Modern Principles of Diagnosis and Treatment in Complex Regional Pain Syndrome
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Background: Complex regional pain syndrome (CRPS) is a relatively common complication, occurring in 5% of cases after injury or surgery, particularly in the limbs. The incidence of CPRS is around 5–26/100 000. The latest revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-11) now categorizes CRPS as a primary pain condition of multifactorial origin, rather than a disease of the skeletal system or the autonomic nervous system.
Method: Based on a selective search of the literature, we summarize current principles for the diagnosis and treatment of CRPS.
Results: Regional findings in CRPS are accompanied by systemic symptoms, especially by neurocognitive disorders of body perception and of symptom processing. The therapeutic focus is shifting from predominantly passive peripheral measures to early active treatments acting both centrally and peripherally. The treatment is centered on physiotherapy and occupational therapy to improve sensory perception, strength, (fine) motor skills, and sensorimotor integration/ body perception. This is supported by stepped psychological interventions to reduce anxiety and avoidance behavior, medication to decrease inflammation and pain, passive physical measures for reduction of edema and of pain, and medical aids to improve functioning in daily life. Interventional procedures should be limited to exceptional cases and only be performed in specialized centers. Spinal cord and dorsal root ganglion stimulation, respectively, are the interventions with the best evidence.
Conclusion: The modern principles for the diagnosis and treatment of CRPS consider both, physiological and psychological mechanisms, with the primary goal of restoring function and participation. More research is needed to strengthen the evidence base in this field.
In 1994, after a number of previous different historical terms (e1, e2, e3, e4, e5, e6, e7, e8, e9, e10), complex regional pain syndrome (CRPS) was conceptualized for the first time by the “International Association for the Study of Pain” (IASP) (e10). Consensus criteria were established ten years later. They were revised in 2010 and slightly adapted in 2021 (Box 1) (1, 2).
The penultimate revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-9) had still classified essentially identical clinical conditions as “sympathetic reflex dystrophy” or “algoneurodystrophy”. On the one hand, ICD-10 mentions “neurodystrophy/algodystrophy” (which included sympathetic reflex dystrophy, Sudeck’s bone atrophy, shoulder-hand syndrome), while using the term “causalgia” if it developed after a nerve injury. In 2019, the term CRPS was included in the ICD-10. A distinction was made between Type 1 without nerve injury and Type 2 with nerve injury. Only shoulder-hand syndrome remained as “neurodystrophy/algodystrophy”.
On 1 December 2022, ICD-11 came into effect and is meanwhile also available as a German draft version (3, 4). It assigns both CRPS types and, for the first time, shoulder-hand syndrome together to a new symptom category—with a cross reference to chronic postoperative/post-traumatic pain (3, 4). “Chronic primary pain” now comprises, in addition to CRPS, other regional and widespread pain syndromes, such as chronic widespread pain/fibromyalgia syndrome, chronic primary low back pain, chronic primary visceral pain, and chronic primary headache. Common features, such as persistency, high emotional burden, and significant functional limitations are highlighted (2, 3, 4, e11). Chronic primary pain is referred to as “multifactorial” and sometimes as “nociplastic”, as opposed to nociceptive (thermic, mechanical) pain and neuropathic (nerve injury) pain (3, 4, e11, e12, e13, e14). “Nociplastic” is understood as a potentially reversible central hypersensitivity to stimuli without tissue or nerve damage (e12, e13, e14, e15, e16, e17, e18, e19, e20). Indeed, the mechanisms of developing CRPS are nowadays assumed primarily to be peripheral, spinal, and cerebral sensitization processes due to neurogenic inflammatory (auto-)immune response, autonomic dysregulation, and maladaptive protective behavior (learned disuse) (5, 6, 7, 8, 9, 10, 11, 12, 13, 14, e15, e21, e22, e23, e24, e25).
What are the implications of the new ICD-11 conceptual framework for clinical practical diagnostic and therapeutic strategies for CRPS?
The present review article takes a clinical interdisciplinary view of new diagnostic aspects and function-focuseded forms of treatment of CRPS. It follows the current German (15) and international CRPS guidelines and expert recommendations (16, 17, 18). A selective literature search was also conducted in PubMed for original articles and reviews published in English or German relating to the clinical presentation, course, (differential) diagnostics, and treatment of CRPS in adults. The search terms were “CPRS”, “complex regional pain syndrome”, “diagnosis”, “treatment”, “guideline”, “consensus”, and “recommendation”. The clinically most useful articles are cited directly, and a list of further reading is provided as e-references.
Incidence, inciting causes, risk factors
The incidence of CRPS is between 5 and 26 per 100 000 per year, its prevalence is about 20/100 000 (19, 20); numbers fluctuate strongly, depending on diagnostic criteria (8, 19, 20). Women are more commonly affected than men, with a ratio of 2–4 : 1 (19, 20, 21, e26, e27, e28). The age peak is around the 40th to 70th year of life (19, 20, 21, e26, e27, e28). However, CRPS occurs at any age, also affecting children and adolescents at a rate of about 1 to 5 per 100 000 (19, 20, 21, e26, e27, e29, e30).
In 0.2 to 9% of cases, CRPS develops after peripheral fractures or ligament injuries, in 2 to 5% after nerve injury, and in 1 to 13% after surgery of the extremities (8, e22, e23, e24, e25, e28, e31, e32, e33, e34, e35, e36, e37, e38, e39). On the other hand, 40 to 50% of all CRPS cases are preceded by fractures, and 30 to 40% are the result of other injuries or surgical procedures (1, 8, 19, 20, 21, e26, e27). Type and degree of tissue or nerve damage, immobilization, and high initial pain intensity increase the risk of developing CRPS (Box 2) (e28, e34, e35, e36, e37, e38, e39, e40, e41, e42). Yet even mild tissue injury can result in CRPS, for example, following arthroscopy, tourniquet application, snowball injury, injection, vaccination, or local infection (19, 20, e26, e27, e43, e44, e45). CRPS of the limbs (e.g., shoulder-hand syndrome) can also follow cerebral, spinal, and cardiac ischemia, degeneration, injuries, surgical procedures and, in isolated cases, malignant neoplasm, even though the tissue injury may lie far proximal to the site of manifestation (20, e27, e41, e46, e47, e48, e49, e50, e51, e52, e45, e46, e47, e48, e49, e50, e51). No initial event is clearly defined in about three to ten percent of cases (19, 20, 21, e27, e53). Painful pre-existing conditions (e54, e55, e56, e57) and stressful life events (6, 22, e58, e59), even without tissue injury (6), can precede CRPS (Box 2).
There is conflicting data on psychological risk factors for developing CRPS. Overall, the rate of premorbid and comorbid post-traumatic stress disorders (PTSD) appears to be increased: 27 to 38% fulfill all, 56% most criteria (22, e59). Anxiousness and pain catastrophizing appear to both increase the risk of disease (e60) and worsen its prognosis (e61, e62, e63). Most studies, however, do not show an increased rate of depression, anxiety disorders, or personality disorders as compared with other diseases (22, e33, e37, e42, e57, e58, e59, e60, e61, e62, e63, e64, e65, e66) (Box 2).
Clinical presentations and diagnostic criteria
The cardinal symptoms of CRPS are regional pain and other sensory, motor, autonomic, and trophic disturbances (Box 1). Distal extremities are by far the most common sites of manifestation of CRPS, with the hands being affected more often than the feet. The symptoms have a “glove-” or “sock-like” distribution and do not correspond to a dermatome or area of innervation. There have been isolated reports of CRPS affecting, amongst other sites, the face and trunk (e45, e67, e68, e69).
To establish a CRPS diagnosis, the Budapest criteria must be met—as per the current guidelines, too (Box 1) (1, 2, 3, 4, 15, 16, 17, 18). Their sensitivity is around 98 to 99%, their specificity about 36 to 68% (1, 8, e46, e57). The entry criterion is continuing pain disproportionate to any inciting event (in 1994 it was still “harmful event or immobilization” [e10]). Neither the disproportionality nor the potential inciting cause is defined more precisely. No other disorder, including the primary injury, better explains the signs and symptoms (1, 15, 16, 17, 18). There is no time criteria; the CRPS guideline of the German Neurological Society (DGN) specifies two to three months as a reasonable time point (15) by which all criteria must be fulfilled, bearing in mind that the healing process of the primary injury still needs to be awaited.
The majority of patients present other symptoms, in particular top-down disturbances of body perception and symptom processing (7, 8, 9, 10, 11, 12, 15, 16, 17, 22, 23, e70, e71, e72, e73, e74, e75, e76, e77, e78, e79, e80, e81, e82, e83, e84, e85, e86, e87, e88, e89, e90, e91, e92, e93, e94, e95, e96, e97, e98, e99, e100, e101, e102, e103, e104, e105, e106, e107, e108) (Box 3). For example, between 32 and 84% have neuropsychological symptoms relating to the affected limb, i.e., disturbances of alertness/attentiveness, sense of body ownership/sense of position, experience of authorship/control of actions, and attribution of meaning/emotions (7, 23, e69, e70, e71, e72, e73, e74, e75, e76, e77, e78, e79, e80, e81), even in the form of depersonalization (e82) or alexithymia, i.e., a reduced ability to identify emotions experienced by themselves and others (e83). A combination of finger misperception and body image disturbance differentiated between patients with CRPS and those with fractures with a specificity of 85% and a positive predictive value of 84% (e84).
There appear to be clinical, possibly pathophysiological, overlaps with neuropathic pain syndromes (15, 16, 17, 18, e101, e102, e103), as well as with other chronic primary pain syndromes (3, 4, 18, e11, e12, e13, e14, e104, e105, e106, e107, e108) and functional (e18), (especially functional neurological) disorders, defined as involuntary discontinuity of the normal integration of motor, sensory, cognitive functions (7, 9, 11, 12, e109, e110, e111, e112, e113, e114), and PTSD (6, 22, e59, e80). Modern guidelines recommend assessing affective disturbances and body perception disturbances, especially post-traumatic stress symptoms, attentional disturbances, fear of touch or of movement (15, 16, 17, 18). So far, however, such features have not been included in any diagnostic criteria (1, 2, 3, 4) (Box 3).
Technical and laboratory findings are not included in the diagnostic criteria either (1, 2, 3, 4): CRPS is and remains a clinical diagnosis. If history and clinical examination have established the diagnosis, then no guideline recommends any further diagnostic investigations (15, 16, 17, 18). To help substantiate the diagnosis, the DGN CRPS guideline recommends a three-phase bone scan only during the first year of disease in cases of doubt or if an expert opinion is required in the foreseeable future (15). Additional diagnostic investigations, however, allow sound differential diagnostics in accordance with the 4th Budapest criterion (eBox) (15, 16, 18, e115, e116, e117, e118, e119, e120, e121, e122, e123, e124, e125, e126).
