:Complex regional pain syndrome

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.{{cite journal | year=1970 | last1=Young-Do | first1=K |title=Diagnosis of complex regional pain syndrome | journal=Annals of Clinical Neurophysiology | volume=24 | issue=2 | pages=35–45 | doi=10.14253/acn.2022.24.2.35 | s2cid=253273786 | doi-access=free }}{{cite journal | pmid=33729210 | year=2021 | last1=Goebel | first1=A | last2=Birklein | first2=F | last3=Brunner | first3=F | last4=Clark | first4=JD | last5=Gierthmühlen | first5=J | last6=Harden | first6=N | last7=Huygen | first7=F | last8=Knudsen | first8=L | last9=McCabe | first9=C | last10=Lewis | first10=J | last11=Maihöfner | first11=C | last12=Magerl | first12=W | last13=Moseley | first13=GL | last14=Terkelsen | first14=A | last15=Thomassen | first15=I | last16=Bruehl | first16=S | title=The Valencia consensus-based adaptation of the IASP complex regional pain syndrome diagnostic criteria | journal=Pain | volume=162 | issue=9 | pages=2346–2348 | doi=10.1097/j.pain.0000000000002245 | pmc=8374712 | s2cid=232263568 }}

File:Severe CRPS.jpg

File:CRPS 002ms5.jpg

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.{{cite web|url=https://www.mayoclinic.org/diseases-conditions/complex-regional-pain-syndrome/symptoms-causes/syc-20371151|title=Complex regional pain syndrome - Symptoms and causes|website=Mayo Clinic}} Moving or touching the limb is disproportionately painful (allodynia). Other findings are aspects of disuse including swelling, stiffness (limited range of motion), and disuse related changes to the skin (temperature, color, sweating, texture) and bones (disuse osteoporosis).{{cite journal | vauthors = Taylor SS, Noor N, Urits I, Paladini A, Sadhu MS, Gibb C, Carlson T, Myrcik D, Varrassi G, Viswanath O | display-authors = 6 | title = Complex Regional Pain Syndrome: A Comprehensive Review | journal = Pain and Therapy | volume = 10 | issue = 2 | pages = 875–892 | date = December 2021 | pmid = 34165690 | pmc = 8586273 | doi = 10.1007/s40122-021-00279-4 | publication-date = 24 June 2021 }}{{cite journal | pmid=33738515 | year=2022 | last1=Rolvien | first1=T | last2=Amling | first2=M | title=Disuse Osteoporosis: Clinical and Mechanistic Insights | journal=Calcif Tissue Int | volume=110 | issue=5 | pages=592–604 | doi=10.1007/s00223-021-00836-1 | s2cid=232304611 | doi-access=free | pmc=9013332 }}

A prior concept of CRPS having three stages is no longer in wide use.{{cite journal | vauthors = Bruehl S, Harden RN, Galer BS, Saltz S, Backonja M, Stanton-Hicks M | title = Complex regional pain syndrome: are there distinct subtypes and sequential stages of the syndrome? | journal = Pain | volume = 95 | issue = 1–2 | pages = 119–124 | date = January 2002 | pmid = 11790474 | doi = 10.1016/s0304-3959(01)00387-6 | s2cid = 20773804 }} The trend is now to consider distinct sub-types of CRPS.

Complex regional pain syndrome is uncommon, and its cause is unclear. CRPS typically develops after an injury, surgery, heart attack, or stroke.{{cite web|url=http://www.nhs.uk/Conditions/Complex-Regional-Pain-Syndrome/Pages/Introduction.aspx|title=Complex regional pain syndrome|date=2017-10-19|website=nhs.uk}} 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){{cite journal | vauthors = Yu D | title = Shoulder pain in hemiplegia | journal = Physical Medicine and Rehabilitation Clinics of North America | volume = 15 | issue = 3 | pages = vi–vii, 683–97 | date = August 2004 | pmid = 15219895 | doi = 10.1016/S1047-9651(03)00130-X }} will develop CRPS. In addition, some studies{{cn|date=April 2025}} have indicated that tobacco smoking is more often present in CRPS patients. Smoking may be involved in its pathophysiology among tobacco users by enhancing sympathetic activity, vasoconstriction, or other unknown neurotransmitter-related mechanism.{{cn|date=April 2025}} This hypothesis was based on a small 1993 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.{{cite journal | vauthors = Pawelka S, Fialka V, Ernst E | title = Reflex sympathetic dystrophy and cigarette smoking | journal = The Journal of Hand Surgery | volume = 18 | issue = 1 | pages = 168–169 | date = January 1993 | pmid = 8423309 | doi = 10.1016/0363-5023(93)90273-6 }} A minority (7%) of individuals with CRPS in a single limb go on to develop it in another.{{cite book | vauthors = Goebel A, Turner-Stokes LF | title = Complex regional pain syndrome in adults: UK guidelines for diagnosis, referral and management in primary and secondary care. | publisher = Royal College of Physicians London | date = May 2012 }}

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.{{cite journal | vauthors = Bussa M, Guttilla D, Lucia M, Mascaro A, Rinaldi S | title = Complex regional pain syndrome type I: a comprehensive review | journal = Acta Anaesthesiologica Scandinavica | volume = 59 | issue = 6 | pages = 685–697 | date = July 2015 | pmid = 25903457 | doi = 10.1111/aas.12489 | s2cid = 20134091 }} CRPS is not a psychological illness, yet pain can cause psychological problems, such as anxiety and depression. Often, impaired social and occupational function occur.{{cite journal | vauthors = Lohnberg JA, Altmaier EM | title = A review of psychosocial factors in complex regional pain syndrome | journal = Journal of Clinical Psychology in Medical Settings | volume = 20 | issue = 2 | pages = 247–254 | date = June 2013 | pmid = 22961122 | doi = 10.1007/s10880-012-9322-3 | s2cid = 14756892 }}

