 and 2 are the same except type 2 is associated with nerve injury.
"CRPS" redirects here. For common redundant power supply, see Redundancy (engineering). For the accuracy measure, see Continuous ranked probability score.Complex regional pain syndrome
Algodystrophy; Amplified musculoskeletal pain syndrome; hyponym: reflex sympathetic dystrophy (RSD); hyponym: causalgia; hyponym: reflex neurovascular dystrophy (RND)
Pain, allodynia, hypo- or hyperesthesia, skin temperature abnormalities, atrophy, stiffness
Physical therapy (more effective with early diagnosis); medications (e.g., anticonvulsants, opioids, muscle relaxers, etc.); sympathetic nerve blockade; ketamine infusions; lidocaine infusions; implantable pharmaceuticals; amputation
Anticonvulsants (e.g., gabapentin); muscle relaxers (e.g., baclofen), ketamine or lidocaine infusions
Usually starting in a limb, CRPS manifests as pain, swelling, limited range of motion, and/or changes to the skin and bones. It may initially affect one limb and then spread throughout the body; 35% of affected individuals report symptoms throughout the body.[1] Two types are thought to exist: CRPS type 1 (previously referred to as reflex sympathetic dystrophy) and CRPS type 2 (previously referred to as causalgia). It is possible to have both types.[2]
Amplified musculoskeletal pain syndrome, a condition that is similar to CRPS, primarily affects pediatric patients, falls under rheumatology and pediatrics, and is generally considered a subset of CRPS type I.[3]
Cause[edit]
Complex regional pain syndrome is uncommon, and its cause is not clearly understood. CRPS typically develops after an injury, surgery, heart attack, or stroke.[7][11] Investigators estimate that 2–5% of those with peripheral nerve injury,[12] and 13–70% of those with hemiplegia (paralysis of one side of the body)[13] will develop CRPS. In addition, some studies have indicated that cigarette smoking was strikingly present in patients and is statistically linked to RSD. This may be involved in its pathology by enhancing sympathetic activity, vasoconstriction, or by some other unknown neurotransmitter-related mechanism. This hypothesis was based on a retrospective analysis of 53 patients with RSD, which showed that 68% of patients were smokers, compared to only 37% of the control population. The results are preliminary and are limited by their retrospective nature.[14] 7% of people who have CRPS in one limb later develop it in another limb.[15]
Pathophysiology[edit]
Inflammation and alteration of pain perception in the central nervous system are proposed to play important roles. The persistent pain and the perception of nonpainful stimuli as painful are thought to be caused by inflammatory molecules (IL-1, IL-2, TNF-alpha) and neuropeptides (substance P) released from peripheral nerves. This release may be caused by inappropriate cross-talk between sensory and motor fibers at the affected site.[16] CRPS is not a psychological illness, yet pain can cause psychological problems, such as anxiety and depression. Often, impaired social and occupational function occur.[17]
Complex regional pain syndrome is a multifactorial disorder with clinical features of neurogenic inflammation (inflammation mediated by nerve cells), nociceptive sensitisation (which causes extreme sensitivity or allodynia), vasomotor dysfunction (blood flow problems which cause swelling and discolouration) and maladaptive neuroplasticity (where the brain changes and adapts with constant pain signals); CRPS is the result of an "aberrant [inappropriate] response to tissue injury".[6] The "underlying neuronal matrix" of CRPS is seen to involve cognitive and motor as well as nociceptive processing; pinprick stimulation of a CRPS affected limb was painful (mechanical hyperalgesia) and showed a "significantly increased activation" of not just the S1 cortex (contralateral), S2 (bilateral) areas, and insula (bilateral) but also the associative-somatosensory cortices (contralateral), frontal cortices, and parts of the anterior cingulate cortex.[18] In contrast to previous thoughts reflected in the name RSD, it appears that there is reduced sympathetic nervous system outflow, at least in the affected region (although there may be sympatho-afferent coupling).[19] Wind-up (the increased sensation of pain with time)[20] and central nervous system (CNS) sensitization are key neurologic processes that appear to be involved in the induction and maintenance of CRPS.[21]
Compelling evidence shows that the N-methyl-D-aspartate (NMDA) receptor has significant involvement in the CNS sensitization process.[22] It is also hypothesized that elevated CNS glutamate levels promote wind-up and CNS sensitization.[21] In addition, there exists experimental evidence demonstrating the presence of NMDA receptors in peripheral nerves.[23] Because immunological functions can modulate CNS physiology, a variety of immune processes have also been hypothesized to contribute to the initial development and maintenance of peripheral and central sensitization.[24][25] Furthermore, trauma-related cytokine release, exaggerated neurogenic inflammation, sympathetic afferent coupling, adrenoreceptor pathology, glial cell activation, cortical reorganisation,[26] and oxidative damage (e.g., by free radicals) are all factors which have been implicated in the pathophysiology of CRPS.[27] In addition, autoantibodies are present in a wide number of CRPS patients and IgG has been recognized as one of the causes of hypersensitivity that stimulates A and C nociceptors, attributing to the inflammation.[28]
The mechanisms leading to reduced bone mineral density (up to overt osteoporosis) are still unknown. Potential explanations include a dysbalance of the activities of sympathetic and parasympathetic autonomic nervous system[29][30][31] and mild secondary hyperparathyroidism.[32] However, the trigger of secondary hyperparathyroidism has not yet been identified.