Subtypes, clinical course, prognosis
Differentiation between CRPS 1 and 2 is controversial, given that, clinically, there is no difference (2, 8, 15, 16, 17, 18, e28). Modern guidelines do not express any difference in recommendations between the two (15, 16, 17, 18). The distinction between “warm” and “cold” CRPS subtypes or stages, however, is of some clinically relevance with regard to treatment (see below) (8, 15, 17, e127, e128, e129). The “warm” subtype is often described as “red”, “sweaty”, and “early”. The “cold” subtype is characterized as “blue”, “dystrophic/atrophic”, “late” and regarded as having a less favorable prognosis. Depending on the situation, vasomotor and sudomotor symptoms, such as skin color changes and sweating, may fluctuate (2, 3, 4, 10, 13) as an indication of central neurogenic regulation – there is possibly a peripheral inflammatory etiology behind “warm” CRPS signs and symptoms, while “cold” CRPS is of a central nervous nociplastic origin (13, e21). The DGN CRPS guideline refers to acute (less than 6 months) as opposed to chronic CRPS (15), while current US-American and British recommendations distinguish between early (less than 18 months) and persistent CRPS (18). New CRPS subtypes (“CRPS with remission of some features” and “not otherwise specified”) were proposed for subsyndromal courses which no longer fully meet the diagnostic criteria or never have (2).
CRPS usually settles within three to 13 months, sometimes even without treatment (20, 21, 24, e28, e74, e130, e131). Complete remissions are rare, though, and difficult to define (21, 24, e132). In more than one half of adult patients at least some of the signs and symptoms persist, especially pain and motor symptoms (20, 24, e28, e74, e130). Although most patients return to work, one third require workplace adaptations, and one third remain permanently unfit for work (20, 24, e74, e130). In about 7%, the CRPS spreads to involve other limbs without any further traumatic event (2, 16, 17, e74, e133, e134).
Differential diagnostic challenges
The differential diagnosis of CRPS is wide-ranging, which inevitably carries with it the risk of being missed or even becoming subject to diagnostic inflation or a diagnosis of convenience (Table 1) (15, 16, 17, 20, 25, e135). Findings are sometimes difficult to objectify, resulting in discrepancies between history and examination as well as between one examination situation to another (2, 15, 16, 17, 18, 25, e136). The fact that the CRPS diagnostic criteria demand that the pain should be disproportionate to the inciting event can lead to it being wrongly attributed to trivial trauma (11). Focus is therefore on a detailed history, clinical examination, and differential diagnostic considerations from an interdisciplinary perspective, together with a careful assessment of the primary injury and repeated (photographic) documentation (2, 15, 16, 17, 18, 25). The Budapest criteria are assessed in comparison with the healthy side, paying due respect to risk factors and additional symptoms (Box 1, Box 3).
A particular distinction must be made from rheumatic, vascular/vasomotor, infectious, (functional) neurological, psychosomatic/psychiatric disorders, and complications from previous treatment (Table 1) (11, 15, 16, 17, 20, 25, e23, e24, e25, e110, e111, e112, e113, e114, e135, e136, e137, e138, e139, e140, e141, e142). The longer CRPS has been present, the more difficult is the differentiation from chronic non-use/underuse of other origin (15). Referral to an interdisciplinary center should be arranged if there are any doubts, complications (symptom spread, fixed dystonia, skin lesions/infections, malignant edema, severe psychological burden, desire for amputation), or no improvement after about two months (15, 16, 17, 18) (Table 1).
Examinations in the medicolegal setting reveal high rates of simulation, somatoform/functional disorders, opioid dependency (e143, e144, e145), as well as deterioration of signs and symptoms instead of improvement over time (e136). For the purposes of an expert opinion with near complete proof of causality, the diagnosis of CRPS is often insufficient: The German pain assessment guideline refers to CRPS as an “extraordinary chronic pain syndrome” and a “special case”, and rejects trivial trauma as a negligible and interchangeable cause (e135, e146). For confirmation of a comprehensible causal relationship, it demands a (contentiously early) onset of symptoms within a few days to two weeks after the inciting event.
Treatment is centered around an inflammatory and particularly sensitive acute phase and an early and late rehabilitation (Table 2) (15, 16, 17, 18, e147). Prior to that, it is worth considering prevention even before CRPS becomes manifest. The key therapeutic principle is functional restoration, guided by graded occupational therapy and physiotherapy—Harden et al. (18) even spoke of “reanimation”. This is facilitated by psychological, physical, pharmacological, and, in individual cases, invasive pain management (15, 16, 17, 18). The primary therapeutic goal is a lasting improvement of function and participation. With this in mind, chances and risks of all therapeutic measures must be weighed up against each other. Possible barriers to recovery, including iatrogenic issues, must be taken into account (15, 16, 17, 18). Throughout every phase of treatment, all passive, fear or pain amplifying, and movement restricting measures against the patient’s will or outside the patient’s control, including unannounced touching and nocebo messages, are contraindicated (15, 16, 17, 18).
Of central importance are as little tissue traumatization and immobilization as possible, adequate pain relief, and detailed information for the patient with regard to normal findings and ranges of movement (Table 2) (8, 15, 16, 17, 18, e23, e24, e25, e125, e148, e149, e150, e151, e152, e153, e154). The incidence of CRPS after radius fractures appears to fall if patients are taught light range-of-motion exercises early on (e153); physiotherapy and occupational therapy, together with explicit motor imagery (see below), appear to reduce pain and improve function (e154). There is some controversy concerning any preventive anti-inflammatory effect of ascorbic acid (16, 17, 18, e155, e156); this agent does not find mention in the DGN CRPS guideline (15).
The treatment of manifest CRPS
Treatments are usually delivered within individually tailored, multimodal programs that have been shown to be effective (15, 16, 17, 18, 26, 27, 28, e23, e24, e25, e146, e157, e158, e159, e160, e161, e162). Available data supporting specific individual interventions (see below) are insufficient, comprising only a few randomized controlled trials, mostly involving small or (considering the low specifity of diagnostic criteria) heterogeneous populations (Table 2).
Active forms of treatment
Physiotherapy and occupational therapy
The key recommendation of current guidelines throughout all treatment phases is physiotherapy and occupational therapy, together with neurocognitive elements or components of behavioral therapy aiming at the normalization of sensorimotor integration. This is achieved by graded exposure to strength and movement as well as visuo-tactile stimulation and discrimination (Table 2) (8, 15, 16, 17, 18, 29, 30, 31, e23, e24, e25, e163, e164, e165, e166, e167, e168, e169, e170, e171, e172, e173, e174, e175, e176, e177, e178, e179, e180, e181, e182, e183, e184, e185):
- The Perfetti method and graded motor imagery are directed towards cortical reorganization by means of left-right discrimination training (recognizing photos of limbs in different positions of function), explicit motor imagery, and mirror therapy (projecting the healthy, positively connotated limb onto the affected side) (8, 15, 16, 17, 18, 29, 30, 31, e23, e24, e25, e80, e163, e164, e165, e166, e167, e168, e169, e170, e171, e172). The patient is introduced as early as possible to individual leisure activities/work requirements by self-exercises, also with the help of computer applications (e173, e174, e175, e176, e177, e178, e179, e180, e181). Mirror therapy appears to be particularly effective for post-stroke CRPS (15, 29 e168), but it is not sufficient on its own for the majority of cases. Indeed, mirror therapy can even make individual cases worse, or result in the development of symptoms on the contralateral side, (15, 29, e169). Overall, neurocognitive procedures appear to improve function more than alleviate pain (27, 29, e169).
- There is adequate proof that graded exposure can improve function, pain, and fear (15, 16, 17, 18, 26, e182). Perceptual disturbances, kinesiophobia and dysfunctional protective behavior are adressed and gradually reduced by graded exposure and the violation of dysfunctional expectations. In such an approach, occupational therapy, physiotherapy and psychology work closely together.
Pain exposure without psychological support is a subject of controversy because of frequent discontinuations of treatment; therefore, it is no longer recommended (15, 18, 26, 31). Self-efficacy, fitness and body-mind techniques, integrated into an overall treatment concept which includes playful or meditative methods, often in groups, can additionally improve body perception and control in a cost-effective way with few side effects (Table 2, 16, 17, 26, e24). Studies dealing with this, however, are lacking.
Current guidelines recommend stepped psychological interventions (Table 2) (15, 16, 17, 18):
- Teaching a biopsychosocial explanatory model which provides motivation and instructions for the best possible active and fear-free use of the limb (psychoeducation) is conducted immediately by the attending “somatic” healthcare staff (15, 16, 17, 18, e152, e153). For this purpose, patients need information, repeated often and in reassuring, layman’s language, which they can then put into action.
- Within the framework of multimodal treatment, clinical psychologists conduct a more differentiated form of psychological pain therapy, oriented predominantly towards cognitive behavioral therapy and often also in groups to enable exchange with fellow patients (15, 16, 17, 18).
- Guideline-based psychotherapy provided by board-certified medical/psychological psychotherapists may be indicated for intractable cases and patients with considerable biographical or current stresses and strains and/or mental comorbidity (15, 16, 17, 18).
However, the level of evidence covering psychoeducative/psychological and, above all, psychotherapeutic interventions for CRPS is low and for the most part derived from other chronic pain disorders (8, 15, 16, 17, 18, 34, e23, e24, e25, e159, e186, e187, e188, e189, e190, e191, e192).
Passive forms of treatment
The focus of pharmacotherapy (eTable 1) is also primarily on maintaining function (15, 16, 17, 18): Sedatives, for example, improve tension and sleep disturbances, yet interfere with treatment cooperation and participation (fitness to drive!). It is important to inform patients in detail about risks/side effects, the need to gradually increase the dose until adequate levels are reached, to consider a possible delayed, sometimes absent, effect, and to discontinue or withdraw if necessary (15, 16, 17, 18, 34, e193). Medication needs decrease and self-efficacy improves by incorporating active, non-pharmacological interventions such as relaxation methods.
Pharmacotherapy is based almost without exception on off-label drugs where evidence is limited (eTable 1) (8, 15, 16, 17, 18, 26, 27, 28, 32, e23, e24, e25, e194, e195, e196, e197, e198, e199, e200, e201, e202, e203, e204, e205, e206, e207, e208, e209). Current treatment recommendations vary: The German guideline recommends anti-inflammatory bis-phosphonates and steroids which are of equal value for the acute inflammatory phase (15), the British guideline recommends only bisphosphonates (16), while the position paper of the European Pain Federation recommends neither (17). The DGN CRPS guideline regards oral pain pharmacotherapy as a basic measure (15) and recommends gabapentinoids with some reservations and ketamine with strict indications (15). Other guidelines are more cautious and recommend prescribing analgesics only when stopping rules are established due to their frequent ineffectiveness and side effects (17) or only when functional restoration is not possible without them (18). Beyond that, many guidelines refer to the more established treatment recommendations that exist for neuropathic pain (for example, the use of gabapentinoids, antidepressants, possibly botulinum toxin, 15, 16, 17, 33, e209), although even CRPS 2 only partially meets the definition of neuropathic pain (18, e210).