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".{{cite journal | vauthors = Marinus J, Moseley GL, Birklein F, Baron R, Maihöfner C, Kingery WS, van Hilten JJ | title = Clinical features and pathophysiology of complex regional pain syndrome | journal = The Lancet. Neurology | volume = 10 | issue = 7 | pages = 637–648 | date = July 2011 | pmid = 21683929 | pmc = 5511749 | doi = 10.1016/S1474-4422(11)70106-5 }} 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.{{cite journal | vauthors = Maihöfner C, Forster C, Birklein F, Neundörfer B, Handwerker HO | title = Brain processing during mechanical hyperalgesia in complex regional pain syndrome: a functional MRI study | journal = Pain | volume = 114 | issue = 1–2 | pages = 93–103 | date = March 2005 | pmid = 15733635 | doi = 10.1016/j.pain.2004.12.001 | s2cid = 19187294 }} 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).{{cite book | vauthors = Howard W | chapter = Complex regional pain syndrome (CRPS), a brief review | pages = 1–6 | title = Australasian anaesthesia 2011: invited papers and selected continuing education lectures |date=2012 |publisher=Australian and New Zealand College of Anaesthetists |location=Melbourne, Vic. |isbn=978-0-9775174-7-3 | chapter-url = http://www.qld.anzca.edu.au/anzca/resources/college-publications/pdfs/ANZCA%20Blue%20Book%202011%20P9.pdf#page=10 | archive-url = https://web.archive.org/web/20150203114743/https://www.qld.anzca.edu.au/anzca/resources/college-publications/pdfs/ANZCA%20Blue%20Book%202011%20P9.pdf | archive-date = 3 February 2015 }} Wind-up (the increased sensation of pain with time){{cite web|url=http://courses.washington.edu/conj/sensory/pain.htm | archive-url = https://web.archive.org/web/20050214075318/http://courses.washington.edu/conj/sensory/pain.htm | archive-date = 14 February 2005 |title=Pain | work = Courses.washington.edu |access-date=2013-12-23 | publisher = University of Washington }} and central nervous system (CNS) sensitization are key neurologic processes that appear to be involved in the induction and maintenance of CRPS.{{cite journal | vauthors = Correll GE, Maleki J, Gracely EJ, Muir JJ, Harbut RE | title = Subanesthetic ketamine infusion therapy: a retrospective analysis of a novel therapeutic approach to complex regional pain syndrome | journal = Pain Medicine | volume = 5 | issue = 3 | pages = 263–275 | date = September 2004 | pmid = 15367304 | doi = 10.1111/j.1526-4637.2004.04043.x | doi-access = free }}

Compelling evidence shows that the N-methyl-D-aspartate (NMDA) receptor has significant involvement in the CNS sensitization process.{{cite journal | vauthors = Kiefer RT, Rohr P, Ploppa A, Nohé B, Dieterich HJ, Grothusen J, Altemeyer KH, Unertl K, Schwartzman RJ | display-authors = 6 | title = A pilot open-label study of the efficacy of subanesthetic isomeric S(+)-ketamine in refractory CRPS patients | journal = Pain Medicine | volume = 9 | issue = 1 | pages = 44–54 | year = 2008 | pmid = 18254766 | doi = 10.1111/j.1526-4637.2006.00223.x | doi-access = free }}

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.{{cite journal | vauthors = Pöyhiä R, Vainio A | title = Topically administered ketamine reduces capsaicin-evoked mechanical hyperalgesia | journal = The Clinical Journal of Pain | volume = 22 | issue = 1 | pages = 32–36 | date = January 2006 | pmid = 16340591 | doi = 10.1097/01.ajp.0000149800.39240.95 | s2cid = 14035667 }} 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.{{cite journal | vauthors = Watkins LR, Maier SF | title = Immune regulation of central nervous system functions: from sickness responses to pathological pain | journal = Journal of Internal Medicine | volume = 257 | issue = 2 | pages = 139–155 | date = February 2005 | pmid = 15656873 | doi = 10.1111/j.1365-2796.2004.01443.x | s2cid = 24853745 | doi-access = free }}{{cite journal | vauthors = Koffler SP, Hampstead BM, Irani F, Tinker J, Kiefer RT, Rohr P, Schwartzman RJ | title = The neurocognitive effects of 5 day anesthetic ketamine for the treatment of refractory complex regional pain syndrome | journal = Archives of Clinical Neuropsychology | volume = 22 | issue = 6 | pages = 719–729 | date = August 2007 | pmid = 17611073 | doi = 10.1016/j.acn.2007.05.005 | doi-access = free }} Furthermore, trauma-related cytokine release, exaggerated neurogenic inflammation, sympathetic afferent coupling, adrenoreceptor pathology, glial cell activation, cortical reorganisation,{{cite journal | vauthors = Birklein F | title = Complex regional pain syndrome | journal = Journal of Neurology | volume = 252 | issue = 2 | pages = 131–138 | date = February 2005 | pmid = 15729516 | doi = 10.1007/s00415-005-0737-8 | s2cid = 2965351 | citeseerx = 10.1.1.483.1324 }} and oxidative damage (e.g., by free radicals) are all factors which have been implicated in the pathophysiology of CRPS.{{cite journal | vauthors = Zollinger PE, Tuinebreijer WE, Breederveld RS, Kreis RW | title = Can vitamin C prevent complex regional pain syndrome in patients with wrist fractures? A randomized, controlled, multicenter dose-response study | journal = The Journal of Bone and Joint Surgery. American Volume | volume = 89 | issue = 7 | pages = 1424–1431 | date = July 2007 | pmid = 17606778 | doi = 10.2106/JBJS.F.01147 | s2cid = 7200059 }} 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.{{cite journal | vauthors = Cuhadar U, Gentry C, Vastani N, Sensi S, Bevan S, Goebel A, Andersson DA | title = Autoantibodies produce pain in complex regional pain syndrome by sensitizing nociceptors | journal = Pain | volume = 160 | issue = 12 | pages = 2855–2865 | date = December 2019 | pmid = 31343542 | doi = 10.1097/j.pain.0000000000001662 | doi-access = free }}

