complex regional pain syndrome complex regional pain syndrome complex regional pain syndrome (crps) is any of several painful conditions that are characterized by a continuing (spontaneous and/or evoked) regional pain that is seemingly disproportionate in time or degree to the usual course of any known trauma or other lesion. usually starting in a limb, it 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 people report symptoms throughout their whole bodies. two types exist: reflex sympathetic dystrophy (rsd) and causalgia. having both types is possible. complex regional pain syndromeother namesalgodystrophy; hyponym: reflex sympathetic dystrophy (rsd); hyponym: causalgia; hyponym: reflex neurovascular dystrophy (rnd)leg of an individual (left) with complex regional pain syndrome following tibial bone fracture.specialtyneurology, psychiatry, anesthesiologysymptomspain, hypo- or hyperesthesia, skin temperature abnormalities, parasthesiae, atrophy, stiffnesstreatmentphysical therapy (more effective with early diagnosis); medications (e.g., anticonvulsants, opioids, muscle relaxers, etc.); sympathetic nerve blockade; ketamine infusions; lidocaine infusions; implantable pharmaceuticals; amputationmedicationanticonvulsants (e.g., gabapentin); muscle relaxers (e.g., baclofen), opioids (may be administered orally, via patch, or implanted intrathecal pump); ketamine or lidocaine infusions classification the classification system in use by the international association for the study of pain (iasp) divides crps into two types. it is recognised that people may exhibit both types of crps. international association for the study of pain classification type clinical findings synonyms type i crps without evidence of nerve damage in the affected limb. secondary to injury/trauma. this accounts for about 90% of crps. reflex sympathetic dystrophy, rsd, sudeck's atrophy type ii crps with evidence of nerve damage in the affected limb. causalgia signs and symptoms severe crps of right arm crps visible on hands and wrists 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. the signs and symptoms of crps usually manifest near the injury site. the most common symptoms are extreme pain, including burning, stabbing, grinding, and throbbing. the pain is out of proportion to the severity of the initial injury. moving or touching the limb is often intolerable. patients may develop burning pain and allodynia in either form of crps. both forms of the syndrome are also characterized by autonomic dysfunction, which presents with temperature changes (usually localized, but can be global), cyanosis, and/or edema. the patient may also experience localized swelling; hypersensitivity to nonpainful stimuli such as wind, water, noise, and vibrations; sensitivity to touch (by self, others, and even light clothing or bedding/blankets); abnormally increased sweating (or absent sweating); changes in skin temperature (alternating between overly warm and cold); changes in skin colouring (from white and mottled to bright red or reddish-violet); changes in skin texture (waxy, shiny, thin, tight skin); softening and thinning of bones; arthritis; changes in nails and hair (delayed or increased growth or brittle nails/hair that easily break); muscle spasms; muscle loss (atrophy); tremors; dystonia; allodynia; hyperalgesia; and decreased/restricted ability to or painful movement of the affected body part(s). drop attacks (falls), almost fainting, fainting spells, and visual problems are infrequently reported. the symptoms of crps vary in severity and duration. since crps is a systemic problem, potentially any organ can be affected. symptoms may change over time, and they can vary from person to person. the more dynamic symptoms (especially vascular aspects (edema, temperature) and the location of pain) can change numerous times each day. previously, crps was considered to have three stages, but more recent studies suggest people affected by crps do not progress through sequential stages; the staging system is no longer in wide use. growing evidence instead points toward distinct sub-types of crps. cause complex regional pain syndrome is uncommon, and its cause is not clearly understood. crps typically develops after an injury, surgery, heart attack, or stroke. investigators estimate that 2–5% of those with peripheral nerve injury, and 13-70% of those with hemiplegia (paralysis of one side of the body) 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 and only 37% of controls were smokers. the results are preliminary and are limited by their retrospective nature. 7% of people who have crps in one limb later develop it in another limb. pathophysiology 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, il2, 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. crps is not a psychological illness, yet pain can cause psychological problems, such as anxiety and depression. often, impaired social and occupational function occur. complex regional pain syndrome is a multifactorial disorder with clinical features of neurogenic inflammation (swelling in the central nervous system), 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 response to tissue injury". 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. 