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Complex regional pain syndrome: an evolving perspective
Abstract
Background: Complex regional pain syndrome (CRPS) is a heterogenous and poorly understood condition that can be provoked by quite minor injuries. The symptoms and signs of CRPS persist, long after the patient has recovered from the inciting event. In some cases, there is a clear association with a peripheral nerve injury. The degree of disability produced by CRPS is often out of proportion to the scale of the original insult and the condition is associated with protracted recovery times and frequent litigation.
Methods: We have performed a PubMed literature search, referenced landmark papers in the field and included a national expert in peripheral nerve injury and repair in our team of authors.
Results and conclusions: The diagnostic criteria for CRPS have changed repeatedly over the last two centuries and much of the historical literature is difficult to compare with more recent research. In this review article, we consider how our understanding of the condition has evolved and discuss its pathogenesis, its apparent heterogenicity and the various investigations and treatments available to the clinician.
... Complex regional pain syndrome [CRPS], also called Sudeck atrophy, often develops in extremities of females from 50 to 70 years of age with the types: 1 (reflex sympathetic dystrophy) without nerve lesions and 2 (causalgia) with a nerve lesion [1][2][3][4][5][6][7][8] . The commonest nerve injuries described in CRPS affect the superficial branch of the radial, the palmar cutaneous branch of the median, and the dorsal branch of the ulnar 6 . ...
... Patients not included in the diagnosis criteria, but with manifestations not explained by another condition can constitute a third type (Not Otherwise Specified, or "NOS") 4,6,8 . Manifestations include allodynia, hyperalgesia, edema, and vascular or motor changes for more than 6 months after causal events like trauma, minor surgery, immobilization, neurological disorders, and myocardial infarction, but the etiology may be unknown [1][2][3][4][5][6][7][8] . CRPS evolves in the stages: acute (up to three months after injury), dystrophic (up to six months after the onset), and atrophic (up about one year after the original injury) 2 . ...
... A small number of cases evolve to a chronic phase, changing the inflammatory to predominant autonomic manifestations involving peripheral and central mechanisms 4 . Multidisciplinary management of CRPS involves physiotherapy, systemic medications, peripheral nerve block, sympathectomy, spinal cord stimulation, and psychotherapy [2][3][4][5][6][7][8] . The CRPS's most common primary causes are fractures (42%), blunt traumatic injuries excluding fractures (21%), surgery (12%), and carpal tunnel syndrome [CTS] (7%) 5,7 . ...
... 3,4 The complex treatment of CRPS includes pharmacotherapy, nerve blocks, physical and psychological measures, and rTMS. 1,5 Despite the ongoing therapy, sometimes, patients still have persistent, burning pain. It leads to the disability of patients and a decrease in the quality of life. ...
... There is then an aberrant response by the body with exaggerated immune response, maladaptive neuroplasticity, and abnormal vasomotor function within the tissues of the affected limb. 5 The International Association for the Study of Pain (IASP) has endorsed the Budapest criteria for the diagnosis of CRPS. CRPS I is not associated with an identifiable nerve injury, whereas CRPS II is associated with a nerve injury. ...
... CRPS I is not associated with an identifiable nerve injury, whereas CRPS II is associated with a nerve injury. 5 Physical and occupational therapy is a critical component of the rehabilitation process in patients with CRPS and is recommended as the first-line treatment. 3 Historically, sympathectomy has been used to treat CRPS. ...
CRPS is a type of severe pain syndrome and can be triggered by previous surgery or trauma. CRPS involves vasomotor changes such as changes in color and temperature of the skin, edema, increased sensitivity to touch, and a limited range of movement. Depending on the presence of nerve damage, CRPS is divided into two types. CRPS type II is associated with a confirmed peripheral nerve injury, while CRPS type I is not associated with an apparent peripheral nerve injury. Despite the ongoing therapy, sometimes, patients still have persistent, burning pain. Intractable CRPS that fail more conservative treatments may undergo neuromodulation. We want to present to your attention a case report of the successful treatment of a patient with CRPS type II using epidural unilateral stimulation. The 44‐year‐old woman came to us with complaints of burning pain and numbness of 1–3 fingers of the right hand, the lateral surface of the right wrist, and lower quarter of the forearm, and shooting pain in the projection of the right median nerve from the shoulder to the wrist. A clinical diagnosis was made—CRPS type II. During the stimulation trial, the most effective pain relief was obtained when the electrode was located in the right side of epidural space at the C4‐Th1 level. The implantation of a pulse generator was performed, and the final selection of the stimulation parameters was carried out (Pulse width: 60 ms, Rate: 210 Hz, and Amplitude: 0.9–1.6 V). The severity of pain syndrome was measured using validated scales in the preoperative period (VAS: 8–9, Pain Detect: 22, NTSS‐9: 4.62, and DN4: 8), in the early postoperative period (VAS: 0–1, Pain Detect: 6, NTSS −9: 0.66, and DN4: 1), and after 12 months (VAS: 0–2, Pain Detect: 6, NTSS‐9: 0.99, and DN4: 1). Observation during 12 months showed that a stable analgesic effect of neurostimulation was achieved using standard neuromodulation regimens and the adaptive stim option. Unilateral stimulation is an effective type of SCS in the treatment of pain syndromes. adaptive stim is usually not applicable for lead implantation at the cervical level. Nevertheless, the rational use of stimulation at threshold values allowed our patient to use adaptive stim in a non‐standard situation.
... 3,4 The complex treatment of CRPS includes pharmacotherapy, nerve blocks, physical and psychological measures, and rTMS. 1,5 Despite the ongoing therapy, sometimes patients still have persistent, burning pain. It leads to the disability of patients and a decrease in the quality of life. ...
... There is then an aberrant response by the body with exaggerated immune response, maladaptive neuroplasticity, and abnormal vasomotor function within the tissues of the affected limb. 5 The International Association for the Study of Pain (IASP) has endorsed the Budapest criteria for the diagnosis of CRPS. CRPS I is not associated with an identifiable nerve injury, whereas CRPS II is associated with a nerve injury. ...
... CRPS I is not associated with an identifiable nerve injury, whereas CRPS II is associated with a nerve injury. 5 Physical and occupational therapy is a critical component of the rehabilitation process in patients with CRPS and is recommended as the first-line treatment. 3 Historically, Sympathectomy has been used to treat CRPS. ...
CRPS is a type of severe pain syndrome and can be triggered by previous surgery or trauma. CRPS type II is associated with a confirmed nerve injury. We want to present to your attention a case report of successful treatment of CRPS type II using unilateral epidural stimulation.
... In 1872, Silas Weir Mitchell coined the term "causalgia" for these findings [1]. By the 1900s, the condition was being studied further and the term "Sudeck's atrophy" was introduced by Nonne, a student of Paul Sudeck, who also defined the forms of the disease [1,2]. ...
... Between 1946-47, James Evans described 57 patients with a history of symptoms and signs he called "Reflex Sympathetic Dystrophy" [1,2]. He hypothesised that an activation of the sympathetic neurons was linked to the condition, and sympathetic blocks re- lieved the symptoms. ...
... He hypothesised that an activation of the sympathetic neurons was linked to the condition, and sympathetic blocks re- lieved the symptoms. It was John Bonica who proposed to rename the disease as "Complex Regional Pain Syndrome" (CRPS) and classified it in the 1950's, and in 1993, the criteria for the diagnosis of CRPS were established as the Orlando criteria [1,2]. ...
... CRPS is a rare condition that was first described in the sixteenth century and renamed as we know it today by the International Association of Study of Pain (IASP) in 1993 (6). It is classified into two main groups: type 1 CRPS, in which there is no physical injury to the nerve involved, and type 2 CRPS, in which there is evident damage to the nerve structure (6)(7)(8). ...
... CRPS is a rare condition that was first described in the sixteenth century and renamed as we know it today by the International Association of Study of Pain (IASP) in 1993 (6). It is classified into two main groups: type 1 CRPS, in which there is no physical injury to the nerve involved, and type 2 CRPS, in which there is evident damage to the nerve structure (6)(7)(8). The case of the patient reported here was classified as type 1 CRPS since she met the Budapest diagnostic criteria (7) and there was no specific neuropathic damage according to clinical, paraclinical, and imaging information. ...