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{{cite journal | vauthors = Bajayo A, Bar A, Denes A, Bachar M, Kram V, Attar-Namdar M, Zallone A, Kovács KJ, Yirmiya R, Bab I | display-authors = 6 | title = Skeletal parasympathetic innervation communicates central IL-1 signals regulating bone mass accrual | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 38 | pages = 15455–15460 | date = September 2012 | pmid = 22949675 | pmc = 3458367 | doi = 10.1073/pnas.1206061109 | doi-access = free | bibcode = 2012PNAS..10915455B }}{{cite journal | vauthors = Kondo H, Takeuchi S, Togari A | title = β-Adrenergic signaling stimulates osteoclastogenesis via reactive oxygen species | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 304 | issue = 5 | pages = E507–E515 | date = March 2013 | pmid = 23169789 | doi = 10.1152/ajpendo.00191.2012 }}{{cite journal | vauthors = Nencini S, Ivanusic JJ | title = The Physiology of Bone Pain. How Much Do We Really Know? | journal = Frontiers in Physiology | volume = 7 | pages = 157 | date = 2016 | pmid = 27199772 | pmc = 4844598 | doi = 10.3389/fphys.2016.00157 | doi-access = free }} and mild secondary hyperparathyroidism.{{cite journal | vauthors = Bazika-Gerasch B, Maier C, Kumowski N, Fiege C, Kaisler M, Vollert J, Dietrich JW | title = Compared to limb pain of other origin, ultrasonographic osteodensitometry reveals loss of bone density in complex regional pain syndrome | journal = Pain | volume = 160 | issue = 6 | pages = 1261–1269 | date = June 2019 | pmid = 30747906 | doi = 10.1097/j.pain.0000000000001520 | s2cid = 73428940 }} However, the trigger of secondary hyperparathyroidism has not yet been identified.{{citation needed|date=October 2020}}

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 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.{{cite journal | vauthors = Harden NR, Bruehl S, Perez RS, Birklein F, Marinus J, Maihofner C, Lubenow T, Buvanendran A, Mackey S, Graciosa J, Mogilevski M, Ramsden C, Chont M, Vatine JJ | display-authors = 6 | title = Validation of proposed diagnostic criteria (the "Budapest Criteria") for Complex Regional Pain Syndrome | journal = Pain | volume = 150 | issue = 2 | pages = 268–274 | date = August 2010 | pmid = 20493633 | pmc = 2914601 | doi = 10.1016/j.pain.2010.04.030 }} 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.{{Cite book| vauthors = Frontera WR, Silver JK, Rizzo TD |url=https://books.google.com/books?id=1sXsAwAAQBAJ&q=Motor+or+Trophic+changes.+It+is+also+stated+that+it+is+a+diagnosis+of+exclusion.&pg=PA497|title=Essentials of Physical Medicine and Rehabilitation E-Book|date=2014-09-05|publisher=Elsevier Health Sciences|isbn=978-0-323-22272-3|language=en}}

To make a clinical diagnosis all four of the following criteria must be met:{{cite journal | vauthors = Harden NR, Bruehl S, Perez RS, Birklein F, Marinus J, Maihofner C, Lubenow T, Buvanendran A, Mackey S, Graciosa J, Mogilevski M, Ramsden C, Chont M, Vatine JJ | display-authors = 6 | title = Validation of proposed diagnostic criteria (the "Budapest Criteria") for Complex Regional Pain Syndrome | journal = Pain | volume = 150 | issue = 2 | pages = 268–274 | date = August 2010 | pmid = 20493633 | pmc = 2914601 | doi = 10.1016/j.pain.2010.04.030 | s2cid = 30417585 }}

1. Continuing pain, which is disproportionate to any inciting event
2. Must report at least one symptom in three of the four following categories.
3. * Sensory: Reports of hyperesthesia
4. * Vasomotor: Reports of temperature asymmetry and/or skin color changes and/or skin color asymmetry
5. * Sudomotor/Edema: Reports of edema and/or sweating changes and/or sweating asymmetry
6. * Motor/Trophic: Reports of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)
7. Must display at least one sign at time of evaluation in two or more of the following categories
8. * 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)
9. * Vasomotor: Evidence of temperature asymmetry (>{{convert|1|C-change}}) and/or skin color changes and/or asymmetry
10. * Sudomotor/Edema: Evidence of edema and/or sweating changes and/or sweating asymmetry
11. * Motor/Trophic: Evidence of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)
12. There is no other diagnosis that better explains the signs and symptoms

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.{{citation needed|date=October 2020}}

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.{{cite journal | vauthors = Birklein F, Künzel W, Sieweke N | title = Despite clinical similarities there are significant differences between acute limb trauma and complex regional pain syndrome I (CRPS I) | journal = Pain | volume = 93 | issue = 2 | pages = 165–171 | date = August 2001 | pmid = 11427328 | doi = 10.1016/s0304-3959(01)00309-8 | s2cid = 20172363 }}

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.{{cite journal | vauthors = Wasner G, Schattschneider J, Baron R | title = Skin temperature side differences--a diagnostic tool for CRPS? | journal = Pain | volume = 98 | issue = 1–2 | pages = 19–26 | date = July 2002 | pmid = 12098613 | doi = 10.1016/s0304-3959(01)00470-5 | s2cid = 24474769 }}

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 {{convert|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 {{convert|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.{{cite journal | vauthors = Gulevich SJ, Conwell TD, Lane J, Lockwood B, Schwettmann RS, Rosenberg N, Goldman LB | title = Stress infrared telethermography is useful in the diagnosis of complex regional pain syndrome, type I (formerly reflex sympathetic dystrophy) | journal = The Clinical Journal of Pain | volume = 13 | issue = 1 | pages = 50–59 | date = March 1997 | pmid = 9084952 | doi = 10.1097/00002508-199703000-00008 | s2cid = 21310682 }}

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.{{citation needed|date=December 2020}}

Ultrasound-based osteodensitometry (ultrasonometry) may be potential future radiation-free technique to identify reduced bone mineral density in CRPS. Additionally, this method promises to quantify the bone architecture in the periphery of affected limbs. This method is still under experimental development.{{citation needed|date=October 2020}}