Current guidelines hardly mention the use of topical agents with their various chemical properties (15, 16, 17, 18). Their advantage lies in their minimal side effects. In addition, the tactile stimulus when applied by the patients themselves provides better somatotopic representation and motor control. The German guideline points out that dimethyl sulfoxide cream is standard therapy in the Netherlands (15, 26). Other substances with an effect on the central nervous system, such as naltrexone and memantine, as well as immunomodulatory drugs are regarded as experimental and thus not yet recommended (15, 16, 17, 18, 26, 27, 28, 32, e24, e160, e211, e212).
Physical therapy and medical aids
Passive physical measures, including transcutaneous electrical nerve stimulation (TENS) and acupuncture, are directed primarily at edema and pain relief, and medical aids towards better functionality (Table 2). According to modern guidelines, manual lymphatic drainage is suitable for edema treatment (15, 17), while other procedures are either not mentioned at all or only briefly touched (16, 17, 18, 26). There are hardly any studies on this, and these are contradictory. (15, 16, 17, 18, 26, 27, 28, e24, e213, e214, e215, e216, e217).
Where interventional measures reduce—albeit temporarily—pain and restricted movement, they open a window of opportunity for active rehabilitation. Given that they are associated with higher costs, risks and, possibly, repeated experience of pain and helplessness, however, they require a strict indication, especially when they are demanded by the patients themselves (15, 16, 17, 18). They are reserved for unequivocal, severe CRPS where conservative measures have been exhausted (15, 16, 17, 18).
According to current guidelines, including the DGN CRPS guideline, there is the option of spinal cord stimulation for intractable CRPS of the lower limbs (eTable 2) (15, 16, 17, 18, 26, e218). Recent reviews and a current randomized comparative study suggest that direct dorsal nerve root stimulation has probably fewer side effects and is longer lasting than spinal cord stimulation (15, 18, 34, e219, e220, e221, e222, e223, e224). Intrathecal baclofen may be considered for intractable dystonia (15, 16, 18). So far the evidence is not convincing for any other approaches; for example, with regard to the duration of action of transcranial magnetic stimulation, and the risk-benefit profile of more invasive methods (eTable 2) (15, 16, 17, 18, 26, 27, 28, e23, e24, e25, 34, e225, e226, e227, e228, e229, e230, e231, e232, e233, e234, e235, e236, e237).
Peripheral and central, physiological and psychological mechanisms appear to work together in CRPS. Diagnosis specificity and treatment effectiveness seem to improve when neuropsychobehavioral findings are taken into consideration. This is reflected in modern guidelines and the IDC-11, but not yet in the CRPS diagnostic criteria. Sensitive early warning signals, specific clinical criteria and biomarkers, as well as properly targeted prevention/treatment strategies should be further developed—while still maintaining a differentiated look at comorbidities und differential diagnosis.
Conflict of interest statement
Dr. Böhringer received fees from Grünenthal for a presentation.
Prof. Hausteiner-Wiehle received lecture fees and reimbursement of travel expenses from Windach Hospital and the Lindau Psychotherapy Weeks.
Alexandra Melf-Marzi and Dr. Wiehle declare that no conflict of interest exists.
Manuscript received on 21 April 2022, revised version accepted on 17 October 2022.
Translated from the original German by Dr. Grahame Larkin MD
Prof. Dr. med. Constanze Hausteiner-Wiehle
Department for Neurology, Clinical Neurophysiology and Stroke Unit
BG Trauma Center Murnau, Prof.-Küntscher-Strasse 8, 82418 Murnau
Cite this as:
Melf-Marzi A, Böhringer B, Wiehle M, Hausteiner-Wiehle C:
Modern principles of diagnosis and treatment in complex regional pain syndrome.
Dtsch Arztebl Int 2022; 119: 879–86. DOI: 10.3238/arztebl.m2022.0358
eReferences, eTables, eBox:
This article has been certified by the North Rhine Academy for Continuing Medical Education. Participation in the CME certification program is possible only over the internet: cme.aerzteblatt.de. The deadline for submission is 26 December 2023.
Department for Anesthesiology, Intensive Care Medicine and Pain Therapy; Multimodal Pain Therapy; BG Trauma Center Murnau: Dr. med. Bettina Böhringer
Department for Neurology, Clinical Neurophysiology and Stroke Unit; BG Trauma Center Murnau: Dr. med. Matthias Wiehle, Prof. Dr. med. Constanze Hausteiner-Wiehle
Clinic and Polyclinic for Psychosomatic Medicine and Psychotherapy, Klinikum rechts der Isar, Technical University of Munich: Prof. Dr. med. Constanze Hausteiner-Wiehle
|1.||Harden RN, Bruehl S, Perez RS, et al.: Validation of proposed diagnostic criteria (the “Budapest Criteria”) for complex regional pain syndrome. Pain 2010; 150: 268–74 CrossRef MEDLINE PubMed Central|
|2.||Goebel A, Birklein F, Brunner F, et al.: The valencia consensus-based adaptation of the IASP complex regional pain syndrome diagnostic criteria. Pain 2021; 162: 2346–8 CrossRef MEDLINE PubMed Central|
|3.||World Health Organization: International Classification of Disease 11th Revision. www.icd.who.int/browse11/l-m/en (last accessed on 17 August 2022).|
|4.||Bundesinstitut für Arzneimittel und Medizinprodukte: ICD-11 in Deutsch – Entwurfsfassung. www.bfarm.de/DE/Kodiersysteme/Klassifikationen/ICD/ICD-11/uebersetzung/_node.html (last accessed on 17 August 2022).|
|5.||Maihöfner C, Handwerker HO, Neundörfer B, Birklein F: Cortical reorganization during recovery from complex regional pain syndrome. Neurology 2004; 63: 693–701 CrossRef MEDLINE|
|6.||Grande LA, Loeser JD, Ozuna J, Ashleigh A, Samii A: Complex regional pain syndrome as a stress response. Pain 2004; 110: 495–8 CrossRef MEDLINE|
|7.||Punt DT, Cooper L, Hey M, Johnson MI: Neglect-like symptoms in complex regional pain syndrome: learned nonuse by another name? Pain 2013; 154: 200–3 CrossRef MEDLINE|
|8.||Bruehl S: Complex regional pain syndrome. BMJ 2015; 351: h2730 CrossRef MEDLINE|
|9.||Hausteiner-Wiehle C, Henningsen P: Do we have to rethink complex regional pain syndrome? J Psychosom Res 2018; 111: 13–4 CrossRef MEDLINE|
|10.||Knudsen LF, Terkelsen AJ, Drummond PD, Birklein F: Complex regional pain syndrome: a focus on the autonomic nervous system. Clin Auton Res 2019; 29: 457–67 CrossRef MEDLINE|
|11.||Popkirov S, Hoeritzauer I, Colvin L, Carson AJ, Stone J: Complex regional pain syndrome and functional neurological disorders—time for reconciliation. J Neurol Neurosurg Psychiatry 2019; 90: 608–14 CrossRef MEDLINE|
|12.||Halicka M, Vittersø AD, Proulx MJ, Bultitude JH: Neuropsychological changes in Complex Regional Pain Syndrome (CRPS). Behav Neurol 2020; 2020: 4561831 CrossRef MEDLINE PubMed Central|
|13.||Dimova V, Herrnberger MS, Escolano-Lozano F, et al.: Clinical phenotypes and classification algorithm for complex regional pain syndrome. Neurology 2020; 94: e357–67 CrossRef MEDLINE|
|14.||Goebel A, Andersson D, Helyes Z, Clark JD, Dulake D, Svensson C: The autoimmune aetiology of unexplained chronic pain. Autoimmun Rev 2022; 21: 103015 CrossRef MEDLINE|
|15.||S1-Leitlinie: Diagnostik und Therapie komplexer regionaler Schmerzsyndrome (CRPS), 2018. www.awmf.org/leitlinien/detail/ll/030-116.html (last accessed on 15 August 2022).|
|16.||Goebel A, Barker CH, Turner-Stokes L, et al.: Complex regional pain syndrome in adults: UK guidelines for diagnosis, referral and management in primary and secondary care. London: RCP, 2018. www.rcplondon.ac.uk/guidelines-policy/complex-regional-pain-syndrome-adults (last accessed on 15 August 2022).|
|17.||Goebel A, Barker C, Birklein F, et al.: Standards for the diagnosis and management of complex regional pain syndrome: results of a European Pain Federation task force. Eur J Pain 2019; 23: 641–51 CrossRef MEDLINE PubMed Central|
|18.||Harden RN, McCabe CS, Goebel A, et al.: Complex regional pain syndrome: practical diagnostic and treatment guidelines, 5th edition. Pain Med 2022; 23: 1–53 CrossRef MEDLINE PubMed Central|
|19.||de Mos M, de Bruijn AG, Huygen FJ, Dieleman JP, Stricker BH, Sturkenboom MC: The incidence of complex regional pain syndrome: a population-based study. Pain 2007; 129: 12–20 CrossRef MEDLINE|
|20.||Sandroni P, Benrud-Larson LM, McClelland RL, Low PA: Complex regional pain syndrome type I: incidence and prevalence in olmsted county, a population-based study. Pain 2003; 103: 199–207 CrossRef MEDLINE|
|21.||de Mos M, Huygen FJ, van der Hoeven-Borgman M, Dieleman JP, Stricker BHC, Sturkenboom MC: Outcome of the complex regional pain syndrome. Clin J Pain 2009; 25: 590–7 CrossRef MEDLINE|
|22.||Speck V, Schlereth T, Birklein F, Maihöfner C: Increased prevalence of posttraumatic stress disorder in CRPS. Eur J Pain 2017; 21: 466–73 CrossRef MEDLINE|
|23.||Tschopp M, Swanenburg J, Wertli MW, et al.: Die deutsche Version der Bath Body Perception Disturbance Scale (BBPDS-D). Schmerz 2018; 32: 195–200 CrossRef MEDLINE|