Resumen Introducción. El síndrome de dolor regional complejo (SDRC) es una afección rara cuyo diagnóstico se realiza con base en un examen físico y los síntomas reportados por el paciente ya que no existe una prueba diagnóstica definitiva. El tratamiento de esta condición, que también es limitado y a menudo no produce alivio completo de los síntomas, se centra en aumentar la movilidad y el uso del miembro afectado. Se presenta el caso de una paciente que desarrolló SDRC como consecuencia de una infección por SARS-CoV-2. Dado que hasta el momento no se ha documentado una relación causal entre estas dos entidades, este se considera un caso atípico. Presentación del caso. Mujer de 28 años quien consultó a una institución de cuarto nivel de atención de Bogotá (Colombia) por dolor de características neuropáticas y movilidad limitada del miembro superior izquierdo. Tres semanas antes la paciente había presentado infección por SARS-CoV-2. Dada la sintomatología, se consideró que cursaba con SDRC secundario a infección por SARS-CoV-2. Debido a que los síntomas persistían a pesar del manejo analgésico administrado, se decidió realizar una intervención analgésica invasiva con la cual se logró una mejoría parcial. Conclusiones. Se reporta el caso de una paciente que posterior a una infección por SARS-CoV-2 presentó sintomatología correspondiente al SDRC con una secuencia temporal que permite vincular ambas entidades, configurando así una rara asociación. La información aquí descrita permite establecer un punto de partida para el estudio y el mejor entendimiento de ambas enfermedades teniendo en cuenta sus características y puntos comunes.
... The disorder involves autonomic and inflammatory abnormalities. With CRPS, the afflicted person experiences pain that is greater in magnitude and/or duration than would be typically expected from the surgery or traumatic inciting event (1)(2)(3). The pathophysiologic mechanism underlying CRPS is not fully known, but it is believed that the inciting event-considered an injury-triggers abnormal processes in both the peripheral and central nervous systems, causing dysfunctional neuroplasticity and an excessive immune and inflammatory response (1,(4)(5)(6). ...
... It includes physical therapy; anti-inflammatory, neuropathic (i.e., gabapentin), biophosphonates, the antioxidant ascorbic acid and/or narcotic medication; and sympathetic nerve blocks or continuous regional anesthesia or trigger point injections (1,5,(12)(13)(14). In the late stages, other treat-ments include implantation of a spinal cord stimulator, sympathectomy, or controversially-amputation of the limb (3,(15)(16)(17)(18). In CRPS type 2, where the nerve has been determined, there has been success with targeted nerve procedures such as decompression or denervation (11,(19)(20)(21). ...
Background: Complex regional pain syndrome (CRPS) is a potentially severely painful and debilitating disorder that frequently affects an extremity after surgery or even a minor injury. Treatment of CRPS can be challenging, and due to some patients’ co-morbidities, treatments may be limited. Case Report: Retrospective review of 20 patients who were diagnosed with CRPS of the foot and/or ankle early (within 45 days of onset) and who were adjunctively treated with ring-type ankle blocks of bupivacaine with dexamethasone. Patients who benefited from the treatment were monitored for 12 months. Conclusion: When CRPS of the foot and/or ankle was diagnosed early and adjunctively treated with one or two 2 ankle blocks of bupivacaine with dexamethasone, the condition resolved completely for 18 of the 20 patients (90%). The ankle block is a simple, safe treatment with the potential to assist in alleviating CRPS of the foot and/or ankle when the condition is diagnosed early. Key words: Ankle, ankle block, complex regional pain syndrome (crps), foot, local anesthesia
... En la literatura se ha reportado una prevalencia aproximada de 5,4 a 26,2 por cada 100.000 personas al año, existiendo algunos factores de riesgo definidos como lo son: género femenino, tener una lesión en la extremidad superior, y sufrir un trauma de alta energía [6]. Se han descrito múltiples esquemas de tratamiento que comprenden desde terapia psicológica, terapia ocupacional y medicamentos, hasta la realización de procedimientos intervencionistas que incluyen bloqueos, radiofrecuencia e incluso neuroestimulación [7], [8]. ...
... La fisiopatología del SDRC es compleja y sigue siendo un tema de interés en múltiples estudios a nivel mundial, la evidencia actual sugiere que es una entidad multifactorial que requiere de un detonante inicial para desencadenar la presentación de la misma, se caracteriza por tener una respuesta aberrante a estímulos nocivos que sobrepasan en intensidad lo esperable para la lesión inicial [7], se ha visto que está determinada por tres componentes principales: los cambios inflamatorios, el proceso de sensibilización central y la disfunción vasomotora[1]. ...
... Interestingly, the patient was previously diagnosed with CRPS and EDS, which made the diagnosis of Parsonage-Turner syndrome more challenging as both conditions can cause pain and weakness around the shoulder [3]. Since CRPS is a diagnosis of exclusion, abnormalities on an EMG or nerve conduction study would commonly not be seen [15]. Thus, these tests were critical to differentially diagnose Parsonage-Turner syndrome. ...
Introduction:
Parsonage-Turner syndrome is a rare condition that is often misdiagnosed by physicians due to the overlapping symptoms with other conditions such as rotator cuff injury and cervical radiculopathy. The etiology of the Parsonage-Turner syndrome is unknown, but has been associated with an immune-mediated response to rheumatic disease, infection, surgery, and immunizations.
Case presentation:
A 18-year-old female former tennis player with a history of complex regional pain syndrome (CRPS), Ehler-Danlos syndrome (EDS), and two prior right shoulder surgeries presented to the orthopaedic clinic with bilateral shoulder pain. After a third surgery on the right shoulder, the patient later developed constant burning and sharp pain around the right shoulder that radiated toward the chest. She also experienced numbness, tingling, and weakness in the right shoulder along with pain and weakness in the left shoulder. The patient was tender over the right musculocutaneous nerve and both shoulders were inflamed on ultrasound. Electromyography (EMG) and nerve conduction studies were performed, which were consistent with a bilateral subacute on chronic brachial plexopathy, suggestive of Parsonage-Turner syndrome. Rheumatology was consulted due to an extensive family history of autoimmune diseases, leading to an additional diagnosis of ankylosing spondylitis. The patient's bilateral shoulder pain slowly improved over the following year with physical therapy and prolotherapy treatments.
Conclusion:
The case described, herein, represents a unique patient who presents with the rare conditions of ankylosing spondylitis, CRPS, EDS, and Parsonage-Turner syndrome. EMG was critical to differentiate Parsonage-Turner syndrome from the overlapping CRPS symptoms and without this, the diagnosis of ankylosing spondylitis may have been delayed. It is imperative physicians take a thorough history, include uncommon or rare conditions as a potential diagnosis, and undergo thorough testing while evaluating a patient to avoid unnecessary treatment therapies and patient dissatisfaction.
... The incidence of CRPSI is much higher than CRPSII; A retrospective epidemiological analysis of 1043 CRPS patients reported that the incidence of CRPSI was 88%, and that of CRPSII was 12%. 2 In the 1950s, John Bonica described CRPSI in three stages: acute/early stage, dystrophic stage, and the atrophy/late stage. 3 However, clinical practice has shown that not all CRPSI patients develop sequentially in this staging pattern, and the signs and symptoms of one stage may occur at any other stage. 4 Currently, CRPS is often classified into two subtypes: "cold" and "warm." ...
Complex regional pain syndrome (CRPS) is a chronic pain disorder characterized by spontaneous or evoked regionally-confined pain which is out of proportion to the initial trauma event. The disease can seriously affect the quality of the patients’ life, increase the psychological burden, and cause various degrees of disability. Despite the awareness of CRPS among medical practitioners for over a century, its pathogenesis remains unclear, and the available treatment is still unsatisfactory. Effective animal models are the foundation of disease research, which is helpful in understanding the pathogenesis and an in-depth exploration of the appropriate therapeutic approaches. Currently, researchers have established a series of animal models of the disease. There are four main CRPSI animal models: chronic post-ischemic pain (CPIP) model, tibial fracture/cast immobilization model, passive transfer-trauma model, and the needlestick-nerve-injury (NNI) model. The modeling methods of these models are constantly improving over time. In preclinical studies, the interpretation of experimental results and the horizontal comparison between similar studies may be affected by the nature of the experimental animal breeds, sex, diet, and psychology. There is need to facilitate the choice of appropriate animal models and avoid the interference of the factors influencing animal models on the interpretation of research results. The review will provide a basic overview of the influencing factors, modeling methods, and the characteristics of CRPSI animal models.