In summary, the pathophysiology of complex regional pain syndrome has not yet been defined; CRPS, with its variable manifestations, could be the result of multiple pathophysiological processes.[19]
Prognosis[edit]
The prognosis in CRPS is improved with early and aggressive treatment; with the risk of chronic, debilitating pain being reduced with the early treatment.[65] If treatment is delayed, however, the disorder can quickly spread to the entire limb, and changes in bone, nerve, and muscle may become irreversible. The prognosis is worse with the chronic "cold" form of CRPS and with CRPS affecting the upper extremities.[65] Disuse of the limb after an injury or psychological distress related to an injury are also associated with a poorer prognosis in CRPS.[65] Some cases of CRPS may resolve spontaneously (with 74% of patients in a population-based study in Minnesota undergoing complete resolution of symptoms, often spontaneously), but others may develop chronic pain for many years.[65] Once one is diagnosed with CRPS, should it go into remission, the likelihood of it resurfacing after going into remission is significant. Taking precautions and seeking immediate treatment upon any injury is important.[66]
Epidemiology[edit]
CRPS can occur at any age, with the average age at diagnosis being 42.[12] It affects both men and women; however, CRPS is three times more frequent in females than males.[12]
CRPS affects both adults and children, and the number of reported CRPS cases among adolescents and young adults has been increasing,[67] with a recent observational study finding an incidence of 1.16/100,000 among children in Scotland.[68]
History[edit]
The condition currently known as CRPS was originally described by Ambroise Paré. He successfully treated a severe and persistent pain syndrome that occurred to the French King Charles IX of Valois after a limb phlebotomy [1]. During the American Civil War, Silas Weir Mitchell is sometimes also credited with inventing the name "causalgia".[69] However, this term was actually coined by Mitchell's friend Robley Dunglison from the Greek words for heat and for pain.[70] Contrary to what is commonly accepted, it emerges that these causalgias were certainly major by the importance of the vasomotor and sudomotor symptoms but stemmed from minor neurological lesions. In the 1940s, the term reflex sympathetic dystrophy came into use to describe this condition, based on the theory that sympathetic hyperactivity was involved in the pathophysiology.[71] In 1959, Noordenbos observed in causalgia patients that "the damage of the nerve is always partial."[72] Misuse of the terms, as well as doubts about the underlying pathophysiology, led to calls for better nomenclature. In 1993, a special consensus workshop held in Orlando, Florida, provided the umbrella term "complex regional pain syndrome", with causalgia and RSD as subtypes.[73]
Research[edit]
The National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institutes of Health, supports and conducts research on the brain and central nervous system, including research relevant to RSDS, through grants to major medical institutions across the country. NINDS-supported scientists are working to develop effective treatments for neurological conditions and ultimately, to find ways of preventing them. Investigators are studying new approaches to treat CRPS and intervene more aggressively after traumatic injury to lower the patient's chances of developing the disorder. In addition, NINDS-supported scientists are studying how signals of the sympathetic nervous system cause pain in CRPS patients. Using a technique called microneurography, these investigators are able to record and measure neural activity in single nerve fibers of affected patients. By testing various hypotheses, these researchers hope to discover the unique mechanism that causes the spontaneous pain of CRPS, and that discovery may lead to new ways of blocking pain. Other studies to overcome chronic pain syndromes are discussed in the pamphlet "Chronic Pain: Hope Through Research", published by the NINDS.
Research into treating the condition with mirror visual feedback is being undertaken at the Royal National Hospital for Rheumatic Disease in Bath. Patients are taught how to desensitize in the most effective way, then progress to using mirrors to rewrite the faulty signals in the brain that appear responsible for this condition.[74] However, while CRPS can go into remission, the chance of it reoccurring is significant.
The Netherlands has the most comprehensive program of research into CRPS, as part of a multimillion-Euro initiative called TREND.[75] German and Australian research teams are also pursuing better understanding and treatments for CRPS.[76]