Complex regional pain syndrome (CRPS type 1 and type 2), sometimes referred to by the hyponyms reflex sympathetic dystrophy (RSD) or reflex neurovascular dystrophy (RND), is a rare and severe form of neuroinflammatory and dysautonomic disorder causing chronic pain, neurovascular, and neuropathic symptoms.

Although it can vary widely, the classic presentation occurs when severe pain from a physical trauma or neurotropic viral infection[1] outlasts the expected recovery time, and may subsequently spread to uninjured areas.

Usually starting in a single limb, CRPS often first manifests as pain, swelling, limited range of motion or partial paralysis, and/or changes to the skin and bones.

[4] The classification system in use by the International Association for the Study of Pain (IASP) divides CRPS into two types based on the presence or absence of measurable nerve pathophysiology.

[5][6] Clinical features of CRPS have been found to be inflammation resulting from the release of certain pro-inflammatory chemical signals from surrounding nerve cells; hypersensitization of pain receptors; dysfunction of local vasoconstriction and vasodilation; and maladaptive neuroplasticity.

[18] 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".

[7] 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.

[19] 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).

[20] Wind-up (the increased sensation of pain with time)[21] and central nervous system (CNS) sensitization are key neurologic processes that appear to be involved in the induction and maintenance of CRPS.

[24] 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.

[25][26] Furthermore, trauma-related cytokine release, exaggerated neurogenic inflammation, sympathetic afferent coupling, adrenoreceptor pathology, glial cell activation, cortical reorganisation,[27] and oxidative damage (e.g., by free radicals) are all factors which have been implicated in the pathophysiology of CRPS.

[28] 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.

Potential explanations include a dysbalance of the activities of sympathetic and parasympathetic autonomic nervous system[30][31][32] and mild secondary hyperparathyroidism.

[citation needed] Presently, established empirical evidence suggests against thermography's efficacy as a reliable tool for diagnosing CRPS.

[37] Thus, thermography alone cannot be used as conclusive evidence for—or against—a diagnosis of CRPS and must be interpreted in light of the patient's larger medical history and prior diagnostic studies.

After a patient arrives at a thermographic laboratory, he or she is allowed to reach thermal equilibrium in a 16–20 °C, draft-free, steady-state room wearing a loose fitting cotton hospital gown for approximately twenty minutes.

After capturing a set of baseline images, some labs further require the patient to undergo cold-water autonomic-functional-stress-testing to evaluate the function of their autonomic nervous system's peripheral vasoconstrictor reflex.

This is performed by placing a patient's unaffected limb in a cold water bath (approximately 20 °C) for five minutes while collecting images.

[citation needed] Ultrasound-based osteodensitometry (ultrasonometry) may be potential future radiation-free technique to identify reduced bone mineral density in CRPS.

These drugs must be prescribed and monitored under close supervision of a physician as they can quickly lead to physical dependence and addiction.

[60] Although they improve patient pain and quality of life, evidence is unclear regarding effects on mental health and general functioning.

[62] Surgical, chemical, or radiofrequency sympathectomy—interruption of the affected portion of the sympathetic nervous system—can be used as a last resort in patients with impending tissue loss, edema, recurrent infection, or ischemic necrosis.

[66] Some cases of CRPS may resolve spontaneously, with 74% of patients in a Minnesota study experiencing complete symptom resolution, while others may have chronic or relapsing-and-remitting disease.

[69] The condition currently known as CRPS was originally described by Ambroise Paré, who treated a severe and persistent pain syndrome suffered by Charles IX of France after a limb phlebotomy.

In 1993, a special consensus workshop held in Orlando, Florida, provided the umbrella term "complex regional pain syndrome", with causalgia and reflex sympathetic dystrophy as subtypes.

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.

Using a technique called microneurography, these investigators are able to record and measure neural activity in single nerve fibers of affected patients.

[citation needed] 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.

[citation needed] The Netherlands has the most comprehensive program of research into CRPS, as part of a multimillion-Euro initiative called TREND.