... The disturbance of the sympathetic nervous system seems to be involved in CRPS [13] and some symptoms that patients present in the affected limb, such as edema and skin texture or sweating changes, can be compatible with an automatic nervous system dysfunction [2,14,15]. For this reason, achieving the suppression of pain in the early phases of the condition can be very meaningful for many patients [16,17]. ...
Lumbar sympathetic blocks (LSBs) are commonly performed to treat pain ailments in the lower limbs. LSBs involve injecting local anesthetic around the nerves. The injection is guided by fluoroscopy which is sometimes considered to be insufficiently accurate. The main aim was to analyze the plantar foot skin temperature data acquired while performing LSBs in patients with complex regional pain syndrome (CRPS) affecting the lower limbs. Forty-four LSBs for treating lower limb CRPS in 13 patients were assessed. Pain medicine physicians visualized the infrared thermography (IRT) video in real time and classified the performance depending on the observed thermal changes within the first 4 min. Thirty-two percent of the cases did not register temperature variations after lidocaine was injected, requiring the needle to be relocated. Differences between moments are indicated using the 95% confidence intervals of the differences (CI 95%), the Cohen effect size (ES) and the significance (p value). In successful cases, after injecting lidocaine, increases at minute 7 for the mean (CI 95% (1.4, 2.1 °C), p < 0.001 and ES = 0.5), at minute 5 for maximum temperature (CI 95% (2.3, 3.3 °C), p < 0.001 and ES = 0.6) and at minute 6 for SD (CI 95% (0.2, 0.3 °C), p < 0.001 and ES = 0.5) were observed. The results of our preliminary study showed that the measurement of skin temperature in real time by infrared thermography is valuable for assessing the success of lumbar sympathetic blocks.
This review delves into the intricate biological underpinnings of pain perception. It encompasses nociceptive signaling pathways, the molecular mechanisms involved, and the subjective experience of discomfort in humans. The initial focus is on nociceptor transduction, where specialized neurons transform noxious stimuli into electrical impulses. Subsequently, the review explores the central nervous system, elucidating how these signals are processed and modulated by critical elements such as ion channels, receptors, and neurotransmitters (e.g., substance P, glutamate, GABA). Shifting gears toward chronic pain, the review examines the concept of neuroplasticity, highlighting its potential to induce maladaptive responses through alterations in neural networks. The burgeoning field of pain genomics, alongside established genetic research, offers valuable insights that could pave the way for a framework of personalized pain management strategies. Finally, the review emphasizes the significance of these molecular insights in facilitating accurate therapeutic interventions. The overarching objective is to establish an integrative framework for precision medicine in pain management by incorporating this information alongside biopsychosocial models. This framework serves to translate the heterogeneous landscape of pain mechanisms into a coherent roadmap for the development of effective therapies.
Complex Regional Pain Syndrome (CRPS) is a disease that significantly reduces functional ability and is characterized by pronounced, persistent pain, which often affects one limb. Despite advances in research and treatment, CRPS remains a challenge to diagnose and treat effectively. CRPS mostly affects people between the ages of 40 and 60, with a higher prevalence in women. The pathophysiology of CRPS includes a complex interplay of neuroimmunological, neuroplastic and nociceptive mechanisms. CRPS is characterized by a diverse spectrum of clinical manifestations that reflect a complex interaction of sensory, motor, autonomic, and inflammatory processes. The diagnosis of CRPS requires a multimodal approach that integrates clinical evaluation, diagnostic criteria, and additional testing. The Budapest criteria represent standardized diagnostic criteria, including sensory, motor, vasomotor and sudomotor symptoms. The therapeutic approach to CRPS includes a variety of therapeutic modalities aimed at alleviating pain, improving function, and improving quality of life. A multimodal interdisciplinary approach including pharmacological, non-pharmacological and interventional modalities is necessary for comprehensive treatment. Further research is needed to elucidate the underlying mechanisms and optimize therapeutic strategies for patients with CRPS. This review paper aims to provide a thorough analysis of CRPS, incorporating current research findings to advance understanding and inform evidence-based treatment strategies.
Introduction: Complex regional pain syndrome type I (CRPS-I) is a debilitating neuropathic painful condition associated with allodynia, hyperalgesia, sudomotor and/or vasomotor dysfunctions, turning investigation of its pathophysiology and new therapeutic strategies into an essential topic. We aim to investigate the impact of ischemia/reperfusion injury on the immunocontent of CB1 and CB2 cannabinoid receptor isoforms in the paws of mice submitted to a chronic postischemia pain (CPIP) model and the effects of local administration of cannabidiol (CBD) on mechanical hyperalgesia. Methods: Female Swiss mice, 30-35 g, were submitted to the CPIP model on the right hind paw. Skin and muscle samples were removed at different periods for western blot analysis. Results: No changes in the immunocontent of CB1 and CB2 receptors in paw muscle tissues after ischemia-reperfusion were observed. CBD promoted an antihyperalgesic effect in both phases. AM281 reversed the effect of CBD, whereas ruthenium red abolished the late phase. Conclusion: Our results point to the possible beneficial effects of local administration of CBD in modulating CRPS-I in humans. As possible targets for CBD antihyperalgesia in this model, the contribution of cannabinoid receptor CB1, in addition to TRPM8 is suggested.
Complex regional pain syndrome is a rare and not well understood chronic pain condition that can affect anyone, irrespective of age and sex. It is important that nurses and the wider healthcare team are aware of the symptoms and recommended management of this condition, with timely diagnosis and appropriate rehabilitation being particularly important. This article provides an overview of complex regional pain syndrome and explains what is involved in the diagnosis and treatment of this condition. Understanding the complexity of the condition and the relevant management guidelines will enable nurses to provide effective care and support for patients.
Complex regional pain syndrome (CRPS) is a multifactorial pathology characterized by chronic pain, autonomic disorders, and motor dysfunction. This review discusses the mechanisms of CRPS development, as well as methods of its diagnosis, treatment, and prevention. In addition to drug treatment and physical therapy, issues of interventional methods for the treatment of CRPS are also covered. Along with sympathetic blocks and various ablation techniques under ultrasound and fluoroscopic guidance, a new waveform for spinal cord stimulation and new stimulation targets such as dorsal root ganglia have been proposed.
Neuropathic pain (NP) arises from irritation or damage of nociceptive nerve fibers or nociceptive neurons. It is a common form of pain, often poorly responding to analgesic medications. This chapter discusses the pathophysiology and current treatment of three common categories of neuropathic pain and reviews the literature on the efficacy of botulinum neurotoxin (BoNT) therapy in these pain categories. The discussed categories consist of postherpetic neuralgia, posttraumatic neuralgia, and painful diabetic neuropathy. Trigeminal neuralgia, another form of neuropathic pain, is discussed in the chapter on facial pain (Chap. 10); other forms of neuropathic pain such as plantar fasciitis are discussed as individual chapters in this book. Published data from blinded- and placebo-controlled studies indicate that botulinum toxin-A is effective in alleviating pain of postherpetic and posttraumatic neuralgias as well as pain associated with diabetic polyneuropathy. Observations on central neuropathic pain, complex regional pain syndrome, chemotherapy-induced pain, and phantom pain are briefly discussed.
Complex regional pain syndrome (CRPS) is a potentially life-altering, neuropathic pain condition that often affects an extremity in response to surgery or even minor trauma. The pain is often disproportionate to the injury sustained or the surgical procedure performed—and it has been described as excruciating and unbearable. CRPS can result in irreversible, disabling changes in the affected limb. In some cases it has resulted in amputation or severe psychological issues. However, CRPS outcomes are generally more successful with early detection and treatment. This article presents an overview of CRPS and discusses the critical role nurses can play in recognizing the condition early, assisting with treatment, and providing psychological support.