Electromyography (EMG) and nerve conduction studies (NCS) are important ancillary tests in CRPS because they are among the most reliable methods of detecting nerve injury. They can be used as one of the primary methods to distinguish between CRPS types I and II, which differ based on evidence of actual nerve damage. EMG and NCS are also among the best tests for ruling in or out alternative diagnoses. CRPS is a "diagnosis of exclusion", which requires that no other diagnosis can explain the patient's symptoms. This is very important to emphasise because patients otherwise can be given a wrong diagnosis of CRPS when they actually have a treatable condition that better accounts for their symptoms. An example is severe carpal tunnel syndrome (CTS), which can often present in a very similar way to CRPS. Unlike CRPS, CTS can often be corrected with surgery to alleviate the pain and avoid permanent nerve damage and malformation.{{cite web |url=http://www.rsdfoundation.org/en/en_clinical_practice_guidelines.html |title=Reflex Sympathetic Dystrophy Clinical Practice Guidelines |publisher=Rsdfoundation.org |date=2003-01-01 |access-date=2013-12-23 |url-status=dead |archive-url=https://web.archive.org/web/20131102061837/http://www.rsdfoundation.org/en/en_clinical_practice_guidelines.html |archive-date=2013-11-02 }}

Both EMG and NCS involve some measure of discomfort. EMG involves the use of a tiny needle inserted into specific muscles to test the associated muscle and nerve function. Both EMG and NCS involve very mild shocks that in normal patients are comparable to a rubber band snapping on the skin. Although these tests can be very useful in CRPS, thorough informed consent must be obtained prior to the procedure, particularly in patients experiencing severe allodynia. In spite of the utility of the test, these patients may wish to decline the procedure to avoid discomfort.{{citation needed|date=October 2020}}

• Type I, formerly known as reflex sympathetic dystrophy (RSD), Sudeck's atrophy, or algoneurodystrophy, does not exhibit demonstrable nerve lesions. As the vast majority of patients diagnosed with CRPS have this type, it is most commonly referred to in medical literature as type I.{{citation needed|date=December 2020}}
• Type II, formerly known as causalgia, has evidence of obvious nerve damage. Despite evidence of nerve injury, the cause or the mechanisms of CRPS type II are as unknown, as the mechanisms of type I.{{citation needed|date=December 2020}}

Patients are frequently classified into two groups based upon temperature: "warm" or "hot" CRPS in one group and "cold" CRPS in the other group. The majority of patients (about 70%) have the "hot" type, which is said to be an acute form of CRPS.{{cite journal |vauthors=Eberle T, Doganci B, Krämer HH |title=Warm and cold complex regional pain syndromes: differences beyond skin temperature? |journal=Neurology |volume=72 |issue=6 |pages=505–12 |date=February 2009 |pmid=19204260 |doi=10.1212/01.wnl.0000341930.35494.66|s2cid=6670243 }} Cold CRPS is said to be indicative of a more chronic CRPS and is associated with poorer McGill Pain Questionnaire scores, increased central nervous system reorganisation, and a higher prevalence of dystonia. Prognosis is not favourable for cold CRPS patients; longitudinal studies suggest these patients have "poorer clinical pain outcomes and show persistent signs of central sensitisation correlating with disease progression".{{cite journal |vauthors=Vaneker M, Wilder-Smith OH, Schrombges P, de Man-Hermsen I, Oerlemans HM |title=Patients initially diagnosed as "warm" or "cold" CRPS 1 show differences in central sensory processing some eight years after diagnosis: a quantitative sensory testing study |journal=Pain |volume=115 |issue=1–2 |pages=204–11 |date=May 2005 |pmid=15836983 |doi=10.1016/j.pain.2005.02.031|s2cid=11529390 }}

Vitamin C supplementation may be useful in prevention of the syndrome following fracture of the forearm, foot, or ankle.{{cite journal | vauthors = Meena S, Sharma P, Gangary SK, Chowdhury B | title = Role of vitamin C in prevention of complex regional pain syndrome after distal radius fractures: a meta-analysis | journal = European Journal of Orthopaedic Surgery & Traumatology | volume = 25 | issue = 4 | pages = 637–641 | date = May 2015 | pmid = 25488053 | doi = 10.1007/s00590-014-1573-2 | s2cid = 22016034 }}

Treatment of CRPS often involves a number of modalities.{{cite journal |vauthors=Shah A, Kirchner JS |title=Complex regional pain syndrome |journal=Foot and Ankle Clinics |volume=16 |issue=2 |pages=351–66 |date=June 2011 |pmid=21600455 |doi=10.1016/j.fcl.2011.03.001|citeseerx=10.1.1.483.1324 }}

Physical and occupational therapy have low-quality evidence to support their use.{{Cite journal |last1=Ferraro |first1=Michael C. |last2=Cashin |first2=Aidan G. |last3=Wand |first3=Benedict M. |last4=Smart |first4=Keith M. |last5=Berryman |first5=Carolyn |last6=Marston |first6=Louise |last7=Moseley |first7=G. Lorimer |last8=McAuley |first8=James H. |last9=O'Connell |first9=Neil E. |date=2023-06-12 |title=Interventions for treating pain and disability in adults with complex regional pain syndrome- an overview of systematic reviews |url= |journal=The Cochrane Database of Systematic Reviews |volume=2023 |issue=6 |pages=CD009416 |doi=10.1002/14651858.CD009416.pub3 |issn=1469-493X |pmc=10259367 |pmid=37306570 }} Physical therapy interventions may include transcutaneous electrical nerve stimulation, progressive weight bearing, graded tactile desensitization, massage, and contrast bath therapy. In a retrospective cohort (unblinded, non-randomized, and with intention-to-treat) of fifty patients diagnosed with CRPS, patients' subjective pain and body perception scores decreased after engagement with a two-week multidisciplinary rehabilitation program. The authors call for randomized controlled trials to probe the true value of interdisciplinary programs for CRPS patients.{{cite journal | vauthors = Lewis JS, Kellett S, McCullough R, Tapper A, Tyler C, Viner M, Palmer S | title = Body Perception Disturbance and Pain Reduction in Longstanding Complex Regional Pain Syndrome Following a Multidisciplinary Rehabilitation Program | journal = Pain Medicine | volume = 20 | issue = 11 | pages = 2213–2219 | date = November 2019 | pmid = 31373373 | doi = 10.1093/pm/pnz176 }}