|24.||Johnson S, Cowell F, Gillespie S, Goebel A: Complex regional pain syndrome what is the outcome?—a systematic review of the course and impact of CRPS at 12 months from symptom onset and beyond. Eur J Pain 2022; 26: 1203–20 CrossRef MEDLINE PubMed Central|
|25.||Terkelsen AJ, Birklein F: Complex regional pain syndrome or limb pain: a plea for a critical approach. J Pain Res 2022; 15: 1915–23 CrossRef MEDLINE PubMed Central|
|26.||Perez RS, Zollinger PE, Dijkstra PU, et al.: CRPS I task force: Evidence based guidelines for complex regional pain syndrome type 1. BMC Neurol 2010; 10: 20. Update: www.crps-vereniging.nl/pdf/Executive_summary_guideline_CRPS_I_2014_ docx.pdf (last accessed on 22 February 2022) CrossRef MEDLINE PubMed Central|
|27.||O‘Connell NE, Wand BM, McAuley J, Marston L, Moseley GL: Interventions for treating pain and disability in adults with complex regional pain syndrome. Cochrane Database Syst Rev 2013; 2013: CD009416 CrossRef PubMed Central|
|28.||Duong S, Bravo D, Todd KJ, Finlayson RJ, Tran Q: Treatment of complex regional pain syndrome: an updated systematic review and narrative synthesis. Can J Anaesth 2018; 65: 658–84 CrossRef MEDLINE|
|29.||Thieme H, Morkisch N, Rietz C, et al.: The efficacy of movement representation techniques for treatment of limb pain—a systematic review and meta-analysis. J Pain 2016; 17: 167–80 CrossRef MEDLINE|
|30.||Lotze M, Moseley GL: Clinical and neurophysiological effects of progressive movement imagery training for pathological pain. J Pain 2022; 23: 1480–91 CrossRef MEDLINE|
|31.||Smart KM, Ferraro MC, Wand BM, O‘Connell NE: Physiotherapy for pain and disability in adults with complex regional pain syndrome (CRPS) types I and II. Cochrane Database Syst Rev 2022; 5: CD010853 CrossRef MEDLINE|
|32.||Fassio A, Mantovani A, Gatti D, et al.: Rheumatology (Oxford). Pharmacological treatment in adult patients with CRPS-I: a systematic review and meta-analysis of randomised controlled trials. Rheumatology (Oxford) 2022; 61: 3534–46 CrossRef MEDLINE|
|33.||S2k-Leitlinie: Diagnose und nicht interventionelle Therapie neuropathischer Schmerzen. www.awmf.org/leitlinien/detail/ll/030–114.html (last accessed on 11 August 2022).|
|34.||Chmiela MA, Hendrickson M, Hale J, et al.: Direct peripheral nerve stimulation for the treatment of complex regional pain syndrome: a 30-year review. Neuromodulation 2021; 24: 971–82 CrossRef MEDLINE|
|e1.||Mitchell SW, Morehouse GR, Keen WW: Gunshot wounds and other injuries of nerves. 1864. Clin Orthop Relat Res 2007; 35–9 CrossRef|
|e2.||Charcot JM: Clinique des maladies du systeme nerveux. Paris: Presse Medicale 1892.|
|e3.||Sudeck P: Über die akute entzündliche Knochenatrophie. Arch Klin Chir 1900; 62: 147–56.|
|e4.||Oppenheimer H: Die traumatischen Neurosen nach den in der Nervenklinik der Charite in den letzten 5 Jahren gesammelten Beobachtungen. Berlin: Verlag von August Hirschwald 1889.|
|e5.||Cassirer R: Die vasomotorisch-trophischen Neurosen. Berlin: S. Karger 1901.|
|e6.||Cramer K: Über metatraumatische vasomotorisch-trophische Neurosen. Archiv für Orthopädie, Mechanotherapie und Unfallchirurgie 1909; 7: 341–60 CrossRef|
|e7.||Leriche R: De la causalgie envisagee comme une nevrite due sympathique et de son traitment par la denudation et l’excision des plexus nerveux peri-arteriels. Paris: Presse Medicale 1916.|
|e8.||Babinski J, Froment J: Hystérie-pithiatisme et troubles nerveux d‘ordre réflexe en neurologie de guerre. Paris: Masson et Cie 1917.|
|e9.||Evans JA: Reflex sympathetic dystrophy. Surg Clin North Am 1946; 26: 780–90.|
|e10.||Merskey H, Bogduk N: International Association for the Study of Pain. Task Force on Taxonomy: classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms. 2nd edition. Seattle (WA): IASP Press 1994.|
|e11.||Nicholas M, Vlaeyen JWS, Rief W, et al.: IASP Taskforce for the Classification of Chronic Pain. The IASP classification of chronic pain for ICD-11: chronic primary pain. Pain 2019; 160: 28–37.|
|e12.||Treede RD, Hoheisel U, Wang D, Magerl W: Central sensitization: clinical utility of a physiological concept for the International Statistical Classification of Diseases and Related Health Problems and for nociplastic pain. Pain 2022; 163 (Suppl 1): 99–107.|
|e13.||Popkirov S, Enax-Krumova EK, Mainka T, Hoheisel M, Hausteiner-Wiehle C: Functional pain disorders—more than nociplastic pain. NeuroRehabilitation 2020; 47: 343–53.|
|e14.||Fitzcharles MA, Cohen SP, Clauw DJ, Littlejohn G, Usui C, Häuser W: Nociplastic pain: towards an understanding of prevalent pain conditions. Lancet 2021; 397(10289): 2098–110.|
|e15.||Moseley GL: Reconceptualising pain according to its underlying biology. Phys Ther Rev 2007; 12: 169–78.|
|e16.||Wiech K: Deconstructing the sensation of pain: the influence of cognitive processes on pain perception. Science 2016; 354 (6312): 584–7.|
|e17.||Di Lernia D, Serino S, Riva G: Pain in the body. Altered interoception in chronic pain conditions: a systematic review. Neurosci Biobehav Rev 2016; 71: 328–41.|
|e18.||Henningsen P, Gündel H, Kop WJ, et al.: EURONET-SOMA Group: persistent physical symptoms as perceptual dysregulation: a neuropsychobehavioral model and its clinical implications. Psychosom Med 2018; 80: 422–31.|
|e19.||Greenwald JD, Shafritz KM: An integrative neuroscience framework for the treatment of chronic pain: from cellular alterations to behavior. Front Integr Neurosci 2018; 12: 18.|
|e20.||Kuner R, Kuner T: Cellular circuits in the brain and their modulation in acute and chronic pain. Physiol Rev 2021; 101: 213–58.|
|e21.||Birklein F, Schlereth T: Complex regional pain syndrome—significant progress in understanding. Pain 2015; 156: 94–103.|
|e22.||Birklein F, Ajit SK, Goebel A, Perez RSGM, Sommer C: Complex regional pain syndrome—phenotypic characteristics and potential biomarkers. Nat Rev Neurol 2018; 14: 272–84.|
|e23.||Shim H, Rose J, Halle S, Shekane P: Complex regional pain syndrome: a narrative review for the practising clinician. Br J Anaesth 2019; 123: e424–e33.|
|e24.||Taylor SS, Noor N, Urits I, et al.: Complex regional pain syndrome: a comprehensive review. Pain Ther 2021; 10: 875–92.|
|e25.||Rebhorn C, Dimova V, Birklein F: Komplexes regionales Schmerzsyndrom—ein Update. Nervenarzt 2021; 92: 1075–83.|
|e26.||Ott S, Maihöfner C: Signs and symptoms in 1,043 patients with complex regional pain syndrome. J Pain 2018; 19: 599–611.|
|e27.||Birklein F, Riedl B, Sieweke N, Weber M, Neundörfer B: Neurological findings in complex regional pain syndromes—analysis of 145 cases. Acta Neurol Scand 2000; 101: 262–9.|
|e28.||Beerthuizen A, Stronks DL, Van‘t Spijker A, et al.: Demographic and medical parameters in the development of complex regional pain syndrome type 1 (CRPS1): prospective study on 596 patients with a fracture. Pain 2012; 153: 1187–92.|
|e29.||Baerg K, Tupper SM, Chu LM, et al.: Canadian surveillance study of complex regional pain syndrome in children. Pain 2022; 163: 1060–9.|
|e30.||Abu-Arafeh H, Abu-Arafeh I: Complex regional pain syndrome in children: incidence and clinical characteristics. Arch Dis Child 2016; 101: 719–23.|
|e31.||Duenes M, Schoof L, Schwarzkopf R, Meftah M: Complex regional pain syndrome following total knee arthroplasty. Orthopedics 2020; 43: e486–e491.|
|e32.||Magone KM, Ben-Ari E, Hacquebord JH, Virk MS: Complex region pain syndrome following shoulder surgery. Arthrosc Sports Med Rehabil 2021; 3: e1037–45.|
|e33.||Bruehl S, Billings FT 4th, Anderson S, et al.: Preoperative predictors of complex regional pain syndrome outcomes in the 6 months following total knee arthroplasty. J Pain 2022: 23: 1712–23.|
|e34.||Sousa LHA, O Costa C, Novak EM, Giostri GS: Complex regional pain syndrome after carpal tunnel syndrome surgery: a systematic review. Neurol India 2022; 70: 491–503.|
|e35.||Roh YH, Lee BK, Noh JH, et al.: Factors associated with complex regional pain syndrome type I in patients with surgically treated distal radius fracture. Arch Orthop Trauma Surg 2014; 134: 1775–81.|
|e36.||Sumitani M, Yasunaga H, Uchida K, et al.: Perioperative factors affecting the occurrence of acute complex regional pain syndrome following limb bone fracture surgery: data from the Japanese Diagnosis Procedure Combination database. Rheumatology (Oxford) 2014; 53: 1186–93.|
|e37.||Ortiz-Romero J, Bermudez-Soto I, Torres-González R, Espinoza-Choque F, Zazueta-Hernandez JA, Perez-Atanasio JM: Factors associated with complex regional pain syndrome in surgically treated distal radius fracture. Acta Ortop Bras 2017; 25: 194–6.|
|e38.||Savaş S, İnal EE, Yavuz DD, Uslusoy F, Altuntaş SH, Aydın MA: Risk factors for complex regional pain syndrome in patients with surgically treated traumatic injuries attending hand therapy. J Hand Ther 2017; pii: 0894–1130.|
|e39.||Moseley GL, Herbert RD, Parsons T, Lucas S, Van Hilten JJ, Marinus J: Intense pain soon after wrist fracture strongly predicts who will develop complex regional pain syndrome: prospective cohort study. J Pain 2014; 15: 16–23.|
|e40.||Wertli M, Bachmann LM, Weiner SS, Brunner F: Prognostic factors in complex regional pain syndrome 1: a systematic review. J Rehabil Med 2013; 45: 225–31.|