The occurrence of hematoma and bruise formation, accounting for the majority of donation-related complications in the arm, rarely results in complex regional pain syndrome (CRPS). We report a 24-year-old man who presented with CRPS on his right upper limb two months later due to hematoma and bruising formation just after a blood donation following with immediate performance of strenuous exercise in the upper limbs. Triple phase bone scan, one of the bone scintigraphic studies, revealed positive findings and was compatible with the symptoms of CRPS, e.g. hyperalgesia, swelling and discoloration. The potentially disabling condition, however, ended up with a thankfully benign outcome because of our early finding and proper treatment that included three-day oral prednisolone and two-week physiotherapy and occupational rehabilitation. To our knowledge, CRPS produced by donation-related complications with subsequent hematoma and bruise due to vigorous exercise is rare. CRPS should be taken into consideration in a blood donor who demonstrated allodynia because of performing heavy exercise immediately after blood donation.
The majority of included studies (8 out of 11, n = 54) supported the concept of considering amputation for selected, unresponsive cases of complex regional pain syndrome (CRPS) as a justifiable alternative to an unsuccessful multimodality nonoperative option. Of patients who underwent amputation, 66% experienced improvement in quality of life (QOL) and 37% were able to use a prosthesis, 16% had an obvious decline in QOL and for 12% of patients, no clear details were given, although it was suggested by authors that these patients also encountered deterioration after amputation. Complications of phantom limb pain, recurrence of CRPS and stump pain were predominant risks and were noticed in 65%, 45% and 30% of cases after amputation, respectively and two-thirds of patients were satisfied. Amputation can be considered by clinicians and patients as an option to improve QOL and to relieve agonizing, excruciating pain of severe, resistant CRPS at a specialized centre after multidisclipinary involvement but it must be acknowledged that evidence is limited, and the there are risks of aggravating or recurrence of CRPS, phantom pain and unpredictable consequences of rehabilitation. Amputation, if considered for resistant CRPS, should be carried out at specialist centres and after MDT involvement before and after surgery. It should only be considered if requested by patients with poor quality of life who have failed to improve after multiple treatment modalities. Further high quality and comprehensive research is needed to understand the severe form of CRPS which behaves differently form less severe stages.
Cite this article: EFORT Open Rev 2019;4:533-540. DOI: 10.1302/2058-5241.4.190008
Complex Regional Pain Syndrome type 1 (CRPS-1) is a disabling painful disease whose hallmark is pain disproportionate to inciting event. CRPS is also characterized by symptoms and signs, such as vasomotor, sudomotor, trophic and motor changes. Therapeutic approach of CRPS-1 still remains a challenge for clinicians treating a disease with potential heavy consequences on patient prognosis. In the past years, the treatment with bisphosphonates (BPs) has gained some success as confirmed by the results of a number of meta-analyses. The aim of this paper is to point out the pivotal role of bone in CRPS pathogenesis. The efficacy of BPs is likely to be related to bone tissue involvement in the early pathophysiological steps of the disease, as demonstrated by evidences highlighting the central role of bone in the initial phases. Bone can become a source of inflammatory cytokines when triggered by a direct injury. Moreover, peptidergic fibers that innervate both mineralized bone and bone marrow can play a role in triggering or maintaining the microvascular disturbance at bone level. Indeed, bone involvement is consistent with the mineralization disturbance as well as the results of instrumental investigations (e.g., MRI, bone scan). In this regard, an intriguing issue relies on the excellent therapeutic response to BPs treatment of other diseases (e.g., Transient Osteoporosis of the Hip and Regional Migratory Osteoporosis) that share with CRPS-1 some clinical and instrumental features.
Introduction
Complex regional pain syndrome (CRPS) is characterized by searing pain, hyperalgesia, edema, allodynia, and skin changes. CRPS may be difficult to diagnose and to treat given poorly understood mechanisms as well as its presentation of symptoms that may mimic common conditions such as joint stiffness in this condition as well as rheumatoid arthritis.
Case Report
A 71-year-old female presented to our clinic post shingles of the right upper extremity. We diagnosed her with CRPS based on the Budapest diagnostic criteria and the clinical findings of pain and decreased the range of motion along with edema, hypersensitivity, discoloration and allodynia of the right thumb and index finger. She was treated with vitamin C as well as gabapentin and physical therapy. The patient was unable to go consistently to physical therapy due to insurance limitations, and we found no clinical benefit of vitamin C in reducing her symptoms. She was lost to follow-up during her treatment but re-emerged at 21 months. At that time she reported, she was largely unchanged in regards to her right-hand symptoms but did believe the gabapentin was helpful and still continued to take 300 mg daily.
Conclusion
This case report highlights the usefulness of the Budapest diagnostic criteria to make the diagnosis of CRPS when associated with shingles, which can cause long-term pain and mimic some findings. Prompt diagnosis is important, as recovery typically extends beyond 6 months; our patient still reported continued symptoms at 21 months post initial presentation. Our primary treatment plan was physical therapy, which she discontinued due to insurance limitations. We recommend that patients, physicians, and third-party payers work together to extend access to physical therapy. More investigation is warranted regarding symptomatic treatment, as we found limited clinical benefit of gabapentin and vitamin C.
Background:
Complex regional pain syndrome (CRPS) is a painful and disabling condition that usually manifests in response to trauma or surgery. When it occurs, it is associated with significant pain and disability. It is thought to arise and persist as a consequence of a maladaptive pro-inflammatory response and disturbances in sympathetically-mediated vasomotor control, together with maladaptive peripheral and central neuronal plasticity. CRPS can be classified into two types: type I (CRPS I) in which a specific nerve lesion has not been identified, and type II (CRPS II) where there is an identifiable nerve lesion. Guidelines recommend the inclusion of a variety of physiotherapy interventions as part of the multimodal treatment of people with CRPS, although their effectiveness is not known.
Objectives:
To determine the effectiveness of physiotherapy interventions for treating the pain and disability associated with CRPS types I and II.
Search methods:
We searched the following databases from inception up to 12 February 2015: CENTRAL (the Cochrane Library), MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, PEDro, Web of Science, DARE and Health Technology Assessments, without language restrictions, for randomised controlled trials (RCTs) of physiotherapy interventions for treating pain and disability in people CRPS. We also searched additional online sources for unpublished trials and trials in progress.
Selection criteria:
We included RCTs of physiotherapy interventions (including manual therapy, therapeutic exercise, electrotherapy, physiotherapist-administered education and cortically directed sensory-motor rehabilitation strategies) employed in either a stand-alone fashion or in combination, compared with placebo, no treatment, another intervention or usual care, or of varying physiotherapy interventions compared with each other in adults with CRPS I and II. Our primary outcomes of interest were patient-centred outcomes of pain intensity and functional disability.
Data collection and analysis:
Two review authors independently evaluated those studies identified through the electronic searches for eligibility and subsequently extracted all relevant data from the included RCTs. Two review authors independently performed 'Risk of bias' assessments and rated the quality of the body of evidence for the main outcomes using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
Main results:
We included 18 RCTs (739 participants) that tested the effectiveness of a broad range of physiotherapy-based interventions. Overall, there was a paucity of high quality evidence concerning physiotherapy treatment for pain and disability in people with CRPS I. Most included trials were at 'high' risk of bias (15 trials) and the remainder were at 'unclear' risk of bias (three trials). The quality of the evidence was very low or low for all comparisons, according to the GRADE approach.We found very low quality evidence that graded motor imagery (GMI; two trials, 49 participants) may be useful for improving pain (0 to 100 VAS) (mean difference (MD) -21.00, 95% CI -31.17 to -10.83) and functional disability (11-point numerical rating scale) (MD 2.30, 95% CI 1.12 to 3.48), at long-term (six months) follow-up, in people with CRPS I compared to usual care plus physiotherapy; very low quality evidence that multimodal physiotherapy (one trial, 135 participants) may be useful for improving 'impairment' at long-term (12 month) follow-up compared to a minimal 'social work' intervention; and very low quality evidence that mirror therapy (two trials, 72 participants) provides clinically meaningful improvements in pain (0 to 10 VAS) (MD 3.4, 95% CI -4.71 to -2.09) and function (0 to 5 functional ability subscale of the Wolf Motor Function Test) (MD -2.3, 95% CI -2.88 to -1.72) at long-term (six month) follow-up in people with CRPS I post stroke compared to placebo (covered mirror).There was low to very low quality evidence that tactile discrimination training, stellate ganglion block via ultrasound and pulsed electromagnetic field therapy compared to placebo, and manual lymphatic drainage combined with and compared to either anti-inflammatories and physical therapy or exercise are not effective for treating pain in the short-term in people with CRPS I. Laser therapy may provide small clinically insignificant, short-term, improvements in pain compared to interferential current therapy in people with CRPS I.Adverse events were only rarely reported in the included trials. No trials including participants with CRPS II met the inclusion criteria of this review.