Mirror box therapy uses a mirror box, or a stand-alone mirror, to reflect the normal limb so that the patient thinks they are looking at the affected limb. Movement of this reflected normal limb is then performed so that it seems to the patient as though they are performing movement with the affected limb. Mirror box therapy appears to be beneficial at least in early CRPS.{{cite journal |vauthors=O'Connell NE, Wand BM, McAuley J, Marston L, Moseley GL |date=April 2013 |title=Interventions for treating pain and disability in adults with complex regional pain syndrome |journal=The Cochrane Database of Systematic Reviews |volume=2013 |issue=4 |pages=CD009416 |doi=10.1002/14651858.CD009416.pub2 |pmc=6469537 |pmid=23633371}} However, the beneficial effects of mirror therapy in the long term are still unproven.{{cite journal | vauthors = Moseley LG, Zalucki NM, Wiech K | title = Tactile discrimination, but not tactile stimulation alone, reduces chronic limb pain | journal = Pain | volume = 137 | issue = 3 | pages = 600–608 | date = July 2008 | pmid = 18054437 | doi = 10.1016/j.pain.2007.10.021 | s2cid = 2757963 }}

Graded motor imagery appears to be useful for people with CRPS-1.{{cite journal |vauthors=Daly AE, Bialocerkowski AE |title=Does evidence support physiotherapy management of adult Complex Regional Pain Syndrome Type One? A systematic review |journal=European Journal of Pain |volume=13 |issue=4 |pages=339–53 |date=April 2009 |pmid=18619873 |doi=10.1016/j.ejpain.2008.05.003|s2cid=207607466 }} Graded motor imagery is a sequential process that consists of (a) laterality reconstruction, (b) motor imagery, and (c) mirror therapy.{{cite web |url=http://www.gradedmotorimagery.com/ |title=Graded Motor Imagery |publisher=Graded Motor Imagery |access-date=2013-12-23 |archive-date=2014-01-02 |archive-url=https://web.archive.org/web/20140102194808/http://gradedmotorimagery.com/ |url-status=dead }}

Transcutaneous Electrical Nerve Stimulation (TENS)

Transcutaneous Electrical Nerve Stimulation (TENS) is a therapy that uses low-voltage electrical signals to provide pain relief through electrodes that are placed on the surface of the skin. Evidence supports its use in treating pain and edema associated with CRPS, but it does not seem to increase functional ability in CRPS patients.{{cite journal | vauthors = Duong S, Bravo D, Todd KJ, Finlayson RJ, Tran Q | title = Treatment of complex regional pain syndrome: an updated systematic review and narrative synthesis | journal = Canadian Journal of Anaesthesia | volume = 65 | issue = 6 | pages = 658–684 | date = June 2018 | pmid = 29492826 | doi = 10.1007/s12630-018-1091-5 | doi-access = free }}

Tentative evidence supports the use of bisphosphonates, calcitonin, and ketamine.{{cite journal | vauthors = Harden RN, Oaklander AL, Burton AW, Perez RS, Richardson K, Swan M, Barthel J, Costa B, Graciosa JR, Bruehl S | display-authors = 6 | title = Complex regional pain syndrome: practical diagnostic and treatment guidelines, 4th edition | journal = Pain Medicine | volume = 14 | issue = 2 | pages = 180–229 | date = February 2013 | pmid = 23331950 | doi = 10.1111/pme.12033 | doi-access = free }} Nerve blocks with guanethidine appear to be harmful. Evidence for sympathetic nerve blocks generally is insufficient to support their use.{{cite journal | vauthors = O'Connell NE, Wand BM, Gibson W, Carr DB, Birklein F, Stanton TR | title = Local anaesthetic sympathetic blockade for complex regional pain syndrome | journal = The Cochrane Database of Systematic Reviews | volume = 7 | issue = 7 | pages = CD004598 | date = July 2016 | pmid = 27467116 | pmc = 7202132 | doi = 10.1002/14651858.CD004598.pub4 | type = Submitted manuscript }} Intramuscular botulinum injections may benefit people with symptoms localized to one extremity.{{cite journal | vauthors = Kharkar S, Ambady P, Venkatesh Y, Schwartzman RJ | title = Intramuscular botulinum toxin in complex regional pain syndrome: case series and literature review | journal = Pain Physician | volume = 14 | issue = 5 | pages = 419–424 | year = 2011 | pmid = 21927045 | url = http://www.painphysicianjournal.com/linkout_vw.php?issn=1533-3159&vol=14&page=419 | url-status = dead | archive-url = https://web.archive.org/web/20150203120213/http://www.painphysicianjournal.com/linkout_vw.php?issn=1533-3159&vol=14&page=419 | archive-date = 2015-02-03 }}

Ketamine, a dissociative anesthetic, appears promising as a treatment for CRPS.{{cite journal | vauthors = Azari P, Lindsay DR, Briones D, Clarke C, Buchheit T, Pyati S | title = Efficacy and safety of ketamine in patients with complex regional pain syndrome: a systematic review | journal = CNS Drugs | volume = 26 | issue = 3 | pages = 215–228 | date = March 2012 | pmid = 22136149 | doi = 10.2165/11595200-000000000-00000 | s2cid = 26780542 }} It may be used in low doses if other treatments have not worked.{{cite journal | vauthors = Schwartzman RJ, Alexander GM, Grothusen JR | title = The use of ketamine in complex regional pain syndrome: possible mechanisms | journal = Expert Review of Neurotherapeutics | volume = 11 | issue = 5 | pages = 719–734 | date = May 2011 | pmid = 21539489 | doi = 10.1586/ern.11.31 | s2cid = 18063794 }}{{cite journal | vauthors = Niesters M, Martini C, Dahan A | title = Ketamine for chronic pain: risks and benefits | journal = British Journal of Clinical Pharmacology | volume = 77 | issue = 2 | pages = 357–367 | date = February 2014 | pmid = 23432384 | pmc = 4014022 | doi = 10.1111/bcp.12094 }} No benefit on either function or depression, however, has been seen.