|e41.||Su YC, Guo YH, Hsieh PC, Lin YC: A meta-analysis and meta-regression of frequency and risk factors for poststroke complex regional pain syndrome. Medicina (Kaunas) 2021; 57: 1232.|
|e42.||Farzad M, Layeghi F, Hosseini A, et al.: Investigate the effect of psychological factors in development of complex regional pain syndrome type I in patients with fracture of the distal radius: a prospective study. J Hand Surg Asian Pac Vol 2018; 23: 554–61.|
|e43.||Berry JD, Rowbotham MC, Petersen KL: Complex regional pain syndrome-like symptoms during herpes zoster. Pain 2004; 110: 8–9.|
|e44.||Richards S, Chalkiadis G, Lakshman R, Buttery JP, Crawford NW: Complex regional pain syndrome following immunisation. Arch Dis Child 2012; 97: 913–5.|
|e45.||Goenka A, Aziz M, Riley P, Vassallo G: Complex regional pain syndrome involving the face following snowball injury. Eur J Pediatr 2014; 173: 397–400.|
|e46.||Oh SW, Choi SU, Park M, Shin JH: Validity of the Budapest criteria for poststroke complex regional pain syndrome. Clin J Pain 2019; 35: 831–5.|
|e47.||Chae J: Poststroke complex regional pain syndrome. Top Stroke Rehabil 2010; 17: 151–62.|
|e48.||Kocabas H, Levendoglu F, Ozerbil OM, Yuruten B: Complex regional pain syndrome in stroke patients. Int J Rehabil Res 2007; 30: 33–8.|
|e49.||Pertoldi S, Di Benedetto P: Shoulder-hand syndrome after stroke. A complex regional pain syndrome. Eura Medicophys 2005; 41: 283–92.|
|e50.||Jang SH, Seo YS: Diagnosis of complex regional pain syndrome I following traumatic axonal injury of the corticospinal tract in a patient with mild traumatic brain injury. Diagnostics (Basel) 2020; 10: 95.|
|e51.||Chung HS, Kim SM, Chang MC, et al.: Diagnosis of complex regional pain syndrome type 1 in patients with corticobasal degeneration: a case report. Ann Palliat Med 2021; 10: 5825–30.|
|e52.||Gofiţă CE, Ciurea ME, Dinescu ŞC, et al.: Complex regional pain syndrome as a paraneoplastic disorder associated with metatypical basal cell carcinoma. Rom J Morphol Embryol 2019; 60: 685–9.|
|e53.||de Rooij AM, Perez RS, Huygen FJ, et al.: Spontaneous onset of complex regional pain syndrome. Eur J Pain 2010; 14: 510–3.|
|e54.||Lipman MD, Hess DE, Werner BC, Deal DN: Fibromyalgia as a predictor of complex regional pain syndrome after distal radius fracture. 2019; 14: 516–22.|
|e55.||Crijns TJ, van der Gronde BATD, Ring D, Leung N: Complex regional pain syndrome after distal radius fracture is uncommon and is often associated with fibromyalgia. Clin Orthop Relat Res 2018; 476: 744–50.|
|e56.||Peterlin BL, Rosso AL, Nair S, Young WB, Schwartzman RJ: Migraine may be a risk factor for the development of complex regional pain syndrome. Cephalalgia 2010; 30: 214–23.|
|e57.||de Mos M, Huygen FJ, Dieleman JP, Koopman JS, Stricker BH, Sturkenboom MC: Medical history and the onset of complex regional pain syndrome (CRPS). Pain 2009; 139: 458–66.|
|e58.||Beerthuizen A, van‘t Spijker A, Huygen FJ, Klein J, de Wit R: Is there an association between psychological factors and the complex regional pain syndrome type 1 (CRPS1) in adults? A systematic review. Pain 2009; 145: 52–9.|
|e59.||Huge V, Lauchart M, Magerl W, et al.: Complex interaction of sensory and motor signs and symptoms in chronic CRPS. PLoS One 2011; 6: e18775.|
|e60.||Dilek B, Yemez B, Kizil R, et al.: Anxious personality is a risk factor for developing complex regional pain syndrome type I. Rheumatol Int 2012; 32: 915–20.|
|e61.||Bean DJ, Johnson MH, Heiss-Dunlop W, Lee AC, Kydd RR: Do psychological factors influence recovery from complex regional pain syndrome type 1? A prospective study. Pain 2015; 156: 2310–8.|
|e62.||Farzad M, MacDermid JC, Packham T, Khodabandeh B, Vahedi M, Shafiee E: Factors associated with disability and pain intensity in patients with complex regional pain syndrome. Disabil Rehabil 2021: 1–9.|
|e63.||Antunovich DR, Horne JC, Tuck NL, Bean DJ: Are illness perceptions associated with pain and disability in complex regional pain syndrome? A cross-sectional study. Pain Med 2021; 22: 100–11.|
|e64.||Beerthuizen A, Stronks DL, Huygen FJ, Passchier J, Klein J, Spijker AV: The association between psychological factors and the development of complex regional pain syndrome type 1 (CRPS1)—a prospective multicenter study. Eur J Pain 2011; 15: 971–5.|
|e65.||Lohnberg JA, Altmaier EM: A review of psychosocial factors in complex regional pain syndrome. J Clin Psychol Med Settings 2013; 20: 247–54.|
|e66.||Park HY, Jang YE, Oh S, Lee PB: Psychological characteristics in patients with chronic complex regional pain syndrome: comparisons with patients with major depressive disorder and other types of chronic pain. J Pain Res 2020; 13: 389–98.|
|e67.||Melis M, Zawawi K, al-Badawi E, Lobo Lobo S, Mehta N: Complex regional pain syndrome in the head and neck: a review of the literature. J Orofac Pain 2002; 16: 93–104.|
|e68.||Parkitny L, Wand BM, Graham C, Quintner J, Moseley G: Interdisciplinary management of complex regional pain syndrome of the face. Phys Ther 2016; 96: 1067–73.|
|e69.||Jokonya L, Mungazi S, Mduluza-Jokonya TL, Kalangu KKN: Truncal complex regional pain syndrome, myth or reality: case report. Int J Surg Case Rep 2021; 83: 105959.|
|e70.||Galer BS, Jensen M: Neglect-like symptoms in complex regional pain syndrome: results of a self-administered survey. J Pain Symptom Manage 1999; 18: 213–7.|
|e71.||Moseley L: Distorted body image in complex regional pain syndrome. Neurology 2005; 65: 773.|
|e72.||Frettlöh J, Hüppe M, Maier C: Severity and specificity of neglect-like symptoms in patients with complex regional pain syndrome (CRPS) compared to chronic limb pain of other origins. Pain 2006; 124: 184–9.|
|e73.||Lewis JS, Kersten P, McCabe CS, McPherson KM, Blake DR: Body perception disturbance: a contribution to pain in complex regional pain syndrome (CRPS). Pain 2007; 133: 111–9.|
|e74.||Bean DJ, Johnson MH, Heiss-Dunlop W, Kydd RR: Extent of recovery in the first 12 months of complex regional pain syndrome type-1: a prospective study. Eur J Pain 2016; 20: 884–94.|
|e75.||Kolb L, Lang C, Seifert F, Maihöfner C: Cognitive correlates of „neglect-like syndrome“ in patients with complex regional pain syndrome. Pain 2012; 153: 1063–73.|
|e76.||Ten Brink AF, Bultitude JH: Predictors of self-reported neglect-like symptoms and involuntary movements in complex regional pain syndrome compared to other chronic limb pain conditions. Pain Med 2021; 22: 2337–49.|
|e77.||Ten Brink AF, Halicka M, Vittersø AD, Jones HG, Stanton TR, Bultitude JH: Validation of the Bath CRPS Body Perception Disturbance Scale. J Pain 2021; 22: 1371–84.|
|e78.||Lewis JS, Kersten P, McPherson KM, et al.: Wherever is my arm? Impaired upper limb position accuracy in complex regional pain syndrome. Pain 2010; 149: 463–9.|
|e79.||Reinersmann A, Landwehrt J, Krumova EK, Ocklenburg S, Güntürkün O, Maier C: Impaired spatial body representation in complex regional pain syndrome type 1 (CRPS I). Pain 2012; 153: 2174–81.|
|e80.||Lewis JS, McCabe C: Body perception disturbance (BPD) in CRPS. Pract Pain Manag 2010; 10: 60–6.|
|e81.||Wittayer M, Dimova V, Birklein F, Schlereth T: Correlates and importance of neglect-like symptoms in complex regional pain syndrome. Pain 2018; 159: 978–86.|
|e82.||Michal M, Adler J, Reiner I, et al.: Association of neglect-like symptoms with anxiety, somatization, and depersonalization in complex regional pain syndrome. Pain Med 2017; 18: 764–72.|
|e83.||Margalit D, Ben Har L, Brill S, Vatine JJ: Complex regional pain syndrome, alexithymia, and psychological distress. J Psychosom Res 2014; 77: 273–7.|
|e84.||Kuttikat A, Shaikh M, Oomatia A, Parker R, Shenker N: Novel signs and their clinical utility in diagnosing complex regional pain syndrome (CRPS): a prospective observational cohort study. Clin J Pain 2017; 33: 496–502.|
|e85.||Förderreuther S, Sailer U, and Straube A: Impaired self-perception of the hand in complex regional pain syndrome (CRPS). Pain 2004; 110: 756–61.|
|e86.||Reinersmann A, Haarmeyer GS, Blankenburg M, et al.: Left is where the L is right. Significantly delayed reaction time in limb laterality recognition in both CRPS and phantom limb pain patients. Neurosci Lett 2010; 486: 240–5.|
|e87.||Peltz E, Seifert F, Lanz S, Müller R, Maihöfner C: Impaired hand size estimation in CRPS. J Pain 2011; 12: 1095–101.|
|e88.||Moseley GL, Zalucki N, Birklein F, Marinus J, van Hilten JJ, Luomajoki H: Thinking about movement hurts: the effect of motor imagery on pain and swelling in people with chronic arm pain. Arthritis Rheum 2008; 59: 623–31.|
|e89.||Echalier A, Borg C, Creac‘h C, Laurent B, Michael GA: Spontaneous sensations reveal distorted body perception in complex regional pain syndrome (CRPS). Brain Cogn 2020; 142: 105568.|
|e90.||Vittersø AD, Buckingham G, Halicka M, Proulx MJ, Bultitude JH: Altered updating of bodily and spatial representations after tool-use in complex regional pain syndrome. Pain 2020; 161: 1609–28.|
|e91.||Brown CA, Scholtes I, Shenker N, Lee MC: Suboptimal learning of tactile-spatial predictions in patients with complex regional pain syndrome. Pain 2020; 161: 369–-78.|
|e92.||Kim J, Kang I, Chung YA, et al.: Altered attentional control over the salience network in complex regional pain syndrome. Sci Rep 2018; 8: 7466.|