Authors' conclusions:
The best available data show that GMI and mirror therapy may provide clinically meaningful improvements in pain and function in people with CRPS I although the quality of the supporting evidence is very low. Evidence of the effectiveness of multimodal physiotherapy, electrotherapy and manual lymphatic drainage for treating people with CRPS types I and II is generally absent or unclear. Large scale, high quality RCTs are required to test the effectiveness of physiotherapy-based interventions for treating pain and disability of people with CRPS I and II. Implications for clinical practice and future research are considered.
Complex regional pain syndrome (CRPS) is a severe chronic pain condition that most often develops following trauma. Some investigators have postulated CRPS to be a post-traumatic neuralgia associated with distal degeneration of small-diameter peripheral axons. Intravenous immunoglobulin treatment (IVIG) has been shown to be efficacious in the treatment of painful polyneuropathies. Some CRPS patients have been reported to respond to IVIG. Based on a recent hypothesis proposing an autoimmune etiology for CRPS, we decided to offer plasma exchange therapy (PE) to CRPS patients with a clinical presentation suggestive of a small fiber neuropathy.
To evaluate the efficacy of PE in a group of CRPS patients with a clinical presentation suggestive of a small fiber neuropathy that were either non-responders or poor responders to their current treatment.
This is a retrospective case series study of CRPS patients that met the Budapest diagnostic criteria for CRPS and received PE as treatment for their illness between September 2012 and June 2014. Approval for this review was granted by the Drexel University Institutional Review Board.
Drexel University College of Medicine pain clinic METHODS: Thirty-three CRPS patients that received PE treatment were retrospectively studied. The workup for these patients consisted of a complete medical and pain evaluation, the completion of the short-form McGill questionnaire, quantitative sensory testing (QST), and skin punch biopsy. The PE protocol was as follows: all patients had a series of PE therapies (range 5 to 11 with a mean of 7.2) performed over a 2 to 3 week period. Following the PE series, the patients had a pain evaluation and completed the short-form McGill questionnaire. Patients that responded to PE were offered maintenance therapy consisting of either weekly PE or other immune modulating agents. In these patients, their pain was evaluated during the maintenance phase.
Thirty of the 33 patients demonstrated significant (P < 0.01) median pain reduction of 64% following the initial series of PE. Three patients demonstrated no improvement. Twenty-four patients are receiving maintenance therapy, the pain reduction in these patients following the initial PE series has been maintained with either weekly PE (n = 15), oral immune modulating agents (n = 8), or IVIG (n = 1). The remaining 6 patients are not receiving maintenance therapy and their pain has returned to pre-treatment levels. In addition, this study suggests that patients with the greatest loss of small fibers and the greatest temperature sensory deficits are most likey to benefit from PE therapy.
The major limitation of this study is its retrospective nature which includes non-randomization, non-blinding, and an uncontrolled design.
This study shows that PE is effective in a subset of patients with severe long-standing CRPS and that the reduction in pain following the initial series of PE treatments can be maintained on a weekly PE schedule, IVIG, or with other immune modulating drugs. Large, randomized, placebo controlled studies may be required to confirm and expand these results. Such studies may lead to new therapies for this severe life-altering condition.
Complex regional pain syndrome, small fiber neuropathy, plasma exchange, skin punch biopsies, immune modulating therapies.
This is a reprint of a Cochrane protocol, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2013, Issue 12 http://www.thecochranelibrary.com Buprenorphine for treating cancer pain (Protocol)
There is currently no strong consensus regarding the optimal management of complex regional pain syndrome although a multitude of interventions have been described and are commonly used.
To summarise the evidence from Cochrane and non-Cochrane systematic reviews of the effectiveness of any therapeutic intervention used to reduce pain, disability or both in adults with complex regional pain syndrome (CRPS).
We identified Cochrane reviews and non-Cochrane reviews through a systematic search of the following databases: Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), Ovid MEDLINE, Ovid EMBASE, CINAHL, LILACS and PEDro. We included non-Cochrane systematic reviews where they contained evidence not covered by identified Cochrane reviews. The methodological quality of reviews was assessed using the AMSTAR tool.We extracted data for the primary outcomes pain, disability and adverse events, and the secondary outcomes of quality of life, emotional well being and participants' ratings of satisfaction or improvement. Only evidence arising from randomised controlled trials was considered. We used the GRADE system to assess the quality of evidence.
We included six Cochrane reviews and 13 non-Cochrane systematic reviews. Cochrane reviews demonstrated better methodological quality than non-Cochrane reviews. Trials were typically small and the quality variable.There is moderate quality evidence that intravenous regional blockade with guanethidine is not effective in CRPS and that the procedure appears to be associated with the risk of significant adverse events.There is low quality evidence that bisphosphonates, calcitonin or a daily course of intravenous ketamine may be effective for pain when compared with placebo; graded motor imagery may be effective for pain and function when compared with usual care; and that mirror therapy may be effective for pain in post-stroke CRPS compared with a 'covered mirror' control. This evidence should be interpreted with caution. There is low quality evidence that local anaesthetic sympathetic blockade is not effective. Low quality evidence suggests that physiotherapy or occupational therapy are associated with small positive effects that are unlikely to be clinically important at one year follow up when compared with a social work passive attention control.For a wide range of other interventions, there is either no evidence or very low quality evidence available from which no conclusions should be drawn.
There is a critical lack of high quality evidence for the effectiveness of most therapies for CRPS. Until further larger trials are undertaken, formulating an evidence-based approach to managing CRPS will remain difficult.
Pain associated with complex regional pain syndrome (CRPS) is frequently excruciating and intractable. The use of botulinum toxin for relief of CRPS-associated pain has not been well described.
To assess whether intramuscular botulinum toxin injections cause relief of pain caused by CRPS, and to assess the risks of this treatment.
Retrospective chart review.
Outpatient clinic.
Patients: 37 patients with spasm/dystonia in the neck and/or upper limb girdle muscles. Intervention: Electromyography-guided injection of botulinum toxin A (BtxA), 10-20 U per muscle. Total dose used was 100 U in each patient. Measurement: Local pain score on an 11 point Likert scale, 4 weeks after BtxA injections.
Mean pain score decreased by 43% (8.2 ± 0.8 to 4.5 ± 1.1, P < 0.001). Ninety-seven percent of the patients had significant pain relief. One patient had transient neck drop after the injections.
This is a retrospective study; it lacks a control group and therefore the placebo effect cannot be eliminated. This study does not provide information on the efficacy of this treatment after 4 weeks.
Intramuscular injection of botulinum toxin A in the upper limb girdle muscles was beneficial for short term relief of pain caused by CRPS in this retrospective case series. The incidence of complications was low (2.7%).
Current IASP diagnostic criteria for CRPS have low specificity, potentially leading to overdiagnosis. This validation study compared current IASP diagnostic criteria for CRPS to proposed new diagnostic criteria (the "Budapest Criteria") regarding diagnostic accuracy. Structured evaluations of CRPS-related signs and symptoms were conducted in 113 CRPS-I and 47 non-CRPS neuropathic pain patients. Discriminating between diagnostic groups based on presence of signs or symptoms meeting IASP criteria showed high diagnostic sensitivity (1.00), but poor specificity (0.41), replicating prior work. In comparison, the Budapest clinical criteria retained the exceptional sensitivity of the IASP criteria (0.99), but greatly improved upon the specificity (0.68). As designed, the Budapest research criteria resulted in the highest specificity (0.79), again replicating prior work. Analyses indicated that inclusion of four distinct CRPS components in the Budapest Criteria contributed to enhanced specificity. Overall, results corroborate the validity of the Budapest Criteria and suggest they improve upon existing IASP diagnostic criteria for CRPS.