As of 2013, high-quality evidence supports the use of bisphosphonates (either orally or via IV infusion) in the treatment of CRPS. Bisphosphonates inhibit osteoclasts: cells involved in the resorption of bone. Bone remodeling (via osteoclast activity in bone resorption) is sometimes thought to be hyperactive in CRPS. It is hypothesized that bone resorption causes acidification of the intercellular milieu, which, in turn, activates nerves involved in nociception that densely innervate bone and cause pain. Therefore, inhibiting bone resorption and remodeling is thought to help with regard to CRPS pain. CRPS involving high levels of bone resorption, as seen on bone scan, is more likely to respond to bisphosphonate therapy.

Opioids such as oxycodone, morphine, hydrocodone, and fentanyl have a controversial place in the treatment of CRPS. These drugs must be prescribed and monitored under close supervision of a physician as they can quickly lead to physical dependence and addiction.{{Cite web | url=https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Complex-Regional-Pain-Syndrome-Fact-Sheet | title=Complex Regional Pain Syndrome Fact Sheet | work = National Institute of Neurological Disorders and Stroke }} To date so far, no long-term studies of oral opioid use in treating neuropathic pain, including CRPS, have been performed. The consensus among experts is that opioids should not be a first-line therapy and should be considered only after all other modalities (e.g., non-opioid medications, physical therapy, and procedures) have been trialed.{{cite journal| vauthors = Stengel M, Binder A, Baron R |title=Update on the diagnosis and management of complex regional pain syndrome|journal=Adv Pain Manage.|date=2007|volume=3|issue=1|pages=96–104}}

Spinal cord stimulation appears to be an effective therapy in the management of patients with CRPS type I (level A evidence) and type II (level D evidence).{{cite journal | vauthors = Taylor RS, Van Buyten JP, Buchser E | title = Spinal cord stimulation for complex regional pain syndrome: a systematic review of the clinical and cost-effectiveness literature and assessment of prognostic factors | journal = European Journal of Pain | volume = 10 | issue = 2 | pages = 91–101 | date = February 2006 | pmid = 16310712 | doi = 10.1016/j.ejpain.2005.02.004 | s2cid = 27988384 }} Although they improve patient pain and quality of life, evidence regarding their effects on mental health and general functioning is unclear.{{cite journal | vauthors = Visnjevac O, Costandi S, Patel BA, Azer G, Agarwal P, Bolash R, Mekhail NA | title = A Comprehensive Outcome-Specific Review of the Use of Spinal Cord Stimulation for Complex Regional Pain Syndrome | journal = Pain Practice | volume = 17 | issue = 4 | pages = 533–545 | date = April 2017 | pmid = 27739179 | doi = 10.1111/papr.12513 | s2cid = 20443171 }}

Dorsal root ganglion stimulation is a type of neurostimulation effective in managing focal neuropathic pain. The FDA approved its use in February 2016. The ACCURATE Study demonstrated superiority of dorsal root ganglion stimulation over spinal (dorsal column) stimulation in the management of CRPS and causalgia.{{cite journal | vauthors = Brucăr M | title = The cleavable hydatiform polycystic pseudotumoural disease | journal = Romanian Medical Review | year = 1969 | volume = 13 | issue = 3 | pages = 52–61 | pmid = 5359787 }}

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.{{cite journal | vauthors = Stanton-Hicks M, Baron R, Boas R, Gordh T, Harden N, Hendler N, Koltzenburg M, Raj P, Wilder R | display-authors = 6 | title = Complex Regional Pain Syndromes: guidelines for therapy | journal = The Clinical Journal of Pain | volume = 14 | issue = 2 | pages = 155–166 | date = June 1998 | pmid = 9647459 | doi = 10.1097/00002508-199806000-00012 }} However, little evidence supports these permanent interventions to alter the pain symptoms of the affected patients, and in addition to the normal risks of surgery, such as bleeding and infection, sympathectomy has several specific risks, such as adverse changes in how nerves function.{{citation needed|date=October 2020}}

No randomized study in the medical literature has studied the response to amputation of patients who have failed the therapies mentioned above and who continue to be in pain. Nonetheless, on average, about half of the patients will have resolution of their pain, while half will develop phantom limb pain and/or pain at the amputation site. As in any other chronic pain syndrome, the brain likely becomes chronically stimulated with pain, and late amputation may not work as well as it might be expected. In a survey of 15 patients with CRPS type 1, 11 responded that their lives were better after amputation.{{cite journal | vauthors = Bodde MI, Dijkstra PU, den Dunnen WF, Geertzen JH | title = Therapy-resistant complex regional pain syndrome type I: to amputate or not? | journal = The Journal of Bone and Joint Surgery. American Volume | volume = 93 | issue = 19 | pages = 1799–1805 | date = October 2011 | pmid = 22005865 | doi = 10.2106/JBJS.J.01329 | hdl = 11370/64f97da0-c435-4382-bd23-e0d91dad0c7e | s2cid = 12589466 | url = https://research.rug.nl/en/publications/64f97da0-c435-4382-bd23-e0d91dad0c7e }}

Cannabidiol, despite evidence of very low quality, is proposed to relieve pain.{{Cite web |title=WorkSafeBC |url=https://www.worksafebc.com/en/resources/health-care-providers/guides/ebpg-rapid-review-medical-or-synthetic-marijuana-as-treatment-for-complex-regional-pain-syndrome-crps?lang=en |access-date=2023-07-20 |website=www.worksafebc.com}}