|e93.||Christophe L, Delporte L, Revol P, et al.: Complex regional pain syndrome associated with hyperattention rather than neglect for the healthy side: a comprehensive case study. Ann Phys Rehabil Med 2016; 59: 294–301.|
|e94.||Halicka M, Vittersø AD, Proulx MJ, Bultitude JH: Attention upturned: bias toward and away from the affected side of the body and near space in a case of complex regional pain syndrome. Neuropsychologia 2021; 163: 108079.|
|e95.||Mainka T, Bischoff FS, Baron R, et al.: Comparison of muscle and joint pressure-pain thresholds in patients with complex regional pain syndrome and upper limb pain of other origin. Pain 2014; 155: 591–7.|
|e96.||Moseley GL, Gallace A, Di Pietro F, Spence C, Iannetti GD: Limb-specific autonomic dysfunction in complex regional pain syndrome modulated by wearing prism glasses. Pain 2013; 154: 2463–8.|
|e97.||Bartur G, Vatine JJ, Raphaely-Beer N, Peleg S, Katz-Leurer M: Heart rate autonomic regulation system at rest and during paced breathing among patients with CRPS as compared to age-matched healthy controls. Pain Med 2014; 15: 1569–74.|
|e98.||Cohen HE, Hall J, Harris N, McCabe CS, Blake DR, Janig W: Enhanced pain and autonomic responses to ambiguous visual stimuli in chronic complex regional pain syndrome (CRPS) type I. Eur J Pain 2012; 16: 182–95.|
|e99.||Terkelsen AJ, Mølgaard H, Hansen J, Finnerup NB, Krøner K, Jensen TS: Heart rate variability in complex regional pain syndrome during rest and mental and orthostatic stress. Anesthesiology 2012; 116: 133–46.|
|e100.||Schürmann M, Gradl G, Zaspel J, Kayser M, Löhr P, Andress HJ: Peripheral sympathetic function as a predictor of complex regional pain syndrome type I (CRPS I) in patients with radial fracture. Auton Neurosci 2000; 86: 127–34.|
|e101.||Alam OH, Zaidi B, Pierce J, et al.: Phenotypic features of patients with complex regional pain syndrome compared with those with neuropathic pain. Reg Anesth Pain Med 2019: rapm-2019–100511.|
|e102.||Dietz C, Reinhold AK, Escolano-Lozano F, et al.: Complex regional pain syndrome: role of contralateral sensitisation. Br J Anaesth 2021; 127: e1–e3.|
|e103.||Enax-Krumova EK, Baron R, Treede RD, Vollert J: Contralateral sensitisation is not specific for complex regional pain syndrome. Comment on Br J Anaesth 2021; 127: e1–3. Br J Anaesth 2021; 127: e173–e6.|
|e104.||Marinus J, Van Hilten JJ: Clinical expression profiles of complex regional pain syndrome, fibromyalgia and a-specific repetitive strain injury: more common denominators than pain? Disabil Rehabil 2006; 28: 351–62.|
|e105.||van Rooijen DE, Marinus J, van Hilten JJ: Muscle hyperalgesia is widespread in patients with complex regional pain syndrome. Pain 2013; 154: 2745–9.|
|e106.||Birley T, Goebel A: Widespread pain in patients with complex regional pain syndrome. Pain Pract 2014; 14: 526–31.|
|e107.||Martínez-Lavín M, Vargas A, Silveira LH, Amezcua-Guerra LM, Martínez-Martínez LA, Pineda C: Complex regional pain syndrome evolving to full-blown fibromyalgia: a proposal of common mechanisms. J Clin Rheumatol 2021; 27: 274–7.|
|e108.||Bean DJ, Johnson MH, Kydd RR: Relationships between psychological factors, pain, and disability in complex regional pain syndrome and low back pain. Clin J Pain 2014; 30: 647–53.|
|e109.||Munts AG, Van Rootselaar AF, Van Der Meer JN, Koelman JH, Van Hilten JJ, Tijssen MA: Clinical and neurophysiological characterization of myoclonus in complex regional pain syndrome. Mov Disord 2008; 23: 581–7.|
|e110.||Lang AE, Angel M, Bhatia K, et al.: Myoclonus in complex regional pain syndrome. Mov Disord 2009; 24: 314–6; author reply 316.|
|e111.||Schrag A, Trimble M, Quinn N, Bhatia K: The syndrome of fixed dystonia: an evaluation of 103 patients. Brain 2004; 127: 2360–72.|
|e112.||Singh D: Functional dystonia: a pitfall for the foot and ankle surgeon. Foot Ankle Surg 2022; 28: 691–6.|
|e113.||Gray J, Welck M, Cullen NP, Singh D: Functional dystonia in the foot and ankle. Bone Joint J 2021; 103-B: 1127–32.|
|e114.||Simmons BP, Vasile RG: The clenched fist syndrome. J Hand Surg Am 1980; 5: 420–7.|
|e115.||Gradl G, Steinborn M, Wizgall I, Mittlmeier T, Schurmann M: Das akute CRPS I (Morbus Sudeck) nach distaler Radiusfraktur—Methoden der Frühdiagnostik. Zentralbl Chir 2003; 128: 1020–6.|
|e116.||Agten CA, Kobe A, Barnaure I, Galley J, Pfirrmann CW, Brunner F: MRI of complex regional pain syndrome in the foot. Eur J Radiol 2020; 129: 109044.|
|e117.||Graif M, Schweitzer ME, Marks B, Matteucci T, Mandel S: Synovial effusion in reflex sympathetic dystrophy: an additional sign for diagnosis and staging. Skeletal Radiol 1998; 27: 262–5.|
|e118.||Schürmann M, Zaspel J, Löhr P, et al.: Imaging in early posttraumatic complex regional pain syndrome: a comparison of diagnostic methods. Clin J Pain 2007; 23: 449–57.|
|e119.||Wüppenhorst N, Maier C, Frettlöh J, Pennekamp W, Nicolas V: Sensitivity and specificity of 3-phase bone scintigraphy in the diagnosis of complex regional pain syndrome of the upper extremity. Clin J Pain 2010; 26: 182–9.|
|e120.||Cheon M, Kang HJ, Do KH, Yang HS, Han EJ, Yoo J: Diagnostic performance of three-phase bone scintigraphy and digital infrared thermography imaging for chronic post-traumatic complex regional pain syndrome. Diagnostics (Basel) 2021; 11: 1459.|
|e121.||Wertli MM, Brunner F, Steurer J, Held U: Usefulness of bone scintigraphy for the diagnosis of complex regional pain syndrome 1: a systematic review and Bayesian meta-analysis. PLoS One 2017; 12: e0173688.|
|e122.||Wasner G, Schattschneider J, Baron R: Skin temperature side differences—a diagnostic tool for CRPS? Pain 2002; 98: 19–26.|
|e123.||Krumova EK, Frettlöh J, Klauenberg S, Richter H, Wasner G, Maier C: Long-term skin temperature measurements—a practical diagnostic tool in complex regional pain syndrome. Pain 2008; 140: 8–22.|
|e124.||Packham T, MacDermid J, Bain J, Buckley N: Identification of complex regional pain syndrome in the upper limb: skin temperature asymmetry after cold pressor test. Can J Pain 2018; 2: 248–57.|
|e125.||Dietz C, Müller M, Reinhold AK, et al.: What is normal trauma healing and what is complex regional pain syndrome I? An analysis of clinical and experimental biomarkers. Pain 2019; 160: 2278–89.|
|e126.||Krämer HH, Hofbauer LC, Szalay G, et al.: Osteoprotegerin: a new biomarker for impaired bone metabolism in complex regional pain syndrome? Pain 2014; 155: 889–95.|
|e127.||Bruehl S, Harden RN, Galer BS, Saltz S, Backonja M, Stanton-Hicks M: Complex regional pain syndrome: are there distinct subtypes and sequential stages of the syndrome? Pain 2002; 95: 119–24.|
|e128.||Bruehl S, Maihöfner C, Stanton-Hicks M, et al.: Complex regional pain syndrome: evidence for warm and cold subtypes in a large prospective clinical sample. Pain 2016; 157: 1674–81.|
|e129.||Vaneker M, Wilder-Smith OH, Schrombges P, de Man-Hermsen I, Oerlemans HM: 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. Pain 2005; 115: 204–11.|
|e130.||Bean DJ, Johnson MH, Kydd RR: The outcome of complex regional pain syndrome type 1: a systematic review. J Pain 2014; 15: 677–90.|
|e131.||Brunner F, Bachmann LM, Perez RSGM, Marinus J, Wertli MM: Painful swelling after a noxious event and the development of complex regional pain syndrome 1: a one-year prospective study. Eur J Pain 2017; 21: 1611–7.|
|e132.||Llewellyn A, McCabe CS, Hibberd Y, et al.: Are you better? A multi-centre study of patient-defined recovery from complex regional pain syndrome. Eur J Pain 2018; 22: 551–64.|
|e133.||van Rijn MA, Marinus J, Putter H, Bosselaar SR, Moseley GL, van Hilten JJ: Spreading of complex regional pain syndrome: not a random process. J Neural Transm (Vienna) 2011; 118: 1301–9.|
|e134.||Maleki J, LeBel AA, Bennett GJ, Schwartzman RJ: Patterns of spread in complex regional pain syndrome, type I (reflex sympathetic dystrophy). Pain 2000; 88: 259–66.|
|e135.||Enax-Krumova E, Tegenthoff M: Diagnosesicherung bei der Begutachtung des komplexen regionalen Schmerzsyndroms (CRPS). Med Sach 2017; 113: 222–5.|
|e136.||Lunden LK, Jorum E: The challenge of recognizing severe pain and autonomic abnormalities for early diagnosis of CRPS. Scand J Pain 2021; 21: 548–59.|
|e137.||Mailis-Gagnon A, Lakha SF, Allen MD, Deshpande A, Harden RN: Characteristics of complex regional pain syndrome in patients referred to a tertiary pain clinic by community physicians, assessed by the Budapest clinical diagnostic criteria. Pain Med 2014; 15: 1965–74.|
|e138.||Del Piñal F: Editorial. I have a dream ... reflex sympathetic dystrophy (RSD or Complex Regional Pain Syndrome—CRPS I) does not exist. J Hand Surg Eur Vol 2013; 38: 595–7.|
|e139.||Borchers AT, Gershwin ME: The clinical relevance of complex regional pain syndrome type I: the emperor‘s new clothes. Autoimmun Rev 2017; 16: 22–33.|
|e140.||Mailis-Gagnon A, Nicholson K, Blumberger D, Zurowski M: Characteristics and period prevalence of self-induced disorder in patients referred to a pain clinic with the diagnosis of complex regional pain syndrome. Clin J Pain 2008; 24: 176–85.|
|e141.||Secrétan H: Oedème dure et hyperplasie traumatique du métacarpe dorsal. Rev Med Suisse Rom 1901; 21: 409.|