Perhaps the most intriguing disorders of body representation are those that are not due to primary disease of brain tissue. Strange and sometimes painful phantom limb sensations can result from loss of afference to the brain; and Complex Regional Pain Syndrome (CRPS)-the subject of the current report-can follow limb trauma without pathology of either the central or peripheral nervous system. This enigmatic and vexing condition follows relatively minor trauma, and can result in enduring misery and a useless limb. It manifests as severe pain, autonomic dysfunction, motor disability and 'neglect-like' symptoms with distorted body representation. For this special issue on body representation we describe the case of a patient suffering from CRPS, including symptoms suggesting a distorted representation of the affected limb. We report contrasting effects of mirror box therapy, as well as a new treatment-prism adaptation therapy-that provided sustained pain relief and reduced disability. The benefits were contingent upon adapting with the affected limb. Other novel observations suggest that: (1) pain may be a consequence, not the cause, of a disturbance of body representation that gives rise to the syndrome; (2) immobilisation, not pain, may precipitate this reorganisation of somatomotor circuits in susceptible individuals; and (3) limitation of voluntary movement is neither due to pain nor to weakness but, rather, to derangement of body representation which renders certain postures from the repertoire of hand movements inaccessible.
Complex regional pain syndrome (CRPS) is a severe chronic pain condition characterized by sensory, autonomic, motor, and dystrophic signs and symptoms. This study was undertaken to expand our current knowledge of the evolution of CRPS signs and symptoms with duration of disease.
This was a retrospective, cross-sectional analysis using data extracted from a patient questionnaire to evaluate the clinical characteristics of CRPS at different time points of disease progression. Data from the questionnaire included pain characteristics and associated symptoms. It also included autonomic, motor, and dystrophic symptoms and also initiating events, ameliorating and aggravating factors, quality of life, work status, comorbid conditions, pattern of pain spread, family history, and demographics. Comparisons were made of different parameters as they varied with disease duration.
A total of 656 patients with CRPS of at least 1-year duration were evaluated. The average age of all participants was 37.5 years, with disease duration varying from 1 to 46 years. The majority of participants were white (96%). A total of 80.3% were females. None of the patients in this study demonstrated spontaneous remission of their symptoms. The pain in these patients was refractory showing only modest improvement with most current therapies.
This study shows that although CRPS is a progressive disease, after 1 year, the majority of the signs and symptoms were well developed and although many variables worsen over the course of the illness, the majority demonstrated only moderate increases with disease duration.
Chronic complex regional pain syndrome (CRPS) is a debilitating pain condition accompanied by autonomic abnormalities. We investigated gray matter morphometry and white matter anisotropy in CRPS patients and matched controls. Patients exhibited a disrupted relationship between white matter anisotropy and whole-brain gray matter volume; gray matter atrophy in a single cluster encompassing right insula, right ventromedial prefrontal cortex (VMPFC), and right nucleus accumbens; and a decrease in fractional anisotropy in the left cingulum-callosal bundle. Reorganization of white matter connectivity in these regions was characterized by branching pattern alterations, as well as increased (VMPFC to insula) and decreased (VMPFC to basal ganglion) connectivity. While regional atrophy differentially related to pain intensity and duration, the strength of connectivity between specific atrophied regions related to anxiety. These abnormalities encompass emotional, autonomic, and pain perception regions, implying that they likely play a critical role in the global clinical picture of CRPS.
Because depression and painful symptoms commonly occur together, we conducted a literature review to determine the prevalence of both conditions and the effects of comorbidity on diagnosis, clinical outcomes, and treatment. The prevalences of pain in depressed cohorts and depression in pain cohorts are higher than when these conditions are individually examined. The presence of pain negatively affects the recognition and treatment of depression. When pain is moderate to severe, impairs function, and/or is refractory to treatment, it is associated with more depressive symptoms and worse depression outcomes (eg, lower quality of life, decreased work function, and increased health care utilization). Similarly, depression in patients with pain is associated with more pain complaints and greater impairment. Depression and pain share biological pathways and neurotransmitters, which has implications for the treatment of both concurrently. A model that incorporates assessment and treatment of depression and pain simultaneously is necessary for improved outcomes.
Local osteopenia and altered bone metabolism are major complications of complex regional pain syndrome (CRPS), but quantitative assessment is difficult unless using X-ray or dual-energy X-ray absorptiometry. Ultrasound-based measurement of bone density (UBD) is a possible alternative, but has never been used to detect unilateral disease such as CRPS. Therefore, the main outcome measure of this prospective study was the diagnostic utility of UBD in patients with lower limb CRPS. Second, we compared the extent of uni- and contralateral calcaneal bone density to that of other conditions with unilateral pain, general osteoporosis, and healthy subjects. Calcaneal osteodensitometry was bilaterally examined using ultrasound-based methodology. Bone mineral density (BMD) values were converted to Z-scores based on age- and sex-dependent reference values. All patients completed a functional and an osteoporosis risk questionnaire. In patients with CRPS (n=18), the BMD values and Z-scores were significantly lower in both the affected (mean ± standard deviation: 0.40±0.08 and -1.1±0.8, respectively) and non-affected (0.46±0.09 and -0.6±0.9, respectively) limbs than in patients (n=40) with other unilateral pain syndromes (affected: 0.51±0.1 and -0.2±1.1, respectively; non-affected: 0.54±0.11 and 0±0.9, respectively) and healthy subjects (right side: 0.6±0.1 and 0.1±0.9, respectively). Conversely, in patients with known systemic osteoporosis, the Z-scores were lower bilaterally with smaller side-to-side differences than in those with CRPS (p<0.05). Compared with subjects suffering from long-term CRPS (≥2.4 years), patients with shorter disease duration exhibited significantly lower Z-scores (p<0.05). In conclusion, UBD revealed that CRPS is associated with both local and systemic alterations of bone metabolism.
Background: To investigate the role of psychological factors (anxiety and depression) and pain measured on a visual analogue scale (VAS) in the development of complex regional pain syndrome type I (CRPS I) following the distal radius fracture (DRF).
Methods: A consecutive sample of patients (N=60) with a distal radius fracture was measured for signs of CRPS by Budapest criteria weekly till 8 weeks and then another follow-up one year after injury to determine the incidence and predictors of developing CRPS I in a prospective cohort study and also to discover whether there is difference between pain, depression, and anxiety level in the patients with and without CRPS I. The most of the patients were treated by Pin stabilization. The Beck depression inventoryshort form (BDI), State-Trait Anxiety Inventory, and Numerical pain rating scale were used to determine the patients’ psychological features and pain intensity at the base line and 8 weeks after the fracture.
Results: CRPS I developed in 15 (25%) patients after eight weeks and just last in 10 (16.67%) patients after one year. No difference was found between the two groups (CRPS and non-CRPS group) in terms of state (STAI-I) and trait (STAI-II) anxiety, and BDI score. Pain at the base line was the most important risk factor in developing CRPS (odds ratio [OR] =1.52; 95% CI).
Conclusions: After fracturing the distal radius, patients who have high pain intensity have a higher risk of developing CRPS I. To following these patients closely for the development of CRPS I may be advantageous for early preventative and therapeutic interventions.
Background:
Remote ischaemic conditioning (RIC) is the cyclic application of non-damaging ischaemia leading to an increased tissue perfusion, among others triggered by NO (monoxide). Complex regional pain syndrome (CRPS) is known to have vascular alterations such as increased blood shunting and decreased NO blood-levels, which in turn lead to decreased tissue perfusion. We therefore hypothesized that RIC could improve tissue perfusion in CRPS.
Method:
In this proof-of-concept study, RIC was applied in the following groups: in 21 patients with early CRPS with a clinical history less than a year, in 20 age/sex-matched controls and in 12 patients with unilateral nerve lesions via a tourniquet on the unaffected/non-dominant upper limb. Blood flow and tissue oxygen saturation (StO2) were assessed before, during and after RIC via laser Doppler and tissue spectroscopy on the affected extremity. The oxygen extraction fraction was calculated.
Results:
After RIC, blood flow declined in CRPS (p < 0.01). StO2decreased in CRPS and healthy controls (p < 0.01). Only in CRPS, the oxygen extraction fraction correlated negatively with the decreasing blood flow (p < 0.05).
Conclusion:
Contrary to our expectations, RIC induced a decrease of blood flow in CRPS, which led to a revised hypothesis: the decrease of blood flow might be due to an anti-inflammatory effect that attenuates vascular disturbances and reduces blood shunting, thus improving oxygen extraction. Further studies could determine whether a repeated application of RIC leads to a reduced hypoxia in chronic CRPS.