The prognosis of CRPS is improved with early and aggressive treatment, with the risk of chronic, debilitating pain being reduced with the early treatment.{{cite journal | vauthors = Lloyd EC, Dempsey B, Romero L | title = Complex Regional Pain Syndrome | journal = American Family Physician | volume = 104 | issue = 1 | pages = 49–55 | date = July 2021 | pmid = 34264598 }} 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 worsens with the chronic "cold" form of CRPS and CRPS affecting the upper extremities. Inactivity of the limb following an injury, whether due to pain or recovery or, in some instances, psychological distress after the injury, can lead to deconditioning. The absence of movement contributes to muscle atrophy, swelling, joint stiffness and pain, and reduced circulation, among other processes. This sequence of physiological changes not only intensifies the symptoms of CRPS but is also associated with a less favorable prognosis. 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. Once one is diagnosed with CRPS, should it go into remission, the likelihood of it resurfacing after remission is considerable. Taking precautions and seeking immediate treatment upon any injury is important.{{cite web | title = Complex Regional Pain Syndrome (CRPS): Management and Treatment | publisher = Cleveland Clinic | url = https://my.clevelandclinic.org/health/diseases/12085-complex-regional-pain-syndrome-crps/management-and-treatment | access-date = 10 August 2020 | archive-date = 7 August 2020 | archive-url = https://web.archive.org/web/20200807092655/https://my.clevelandclinic.org/health/diseases/12085-complex-regional-pain-syndrome-crps/management-and-treatment | url-status = dead }}

CRPS can occur at any age, with the average age at diagnosis being 42.{{cite journal | vauthors = Veldman PH, Reynen HM, Arntz IE, Goris RJ | title = Signs and symptoms of reflex sympathetic dystrophy: prospective study of 829 patients | journal = Lancet | volume = 342 | issue = 8878 | pages = 1012–1016 | date = October 1993 | pmid = 8105263 | doi = 10.1016/0140-6736(93)92877-V | s2cid = 39843988 }} It affects both men and women; however, CRPS is three times more frequent in females than males.

CRPS affects both adults and children, and the number of reported CRPS cases among adolescents and young adults has been increasing,{{cite web |url=http://rsds.org/2/fact_fiction/index.html |title=RSDSA :: Reflex Sympathetic Dystrophy Syndrome Association |publisher=Rsds.org |date=2010-01-21 |access-date=2010-04-10 |url-status=dead |archive-url=https://web.archive.org/web/20100324094134/http://www.rsds.org/2/fact_fiction/index.html |archive-date=2010-03-24 }} with a recent observational study finding an incidence of 1.16/100,000 among children in Scotland.{{cite journal | vauthors = Abu-Arafeh H, Abu-Arafeh I | title = Complex regional pain syndrome in children: incidence and clinical characteristics | journal = Archives of Disease in Childhood | volume = 101 | issue = 8 | pages = 719–723 | date = August 2016 | pmid = 27005945 | doi = 10.1136/archdischild-2015-310233 | s2cid = 35072465 }}

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.{{cite journal | last=Iolascon | first=G | title=Complex regional pain syndrome (CRPS) type I: historical perspective and critical issues | journal=Clinical Cases in Mineral and Bone Metabolism | publisher=Edikta s.r.l. | year=2015 | issn=1971-3266 | doi=10.11138/ccmbm/2015.12.3s.004 | doi-access=free | page=| pmc=4832406 }} Silas Weir Mitchell is sometimes credited with inventing the name "causalgia" during the American Civil War.{{cite book | vauthors = Mitchell SE |author-link=Silas Weir Mitchell (physician) |title=Injuries of Nerves and their Consequences |url=https://archive.org/details/66230920R.nlm.nih.gov |publisher=JB Lippincott |location=Philadelphia |year=1872 }} 377 pages. However, the term was actually coined by Mitchell's friend Robley Dunglison from the Greek words for heat and pain.{{cite journal | vauthors = Richards RL | title = The term 'causalgia' | journal = Medical History | volume = 11 | issue = 1 | pages = 97–99 | date = January 1967 | pmid = 5341040 | pmc = 1033672 | doi = 10.1017/s0025727300011789 }} Causalgia, linked to neurological lesions, is significantly influenced by vasomotor and sudomotor symptoms. In the 1940s, the term "reflex sympathetic dystrophy" was introduced, highlighting the role of sympathetic hyperactivity in its pathophysiology.{{cite journal | vauthors = Evans JA | title = Reflex sympathetic dystrophy; report on 57 cases | journal = Annals of Internal Medicine | volume = 26 | issue = 3 | pages = 417–426 | date = March 1947 | pmid = 20288177 | doi = 10.7326/0003-4819-26-3-417 }} In 1959, Noordenbos observed in causalgia patients that "the damage of the nerve is always partial."{{cite book | vauthors = Noordenbos W |title=PAIN Problems pertaining to the transmission of nerve impulses which give rise to pain |publisher=Elsevier |location=Amsterdam |year=1959 |oclc=2008433|lccn=59008943}}{{page needed|date=June 2014}} 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 reflex sympathetic dystrophy as subtypes.{{cite journal | vauthors = Stanton-Hicks M, Jänig W, Hassenbusch S, Haddox JD, Boas R, Wilson P | title = Reflex sympathetic dystrophy: changing concepts and taxonomy | journal = Pain | volume = 63 | issue = 1 | pages = 127–133 | date = October 1995 | pmid = 8577483 | doi = 10.1016/0304-3959(95)00110-E | s2cid = 1085473 }}

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.{{Citation needed|date=December 2013}}

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.{{cite journal | vauthors = McCabe CS, Haigh RC, Ring EF, Halligan PW, Wall PD, Blake DR | title = A controlled pilot study of the utility of mirror visual feedback in the treatment of complex regional pain syndrome (type 1) | journal = Rheumatology | volume = 42 | issue = 1 | pages = 97–101 | date = January 2003 | pmid = 12509620 | doi = 10.1093/rheumatology/keg041 | publisher = Oxford University Press (OUP) | doi-access = free }} However, while CRPS can go into remission, the chance of it reoccurring is significant.{{citation needed|date=October 2020}}