|e142.||Reading G: Secretan‘s syndrome: hard edema of the dorsum of the hand. Plast Reconstruct Surg 1980; 65: 182–7.|
|e143.||Bass C, Yates G: Complex regional pain syndrome type 1 in the medico-legal setting: high rates of somatoform disorders, opiate use and diagnostic uncertainty. Med Sci Law 2018; 58: 147–55.|
|e144.||Wehking E: Das komplexe regionale Schmerzsyndrom (CRPS) in Abgrenzung psychogener Störungen. Versicherungsmedizin 2007; 59: 16–9.|
|e145.||Ochoa JL, Verdugo RJ: Neuropathic pain syndrome displayed by malingerers. J Neuropsychiatry Clin Neurosci 2010; 22: 278–86.|
|e146.||2k-Leitlinie Ärztliche Begutachtung von Menschen mit chronischen Schmerzen (Leitlinie Schmerzbegutachtung). https://www.awmf.org/leitlinien/detail/ll/094-003.html (last accessed on 17 August 2022).|
|e147.||Simmel S, Papenhoff MC, Reimertz C, AG Rehabilitation der BG Kliniken, AG Schmerzmedizin der BG Kliniken: Stufenmodell der Schmerzrehabilitation in den BG Kliniken. Trauma Berufskrankh 2019; 21: 193–8.|
|e148.||S3-Leitlinie Behandlung akuter perioperativer und posttraumatischer Schmerzen. https://www.awmf.org/leitlinien/detail/anmeldung/1/ll/001-025.html (last accessed on 10 August 2022).|
|e149.||Akoglu G, Emre S, Metin A, Bozkurt M: High frequency of hypertrichosis after cast application. Dermatology 2012; 225: 70–4.|
|e150.||Terkelsen AJ, Bach FW, Jensen TS: Experimental forearm immobilization in humans induces cold and mechanical hyperalgesia. Anesthesiology 2008; 109: 297–307.|
|e151.||Singh HP, Davis TR: The effect of short-term dependency and immobility on skin temperature and colour in the hand. J Hand Surg Br 2006; 31: 611–5.|
|e152.||Gillespie S, Cowell F, Cheung GC, Brown DJ: Can we reduce the incidence of complex regional pain syndrome type I in distal radius fractures? The Liverpool experience. Hand Ther 2016; 21: 123–30.|
|e153.||Boersma EZ, Meent HV, Klomp FP, Frölke JM, Nijhuis-van der Sanden MWG, Edwards MJR: Treatment of distal radius fracture: does early activity postinjury lead to a lower incidence of complex regional pain syndrome? Hand (N Y) 2022; 17: 119–27.|
|e154.||Dilek B, Ayhan C, Yagci G, Yakut Y: Effectiveness of the graded motor imagery to improve hand function in patients with distal radius fracture: a randomized controlled trial. J Hand Ther 2018; 31: 2–9.|
|e155.||Hung KC, Chiang MH, Wu SC, et al.: A meta-analysis of randomized clinical trials on the impact of oral vitamin C supplementation on first-year outcomes in orthopedic patients. Sci Rep 2021; 11: 9225.|
|e156.||Seth I, Bulloch G, Seth N, et al: Effect of perioperative vitamin C on the incidence of complex regional pain syndrome: a systematic review and meta-analysis. J Foot Ankle Surg 2022; 61: 748–54.|
|e157.||McCormick ZL, Gagnon CM, Caldwell M, et al.: Short-term functional, emotional, and pain outcomes of patients with complex regional pain syndrome treated in a comprehensive interdisciplinary pain management program. Pain Med 2015; 16: 2357–67.|
|e158.||Lewis JS, Kellett S, McCullough R, et al.: Body perception disturbance and pain reduction in longstanding complex regional pain syndrome following a multidisciplinary rehabilitation program. Pain Med 2019; 20: 2213–9.|
|e159.||Bruehl S, Chung OY: Psychological and behavioral aspects of complex regional pain syndrome management. Clin J Pain 2006; 22: 430–7.|
|e160.||Elomaa M, Hotta J, de C Williams AC, et al.: Symptom reduction and improved function in chronic CRPS type 1 after 12-week integrated, interdisciplinary therapy. Scand J Pain 2019; 19: 257–70.|
|e161.||Kotsougiani-Fischer D, Choi JS, Oh-Fischer JS, et al.: ICF-based multidisciplinary rehabilitation program for complex regional pain syndrome of the hand: efficacy, long-term outcomes, and impact of therapy duration. BMC Surg 2020; 20: 306.|
|e162.||Raqué J, Chung BY, Benrath J: Wirksamkeit einer interdisziplinären multimodalen stationären Schmerztherapie (IMST) bei Patienten mit komplexem regionalem Schmerzsyndrom (CRPS). Eine retrospektive Studie. Schmerz 2022; 36: 81–8.|
|e163.||Oerlemans HM, Oostendorp RA, de Boo T, Goris RJ: Pain and reduced mobility in complex regional pain syndrome I: outcome of a prospective randomised controlled clinical trial of adjuvant physical therapy versus occupational therapy. Pain 1999; 83: 77–83.|
|e164.||Oerlemans H, Goris J, de Boo T, Oostendorp R: Do physical therapy and occupational therapy reduce the impairment percentage in reflex sympathetic dystrophy? Am J Phys Med Rehabil 1999; 78: 533–9.|
|e165.||McCabe C, Haigh R, Ring E, Halligan P, Wall P, Blake D: A controlled pilot study of the utility of mirror visual feedback in the treatment of complex regional pain syndrome (type 1). Rheumatology (Oxford) 2002; 42: 97–101.|
|e166.||Moseley GL: Graded motor imagery is effective for longstanding complex regional pain syndrome: a randomised controlled trial. Pain 2004; 108: 192–8.|
|e167.||Moseley GL: Graded motor imagery for pathologic pain: a randomized controlled trial. Neurology 2006; 67: 2129–34.|
|e168.||Cacchio A, De Blasis E, Necozione S, di Orio F, Santilli V: Mirror therapy for chronic complex regional pain syndrome type 1 and stroke. N Engl Med 2009; 361: 634–6.|
|e169.||Johnson S, Hall J, Barnett S, et al.: Using graded motor imagery for complex regional pain syndrome in clinical practice: failure to improve pain. Eur J Pain 2012; 16: 550–-61.|
|e170.||McCabe C: Mirror visual feedback therapy. A practical approach. J Hand Ther 2011; 24: 170–8.|
|e171.||Storz C, Kraft E: Ergotherapie bei Komplexem regionalen Schmerzsyndrom. Schmerz 2021; 35: 285–93.|
|e172.||Cuenca-Martínez F, Reina-Varona Á, Castillo-García J, et al.: Pain relief by movement representation strategies: an umbrella and mapping review with metameta-analysis of motor imagery, action observation and mirror therapy. Eur J Pain 2022; 26: 284– 309.|
|e173.||O’Neil O, Fernandez MM, Herzog J, et al.: Virtual reality for neurorehabilitation: insights from 3 European clinics. PM R 2018; 10: S198–206.|
|e174.||Kraft E, Azad SC: Exergames—eine neue Therapieoption bei CRPS? Schmerz 2020; 34: 113–4.|
|e175.||Noigroup: Recognize app. www.noigroup.com/product/recogniseapp/ (last accessed on 20 August 2022).|
|e176.||Reflex Pain Management. www.reflexpainmanagement.com/index.php?main_page=document_general_info&cPath=81&products_ id=220 (last accessed on 20 August 2022).|
|e177.||Graded Motor Imagery. www.gradedmotorimagery.com/index.html (last accessed on 20 August 2022).|
|e178.||Turton AJ, Palmer M, Grieve S, et al.: Evaluation of a prototype tool for communicating body perception disturbances in complex regional pain syndrome. Front Hum Neurosci 2013; 7: 517–23.|
|e179.||Wiederhold BK, Gao K, Sulea C, Wiederhold MD: Virtual reality as a distraction technique in chronic pain patients. Cyberpsychol Behav Soc Netw 2014; 17: 346–52|
|e180.||Triberti S, Repetto C, Riva G: Psychological factors influencing the effectiveness of virtual reality–based analgesia: a systematic review. Cyberpsychol Behav Soc Netw 2014; 17: 335–45.|
|e181.||Hwang H, Cho S, Lee JH: The effect of virtual body swapping with mental rehearsal on pain intensity and body perception disturbance in complex regional pain syndrome. Int J Rehabil Res 2014; 37: 167–72.|
|e182.||de Jong JR, Vlaeyen JW, Onghena P, Cuypers C, den Hollander M, Ruijgrok J: Reduction of pain-related fear in complex regional pain syndrome type I: the application of graded exposure in vivo. Pain 2005; 116: 264–75.|
|e183.||Ek JW, van Gijn JC, Samwel H, van Egmond J, Klomp FP, van Dongen RT: Pain exposure physical therapy may be a safe and effective treatment for longstanding complex regional pain syndrome type 1: a case series. Clin Rehabil 2009; 23: 1059–66.|
|e184.||Barnhoorn KJ, van de Meent H, van Dongen RT, et al.: Pain exposure physical therapy (PEPT) compared to conventional treatment in complex regional pain syndrome type 1: a randomised controlled trial. BMJ Open 2015; 5: e008283.|
|e185.||den Hollander M, Goossens M, de Jong J, et al.: Expose or protect? A randomized controlled trial of exposure in vivo vs pain-contingent treatment as usual in patients with complex regional pain syndrome type 1. Pain 2016; 157: 2318–29.|
|e186.||Thomson L: Hypnotherapy for complex regional pain syndrome. Am J Clin Hypn 2022; 64: 195–205.|
|e187.||Lebon J, Rongières M, Apredoaei C, Delclaux S, Mansat P: Physical therapy under hypnosis for the treatment of patients with type 1 complex regional pain syndrome of the hand and wrist: retrospective study of 20 cases. Hand Surg Rehabil 2017; 36: 215–21.|
|e188.||McKittrick ML, Connors EL, McKernan LC: Hypnosis for chronic neuropathic pain: a scoping review. Pain Med 2022; 23: 1015–26.|
|e189.||Flor H, Fydrich T, Turk DC: Efficacy of multidisciplinary pain treatment centers: a meta-analytic review. Pain 1992; 49: 221–30.|
|e190.||Flor H, Turk DC: Chronic pain: an integrated biobehavioral approach. Seattle/WA: IASP Press 2011.|
|e191.||Heutink M, Post MWM, Bongers-Janssen HMH, et al.: The CONECSI trial: results of a randomized controlled trial of a multidisciplinary cognitive behavioral program for coping with chronic neuropathic pain after spinal cord injury. Pain 2012; 153: 120–8.|