Significance:
Remote ischaemic conditioning leads to a decrease of blood flow. This decrease inversely correlates with the oxygen extraction in patients with CRPS.
Background: Complex regional pain syndrome type I is treated symptomatically. A protective effect of vitamin C (ascorbic acid) has been reported previously. A dose-response study was designed to evaluate its effect in patients with wrist fractures.
Methods: In a double-blind, prospective, multicenter trial, 416 patients with 427 wrist fractures were randomly allo- cated to treatment with placebo or treatment with 200, 500, or 1500 mg of vitamin C daily for fifty days. The effect of gender, age, fracture type, and cast-related complaints on the occurrence of complex regional pain syndrome was analyzed.
Results: Three hundred and seventeen patients with 328 fractures were randomized to receive vitamin C, and ninety- nine patients with ninety-nine fractures were randomized to receive a placebo. The prevalence of complex regional pain syndrome was 2.4% (eight of 328) in the vitamin C group and 10.1% (ten of ninety-nine) in the placebo group (p = 0.002); all of the affected patients were elderly women. Analysis of the different doses of vitamin C showed that the prevalence of complex regional pain syndrome was 4.2% (four of ninety-six) in the 200-mg group (relative risk, 0.41; 95% confidence interval, 0.13 to 1.27), 1.8% (two of 114) in the 500-mg group (relative risk, 0.17; 95% confi- dence interval, 0.04 to 0.77), and 1.7% (two of 118) in the 1500-mg group (relative risk, 0.17; 95% confidence inter- val, 0.04 to 0.75). Early cast-related complaints predicted the development of complex regional pain syndrome (relative risk, 5.35; 95% confidence interval, 2.13 to 13.42).
Conclusions: Vitamin C reduces the prevalence of complex regional pain syndrome after wrist fractures. A daily dose of 500 mg for fifty days is recommended.
Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.
This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the effectiveness of physiotherapy interventions for treating pain and disability associated with CRPS types I and II.
Objective . Evaluate the effectiveness of oral steroids in relieving pain in patients with Complex Regional Pain Syndrome (CRPS) of more than 3 months duration.
Design . Service evaluation/Open label uncontrolled trial.
Setting . Two pain outpatient clinics specialized in CRPS diagnosis and treatment in the period 2009–2012.
Subjects . Thirty-one patients diagnosed with CRPS with the Budapest criteria in two specialized centers, with a disease duration of more than 3 months and not responsive to standard treatment were included.
Methods . Patients were treated with oral prednisolone in both centers [100 mg daily tapered by 25 mg every 4 days to zero (Σ1g) at center 1 (C1) and 60 mg daily for 2 weeks lowered 20 mg every 4 days to zero (Σ1.06g) at center 2 (C2)]. The average pain intensity was recorded by patients using a numeric rating scale before the treatment start, and 6 weeks after treatment onset (treatment duration was respectively 16 days and 22 days at the two centers).
Results . Overall the authors observed no significant reduction in the average pain intensity ( P = 0.059), but 2 patients had a consistent reduction in pain intensity with return to baseline pain levels 9 weeks after treatment onset, and 1 patient had ongoing stable pain relief of >50%.
Conclusions . This study provides indications that the efficacy of oral corticosteroids is limited in treating CRPS of more than 3 months duration who did not respond to previous treatment. Randomized controlled studies (with enriched designs), or single subject designs would be required to identify the possible existence of a patient subgroup with a specific disease profile that may benefit from a steroid treatment.
Background:
Treatment of long-standing complex regional pain syndrome (CRPS) is empirical and often of limited efficacy. Preliminary data suggest that the immune system is involved in sustaining this condition and that treatment with low-dose intravenous immunoglobulin (IVIG) may substantially reduce pain in some patients.
Objective:
To evaluate the efficacy of IVIG in patients with longstanding CRPS under randomized, controlled conditions.
Design:
A randomized, double-blind, placebo-controlled crossover trial. (National Research Registry number: N0263177713; International Standard Randomised Controlled Trial Number Registry: 63918259)
Setting:
University College London Hospitals Pain Management Centre.
Patients:
Persons who had pain intensity greater than 4 on an 11-point (0 to 10) numerical rating scale and had CRPS for 6 to 30 months that was refractory to standard treatment.
Intervention:
IVIG, 0.5 g/kg, and normal saline in separate treatments, divided by a washout period of at least 28 days.
Measurements:
The primary outcome was pain intensity 6 to 19 days after the initial treatment and the crossover treatment.
Results:
13 eligible participants were randomly assigned between November 2005 and May 2008; 12 completed the trial. The average pain intensity was 1.55 units lower after IVIG treatment than after saline (95% CI, 1.29 to 1.82; P < 0.001). In 3 patients, pain intensity after IVIG was less than after saline by 50% or more. No serious adverse reactions were reported.
Limitation:
The trial was small, and recruitment bias and chance variation could have influenced results and their interpretation.
Conclusion:
IVIG, 0.5 g/kg, can reduce pain in refractory CRPS. Studies are required to determine the best immunoglobulin dose, the duration of effect, and when repeated treatments are needed.
Primary funding source:
Association of Anaesthetists of Great Britain and Ireland, University College London Hospitals Charity, and CSL-Behring.
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Although the cause of reflex sympathetic dystrophy (RSD) remains unknown, hyperactivity of the sympathetic nerves and secondary vasospasm may be pathogenic in this syndrome. A retrospective epidemiologic study of RSD was done on 53 in-patients from 1978–1985. Cigarette smoking was strikingly increased in patient frequency in RSD (68% versus 37% of hospitalized controls, p < 0.0001). Eighty-seven percent of the patients had a history of trauma or surgery, and 38% had other associated diseases. Cigarette smoking is statistically linked to RSD and may be involved in its pathogenesis by enhancing sympathetic activity, vasoconstriction, or by some other unknown mechanism.
Neurologist S. Weir Mitchell first described “causalgia” following wartime nerve injury, with its persistent distal limb burning pain, swelling, and abnormal skin color, temperature, and sweating. Similar post-traumatic symptoms were later identified in patients without overt nerve injuries after trauma. This was labeled reflex sympathetic dystrophy (RSD; now complex regional pain syndrome type I [CRPS-I]). The pathophysiology of symptoms is unknown and treatment options are limited. We propose that persistent RSD/CRPS-I is a post-traumatic neuralgia associated with distal degeneration of small-diameter peripheral axons. Small-fiber lesions are easily missed on examination and are undetected by standard electrophysiological testing. Most CRPS features—spreading pain and skin hypersensitivity, vasomotor instability, osteopenia, edema, and abnormal sweating—are explicable by small-fiber dysfunction. Small fibers sense pain and temperature but also regulate tissue function through neuroeffector actions. Indeed, small-fiber–predominant polyneuropathies cause CRPS-like abnormalities, and pathological studies of nerves from chronic CRPS-I patients confirm small-fiber–predominant pathology. Small distal nerve injuries in rodents reproduce many CRPS features, further supporting this hypothesis. CRPS symptoms likely reflect combined effects of axonal degeneration and plasticity, inappropriate firing and neurosecretion by residual axons, and denervation supersensitivity. The resulting tissue edema, hypoxia, and secondary central nervous system changes can exacerbate symptoms and perpetuate pathology. Restoring the interest of neurologists in RSD/CRPS should improve patient care and broaden our knowledge of small-fiber functions. Ann Neurol 2009;65:629–638
Patients with complex regional pain syndrome (CRPS) and intractable pain showed a shrinkage of cortical maps on primary (SI) and secondary somatosensory cortex (SII) contralateral to the affected limb. This was paralleled by an impairment of the two-point discrimination thresholds. Behavioral treatment over 1 to 6 months consisting of graded sensorimotor retuning led to a persistent decrease in pain intensity, which was accompanied by a restoration of the impaired tactile discrimination and regaining of cortical map size in contralateral SI and SII. This suggests that the reversal of tactile impairment and cortical reorganization in CRPS is associated with a decrease in pain. Ann Neurol 2005;57:425–429
Amputation for the treatment of long-standing, therapy-resistant complex regional pain syndrome type I (CRPS-I) is controversial. An evidence-based decision regarding whether or not to amputate is not possible on the basis of current guidelines. The aim of the current study was to systematically review the literature and summarize the beneficial and adverse effects of an amputation for the treatment of long-standing, therapy-resistant CRPS-I.