The Netherlands has the most comprehensive program of research into CRPS, as part of a multimillion-Euro initiative called TREND.{{cite web | url = http://www.trendconsortium.nl/home-en | title =TREND homepage | archive-url = https://web.archive.org/web/20091224202308/http://www.trendconsortium.nl/home-en | archive-date=December 24, 2009 }}. German and Australian research teams are also pursuing better understanding and treatments for CRPS.{{citation needed|date=October 2020}}{{cite journal | vauthors = Raja SN, Grabow TS | title = Complex regional pain syndrome | journal = Anesthesiology | date = 2003 | volume = 98 | issue = 3 | pages = 1254–1260 | doi = 10.1097/00000542-200303000-00048 | doi-access = free |pmid=11981168}}

CRPS has also been described in non-human animals, such as cattle.{{cite journal | vauthors = Bergadano A, Moens Y, Schatzmann U | title = Continuous extradural analgesia in a cow with complex regional pain syndrome | journal = Veterinary Anaesthesia and Analgesia | volume = 33 | issue = 3 | pages = 189–192 | date = May 2006 | pmid = 16634945 | doi = 10.1111/j.1467-2995.2005.00245.x }}

• Paula Abdul, singer, actor, TV personalityPaula Abdul {{cite web|url=http://www.rarediseaseawareness.com/quality-of-life/paula-abdul-putting-the-spotlight-on-rare-disease |title=Paula Abdul: Putting the Spotlight on Rare Disease |access-date=2015-06-02 |url-status=dead |archive-url=https://web.archive.org/web/20150602094349/https://www.rarediseaseawareness.com/quality-of-life/paula-abdul-putting-the-spotlight-on-rare-disease |archive-date=2015-06-02 }}
• Jill Kinmont Boothe, US ski slalom champion{{cite news | vauthors = Crowe J | date = 22 May 2011 | newspaper = LA Times | title = Jill Kinmont Boothe is still going strong | url = https://www.latimes.com/sports/la-xpm-2011-may-22-la-sp-crowe-20110523-story.html }}
• Danielle Brown, British paralympic archer{{cite news | url=https://www.bbc.co.uk/sport/disability-sport/27064013 | title=Paralympic ban devastating - Brown | work=BBC Sport | date = 20 April 2014 }}
• Gemma Collis-McCann, British paralympic fencer{{cite web | title = Gemma Collis-McCann | url = https://paralympics.org.uk/athletes/gemma-collis-mccann | work = British Paralympic Association }}
• Radene Marie Cook, former Los Angeles radio broadcaster, artist, and advocate{{cite web | url=https://invisibleproject.org/radene-marie-cook/ | title=Radene Marie Cook | work = U.S. Pain Foundation | date=2017-12-02}}
• Shin Dong-wook, South Korean actor and model{{cite web | url=http://www.allkpop.com/2013/01/actor-shin-dong-wook-suffering-from-rare-disease | title=Actor Shin Dong Wook suffering from rare disease }}
• Howard Hughes, American business tycoon, aviator, inventor, filmmaker, and philanthropist{{cite journal| vauthors = Tennant F |date=July–August 2007 |title=Howard Hughes & Pseudoaddiction |url=http://pain-topics.org/pdf/HowardHughesPseudoaddict.pdf |journal=Practical Pain Management |volume=6 |issue=7 |pages=12–29 |access-date=January 7, 2011 |archive-url=https://web.archive.org/web/20070925191015/http://pain-topics.org/pdf/HowardHughesPseudoaddict.pdf |archive-date=September 25, 2007 |url-status=dead }}
• Maya Kowalski, subject of the 2023 documentary film Take Care of Maya{{cite web |last1=Etienne |first1=Vanessa |last2=Roedel |first2=Abby |title=A Shocking Accusation of Munchausen by Proxy Leads to a Mom's Death by Suicide: 'I Want Justice' (Exclusive) |url=https://people.com/take-care-of-maya-munchausen-by-proxy-accusation-maya-kowalski-mom-death-by-suicide-7509016 |website=People |access-date=28 September 2023 |date=7 June 2023}}
• Rachel Morris, British paralympic cyclist{{cite web | title = Rachel Morris | url = http://www.paralympics.org.uk/gb/athletes/rachel-morris | archive-url = https://web.archive.org/web/20120901232809/http://www.paralympics.org.uk/gb/athletes/rachel-morris | archive-date=2012-09-01 | work = British Paralympic Association }}
• Cynthia Toussaint, author and media personality{{cite web | vauthors = Burtt K | date = 13 March 2015 | veditors = Geehr EC | work = Lifescript | title = Cynthia Toussaint | url = http://www.lifescript.com/health/centers/pain/articles/how_a_hamstring_tear_derailed_a_dancers_life.aspx | archive-url = https://web.archive.org/web/20150627134742/http://www.lifescript.com/health/centers/pain/articles/how_a_hamstring_tear_derailed_a_dancers_life.aspx | archive-date=2015-06-27 }}
• Marieke Vervoort, Belgian Paralympic athlete{{Cite web|url=https://www.standaard.be/cnt/dmf20191022_04678477|title=Rolstoelatlete Marieke Vervoort is overleden|website=De Standaard | date = 22 October 2019 }}

{{Reflist}}

{{Medical resources

| DiseasesDB = 12635

| ICD10 = {{ICD10|M89.0}}

| ICD10CM = {{ICD10CM|G56.4}}

| ICD9 = {{ICD9|337.21}}, {{ICD9|337.22}}, {{ICD9|354.4}}, {{ICD9|355.71}}

| ICDO =

| OMIM =

| MedlinePlus = 007184

| eMedicineSubj = pmr

| eMedicineTopic = 123

| MeshID = D020918

| diseasesDB_mult = {{DiseasesDB2|16345}}

| Orphanet = 83452

| SNOMED CT = 128200000

}}

{{PNS diseases of the nervous system}}

{{Osteochondropathy}}

{{Authority control}}

{{DEFAULTSORT:Complex Regional Pain Syndrome}}

Category:Nerve, nerve root and plexus disorders

Category:Syndromes of unknown causes

Category:Chronic pain syndromes

Category:Neurocutaneous conditions

Category:Osteopathies

Category:Pain