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). wind-up (the increased sensation of pain with time) and central nervous system (cns) sensitization are key neurologic processes that appear to be involved in the induction and maintenance of crps. compelling evidence shows that the n-methyl-d-aspartate (nmda) receptor has significant involvement in the cns sensitization process. it is also hypothesized that elevated cns glutamate levels promote wind-up and cns sensitization. in addition, there exists experimental evidence demonstrating the presence of nmda receptors in peripheral nerves. 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. furthermore, trauma-related cytokine release, exaggerated neurogenic inflammation, sympathetic afferent coupling, adrenoreceptor pathology, glial cell activation, cortical reorganisation, and oxidative damage (e.g., by free radicals) are all factors which have been implicated in the pathophysiology of crps. 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. 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 and mild secondary hyperparathyroidism. 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. diagnosis diagnosis is primarily based on clinical findings. the original diagnostic criteria for crps adopted by the international association for the study of pain (iasp) in 1994 have now been superseded in both clinical practice and research by the "budapest criteria" which were created in 2003 and have been found to be more sensitive and specific. they have since been adopted by the iasp. the criteria require there to be pain as well as a history and clinical evidence of sensory, vasomotor, sudomotor, and motor or trophic changes. it is also stated that it is a diagnosis of exclusion. to make a clinical diagnosis all four of the following criteria must be met: continuing pain, which is disproportionate to any inciting event must report at least one symptom in three of the four following categories. sensory: reports of hyperesthesia vasomotor: reports of temperature asymmetry and/or skin color changes and/or skin color asymmetry sudomotor/edema: reports of edema and/or sweating changes and/or sweating asymmetry motor/trophic: reports of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin) must display at least one sign at time of evaluation in two or more of the following categories sensory: evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch and/or temperature sensation and/or deep somatic pressure and/or joint movement) vasomotor: evidence of temperature asymmetry (>1 °c) and/or skin color changes and/or asymmetry sudomotor/edema: evidence of edema and/or sweating changes and/or sweating asymmetry motor/trophic: evidence of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin) there is no other diagnosis that better explains the signs and symptoms diagnostic adjuncts no specific test is available for crps, which is diagnosed primarily through observation of the symptoms. however, thermography, sweat testing, x-rays, electrodiagnostics, and sympathetic blocks can be used to build up a picture of the disorder. diagnosis is complicated by the fact that some patients improve without treatment. a delay in diagnosis and/or treatment for this syndrome can result in severe physical and psychological problems. early recognition and prompt treatment provide the greatest opportunity for recovery. thermography presently, established empirical evidence suggests against thermography's efficacy as a reliable tool for diagnosing crps. although crps may, in some cases, lead to measurably altered blood flow throughout an affected region, many other factors can also contribute to an altered thermographic reading, including the patient's smoking habits, use of certain skin lotions, recent physical activity, and prior history of trauma to the region. also, not all patients diagnosed with crps demonstrate such "vasomotor instability" — particularly those in the later stages of the disease. 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. in order to minimise the confounding influence of external factors, patients undergoing infrared thermographic testing must conform to special restrictions regarding the use of certain vasoconstrictors (namely, nicotine and caffeine), skin lotions, physical therapy, and other diagnostic procedures in the days prior to testing. patients may also be required to discontinue certain pain medications and sympathetic blockers. 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. a technician then takes infrared images of both the patient's affected and unaffected limbs, as well as reference images of other parts of the patient's body, including his or her face, upper back, and lower back. 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. in a normal, intact, functioning autonomic nervous system, a patient's affected extremity will become colder. conversely, warming of an affected extremity may indicate a disruption of the body's normal thermoregulatory vasoconstrictor function, which may sometimes indicate underlying crps. radiography scintigraphy, plain radiographs, and magnetic resonance imaging may all be useful diagnostically. patchy osteoporosis (post-traumatic osteoporosis), which may be due to disuse of the affected extremity, can be detected through x-ray imagery as early as two weeks after the onset of crps. a bone scan of the affected limb may detect these changes even sooner and can almost confirm the disease. bone densitometry can also be used to detect changes in bone mineral density. it can also be used to monitor the results of treatment since bone densitometry parameters improve with treatment. ultrasound ultrasound-based osteodensitometry (ultrasonometry) may be potential future radiation-free