|e192.||Williams ACC, Fisher E, Hearn L, Eccleston C: Psychological therapies for the management of chronic pain (excluding headache) in adults. Cochrane Database Syst Rev 2020; 8: CD007407.|
|e193.||S3-Leitlinie Langzeitanwendung von Opioiden bei chronischen nicht-tumorbedingten Schmerzen (LONTS). https://www.awmf.org/leitlinien/detail/ll/145-003.html (last accessed on 17 August 2022).|
|e194.||Kwak SG, Choo YJ, Chang MC: Effectiveness of prednisolone in complex regional pain syndrome treatment: a systematic narrative review. Pain Pract 2022; 22: 381–90.|
|e195.||van den Berg C, de Bree PN, Huygen FJPM, Tiemensma J: Glucocorticoid treatment in patients with complex regional pain syndrome: a systematic review. Eur J Pain 2022; 26: 2009–35.|
|e196.||Varenna M, Braga V, Gatti D: Intramuscular neridronate for the treatment of complex regional pain syndrome type 1: a randomized, double-blind, placebo-controlled study. Ther Adv Musculoskelet Dis 2021; 13: 1759720X211014020.|
|e197.||van de Vusse AC, Stomp-van den Berg SG, Kessels AH, Weber WE: Randomised controlled trial of gabapentin in complex regional pain syndrome type 1. BMC Neurol 2014; 4: 13.|
|e198.||Sigtermans MJ, van Hilten JJ, Bauer MC, et al.: Ketamine produces effective and long-term pain relief in patients with complex regional pain syndrome type 1. Pain 2009; 145: 304–11.|
|e199.||Schwartzman RJ, Alexander GM, Grothusen JR, Paylor T, Reichenberger E, Perreault M: Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study. Pain 2009; 147: 107–15.|
|e200.||Zhao J, Wang Y, Wang D: The effect of ketamine infusion in the treatment of complex regional pain syndrome: a systemic review and meta-analysis. Curr Pain Headache Rep 2018; 22: 12.|
|e201.||Kirkpatrick AF, Saghafi A, Yang K, et al.: Optimizing the treatment of CRPS with ketamine. Clin J Pain 2020; 36: 516–23.|
|e202.||Breuer AJ, Mainka T, Hansel N, Maier C, Krumova EK: Short-term treatment with parecoxib for complex regional pain syndrome: a randomized, placebo-controlled double-blind trial. Pain Physician 2014; 17: 127–37.|
|e203.||Fitzcharles MA, Petzke F, Tölle TR, Häuser W: Cannabis-based medicines and medical cannabis in the treatment of nociplastic pain. Drugs 2021; 81: 2103–16.|
|e204.||Almog S, Aharon-Peretz J, Vulfsons S, et al.: The pharmacokinetics, efficacy, and safety of a novel selective-dose cannabis inhaler in patients with chronic pain: a randomized, double-blinded, placebo-controlled trial. Eur J Pain (United Kingdom) 2020; 24: 1505–16.|
|e205.||Maihöfner C, Schneider S, Bialas P, et al.: Successful treatment of complex regional pain syndrome with topical ambroxol: a case series. Pain Manag 2018; 8: 427–36.|
|e206.||Finch PM, Knudsen L, Drummond PD: Reduction of allodynia in patients with complex regional pain syndrome: a double-blind placebo-controlled trial of topical ketamine. Pain 2009; 146: 18–25.|
|e207.||Ushida T, Tani T, Kanbara T, Zinchuk VS, Kawasaki M, Yamamoto H: Analgesic effects of ketamine ointment in patients with complex regional pain syndrome type 1. Reg Anesth Pain Med 2002; 27: 524–8.|
|e208.||Russo MA, Santarelli DM: A novel compound analgesic cream (ketamine, pentoxifylline, clonidine, DMSO) for complex regional pain syndrome patients. Pain Pract 2016; 16: E14–20.|
|e209.||NICE: Neuropathic pain in adults: pharmacological management in non-specialist settings. London: NICE, 2013. https://www.nice.org.uk/guidance/cg173/resources/neuropathic-pain-in-adults-pharmacological-management-in-nonspecialist-settings-pdf-35109750554053 (last accessed on 22 September 2022).|
|e210.||Finnerup NB, Haroutounian S, Kamerman P, et al.: Neuropathic pain: an updated grading system for research and clinical practice. Pain 2016; 157: 1599–606.|
|e211.||Okumo T, Takayama Y, Maruyama K, Kato M, Sunagawa M: Senso-immunologic prospects for complex regional pain syndrome treatment. Front Immunol 2022; 12: 786511.|
|e212.||Gustin SM, Schwarz A, Birbaumer N, et al.: NMDA-receptor antagonist and morphine decrease CRPS-pain and cerebral pain representation. Pain 2010; 151: 69–76.|
|e213.||Janssen A: Spiegelakupunktur bei komplexem regionalen Schmerzsyndrom (CRPS). Deutsche Zeitschrift für Akupunktur DZA 2020; 63: 96–8.|
|e214.||Bilgili A, Cakır T, Dogan SK, Ercalık T, Filiz MB, Toraman F: The effectiveness of transcutaneous electrical nerve stimulation in the management of patients with complex regional pain syndrome: a randomized, double-blinded, placebo-controlled prospective study. J Back Musculoskelet Rehabil 2016; 21: 661–71.|
|e215.||Li N, Tian F, Wang C, et al.: Therapeutic effect of acupuncture and massage for shoulder-hand syndrome in hemiplegia patients: a clinical two-center randomized controlled trial. J Tradit Chin Med 2012; 32: 343–9.|
|e216.||Korpan MI, Dezu Y, Schneider B, Leitha T, Fialka-Moser V: Acupuncture in the treatment of posttraumatic pain syndrome. Acta Orthop Belg 1999; 65: 197–201.|
|e217.||Wang WY, Wan FM, Ding SQ: [Clinical observation of Jingu three-needle therapy combined with Xingnao Kaiqiao acupuncture on complex regional pain syndrome after stroke]. Zhongguo Zhen Jiu 2019; 39: 1262–6.|
|e218.||S3-Leitlinie „Epidurale Rückenmarkstimulation zur Therapie chronischer Schmerzen“. https://www.awmf.org/leitlinien/detail/ll/008-023.html (last accessed on 22 September 2022).|
|e219.||Deer TR, Levy RM, Kramer J, et al.: Dorsal root ganglion stimulation yielded higher treatment success rate for complex regional pain syndrome and causalgia at 3 and 12 months: a randomized comparative trial. Pain 2017; 158: 669–81.|
|e220.||Hoydonckx Y, Costanzi M, Bhatia A: A scoping review of novel spinal cord stimulation modes for complex regional pain syndrome. Can J Pain 2019; 3: 33–48.|
|e221.||Deer TR, Hunter CW, Mehta P, et al.: A systematic literature review of dorsal root ganglion neurostimulation for the treatment of pain. Pain Med 2020; 21: 1581–9.|
|e222.||Levy RM, Mekhail N, Kramer J, et al.: Therapy habituation at 12 months: spinal cord stimulation versus dorsal root ganglion stimulation for complex regional pain syndrome type I and II. J Pain 2020; 21: 399–408.|
|e223.||D‘Souza RS, Kubrova E, Her YF et al.: Dorsal root ganglion stimulation for lower extremity neuropathic pain syndromes: an evidence-based literature review. Adv Ther 2022; 39: 4440–73.|
|e224.||Canós-Verdecho A, Abejón D, Robledo R, et al.: Randomized prospective study in patients with complex regional pain syndrome of the upper limb with high-frequency spinal cord stimulation (10-kHz) and low-frequency spinal cord stimulation. Neuromodulation 2021; 24: 448–58.|
|e225.||Eitner L, Vollert J, Maier C, Attal N: Botulinumtoxin-A-Injektionen bei neuropathischem Schmerz: Eine Post-hoc-Subgruppenanalyse bei Patienten mit peripherer Nervenverletzung. Schmerz 2017; 31: 524–6.|
|e226.||Park J, Chung ME: Botulinum toxin for central neuropathic pain. Toxins (Basel) 2018; 10: 224.|
|e227.||van Hilten BJ, van de Beek WJ, Hoff JI, Voormolen JH, Delhaas EM: Intrathecal baclofen for the treatment of dystonia in patients with reflex sympathetic dystrophy. N Engl J Med 2000; 343: 625–30.|
|e228.||van Rijn MA, Munts AG, Marinus J, et al.: Intrathecal baclofen for dystonia of complex regional pain syndrome. Pain 2009; 143: 41–7.|
|e229.||Picarelli H, Teixeira MJ, de Andrade DC, et al.: Repetitive transcranial magnetic stimulation is efficacious as an add-on to pharmacological therapy in complex regional pain syndrome (CRPS) type I. J Pain 2010; 11: 1203–10.|
|e230.||Lagueux É, Bernier M, Bourgault P, et al.: The effectiveness of transcranial direct current stimulation as an add-on modality to graded motor imagery for treatment of complex regional pain syndrome: a randomized proof of concept study. Clin J Pain 2018; 34: 145–54.|
|e231.||Nardone R, Brigo F, Höller Y, et al.: Transcranial magnetic stimulation studies in complex regional pain syndrome type I: a review. Acta Neurol Scand 2018; 137: 158–64.|
|e232.||Kiralp MZ, Yildiz S, Vural D, Keskin I, Ay H, Dursun H: Effectiveness of hyperbaric oxygen therapy in the treatment of complex regional pain syndrome. J Int Med Res 2004; 32: 258–62.|
|e233.||O‘Connell NE, Wand BM, Gibson W, Carr DB, Birklein F, Stanton TR: Local anaesthetic sympathetic blockade for complex regional pain syndrome. Cochrane Database Syst Rev 2016; 7: CD004598.|
|e234.||Straube S, Derry S, Moore RA, McQuay HJ: Cervico-thoracic or lumbar sympathectomy for neuropathic pain and complex regional pain syndrome. Cochrane Database Syst Rev 2010; CD002918.|
|e235.||Del Piñal F: Outcomes of carpal tunnel release in complex regional pain syndrome/reflex sympathetic dystrophy/sudeck disease patients. Plast Reconstr Surg 2022; 150: 93–101.|
|e236.||Ayyaswamy B, Saeed B, Anand A, Chan L, Shetty V: Quality of life after amputation in patients with advanced complex regional pain syndrome: a systematic review. EFORT Open Rev 2019; 4: 533–40.|
|e237.||Schrier E, Geertzen JHB, Scheper J, Dijkstra PU: Psychosocial factors associated with poor outcomes after amputation for complex regional pain syndrome type-I. PLoS One 2019; 14: e0213589.|