A literature search, using MeSH terms and free text words, was performed with use of PubMed and EMBASE. Original studies published prior to January 2010 describing CRPS-I as a reason for amputation were included. The reference lists of the identified studies were also searched for additional relevant studies. Studies were assessed with regard to the criteria used to diagnose CRPS-I, level of amputation, amputation technique, rationale for the level of amputation, reason for amputation, recurrence of CRPS-I after the amputation, phantom pain, prosthesis fitting and use, and patient functional ability, satisfaction, and quality of life.
One hundred and sixty articles were identified, and twenty-six studies with Level-IV evidence (involving 111 amputations in 107 patients) were included. Four studies applied CRPS-I diagnostic criteria proposed by the International Association for the Study of Pain, Bruehl et al., or Veldman et al. Thirteen studies described symptoms without noting whether the patient met diagnostic criteria for CRPS-I, and nine studies stated the diagnosis only. The primary reasons cited for amputation were pain (80%) and a dysfunctional limb (72%). Recurrence of CRPS-I in the stump occurred in thirty-one of sixty-five patients, and phantom pain occurred in fifteen patients. Thirty-six of forty-nine patients were fitted with a prosthesis, and fourteen of these patients used the prosthesis. Thirteen of forty-three patients had paid employment after the amputation. Patient satisfaction was reported in eight studies, but the nature of the satisfaction was often not clearly indicated. Changes in patient quality of life were reported in three studies (fifteen patients); quality of life improved in five patients and the joy of life improved in another six patients.
The previously published studies regarding CRPS-I as a reason for amputation all represent Level-IV evidence, and they do not clearly delineate the beneficial and adverse affects of an amputation performed for this diagnosis. Whether to amputate or not in order to treat long-standing, therapy-resistant CRPS-I remains an unanswered question.
Complex regional pain syndrome (CRPS) usually develops after trauma. We are reporting the first case of CRPS with leprosy as a precipitating cause. A fifty-five-year male presented in the pain clinic with complaint of pain and swelling in the right arm. There was no history of trauma to the limb. On reviewing the history, patient was found to be on treatment for leprosy. X-ray of the right hand showed severe osteoporosis. A diagnosis of CRPS associated with leprosy was made. A diagnostic stellate ganglion block relived his pain completely. Thereafter patient is on treatment with tablet etoricoxib 90 mg once a day, gabapentin 100 mg twice a day and continuing to have 100% pain relief. The diagnosis of the type of CRPS was difficult in our case as no history of trauma or neurological injury was present. The presence of leprosy along with ulnar nerve thickening may be the precipitating factor for CRPS, this has not been reported so far in the literature. We managed the patient with sympathetic block along with medical therapy for chronic pain and leprosy chemotherapy.
Neurologist S. Weir Mitchell first described "causalgia" following wartime nerve injury, with its persistent distal limb burning pain, swelling, and abnormal skin color, temperature, and sweating. Similar post-traumatic symptoms were later identified in patients without overt nerve injuries after trauma. This was labeled reflex sympathetic dystrophy (RSD; now complex regional pain syndrome type I (CRPS-I)). The pathophysiology of symptoms is unknown and treatment options are limited. We propose that persistent RSD/CRPS-I is a post-traumatic neuralgia associated with distal degeneration of small-diameter peripheral axons. Small-fiber lesions are easily missed on examination and are undetected by standard electrophysiological testing. Most CRPS features—spreading pain and skin hypersensitivity, vasomotor instability, osteopenia, edema, and abnormal sweating—are ex- plicable by small-fiber dysfunction. Small fibers sense pain and temperature but also regulate tissue function through neuroef- fector actions. Indeed, small-fiber-predominant polyneuropathies cause CRPS-like abnormalities, and pathological studies of nerves from chronic CRPS-I patients confirm small-fiber-predominant pathology. Small distal nerve injuries in rodents repro- duce many CRPS features, further supporting this hypothesis. CRPS symptoms likely reflect combined effects of axonal degen- eration and plasticity, inappropriate firing and neurosecretion by residual axons, and denervation supersensitivity. The resulting tissue edema, hypoxia, and secondary central nervous system changes can exacerbate symptoms and perpetuate pathology. Re- storing the interest of neurologists in RSD/CRPS should improve patient care and broaden our knowledge of small-fiber func- tions. Ann Neurol 2009;65:629 - 638
Joint and bone alterations are seldom mentioned in the diagnostic criteria for complex regional pain syndrome (CRPS) even though they are important for long-term outcome. Altered periarticular bone metabolism can be detected by 3-phase bone scintigraphy (TPBS). Although frequently examining the diagnostic efficacy of TPBS is debatable.
In all, 78 TPBS (45 CRPS/33 control group) were evaluated qualitatively and quantitatively. Sensitivity and specificity of the qualitative blinded reviewer analysis (n=57) compared with quantitative region of interest (ROI)-based analysis over the metacarpophalangeal, proximal, and distal interphalangeal joints (n=74) were evaluated. Patients' sex, age, duration of CRPS, inciting event, extent of joint alteration, and handedness were included as covariables.
Qualitative blinded reviewer TPBS analysis had a high specificity (83%-100%). However, sensitivity was 31% to 50%. Interrater reliability was moderate (kappa score 0.56). Using the ROI-based evaluation, the highest sensitivity (69%) and specificity (75%) (ROI score > or =1.32) was shown for phase 3, whereas sensitivity of phases 1 and 2 rapidly declined to 50%. Duration of CRPS until TPBS was the only variable with significant impact on ROI scores of phase 3 (F=23.7; P=0.000; R=0.42). ROI scores declined with increasing duration of CRPS.
In conclusion, TPBS is a highly specific tool for diagnosing CRPS of the upper limb. ROI evaluation of phase 3 within the first 5 months after onset of CRPS is an appropriate additional diagnostic tool to confirm or exclude CRPS of the upper extremity.
Treatment of long-standing complex regional pain syndrome (CRPS) is empirical and often of limited efficacy. Preliminary data suggest that the immune system is involved in sustaining this condition and that treatment with low-dose intravenous immunoglobulin (IVIG) may substantially reduce pain in some patients.
To evaluate the efficacy of IVIG in patients with longstanding CRPS under randomized, controlled conditions.
A randomized, double-blind, placebo-controlled crossover trial. (National Research Registry number: N0263177713; International Standard Randomised Controlled Trial Number Registry: 63918259)
University College London Hospitals Pain Management Centre.
Persons who had pain intensity greater than 4 on an 11-point (0 to 10) numerical rating scale and had CRPS for 6 to 30 months that was refractory to standard treatment.
IVIG, 0.5 g/kg, and normal saline in separate treatments, divided by a washout period of at least 28 days.
The primary outcome was pain intensity 6 to 19 days after the initial treatment and the crossover treatment.
13 eligible participants were randomly assigned between November 2005 and May 2008; 12 completed the trial. The average pain intensity was 1.55 units lower after IVIG treatment than after saline (95% CI, 1.29 to 1.82; P < 0.001). In 3 patients, pain intensity after IVIG was less than after saline by 50% or more. No serious adverse reactions were reported.
The trial was small, and recruitment bias and chance variation could have influenced results and their interpretation.
IVIG, 0.5 g/kg, can reduce pain in refractory CRPS. Studies are required to determine the best immunoglobulin dose, the duration of effect, and when repeated treatments are needed.
Association of Anaesthetists of Great Britain and Ireland, University College London Hospitals Charity, and CSL-Behring.
Complex regional pain syndrome type I (CRPS I) is a neuropathic pain disorder of unclear etiology. It commonly follows a trivial injury and is characterized by spontaneous pain manifesting regionally that is disproportionate to the inciting event. Associated signs and symptoms include allodynia, hyperalgesia, edema, sudomotor, vasomotor abnormalities, and trophic changes. Although multiple modalities exist to treat CRPS I, significant disability, diminution in quality of life, and reduction in overall health often accompany the syndrome.
A case of a 57-year-old man with CRPS I who was treated with spinal cord stimulation (SCS) after failing conservative therapy is presented. One month following treatment, he experienced complete symptom resolution such that stimulation was subsequently discontinued without recurrence over the 1-year follow-up period.
To date there is currently no reliably validated "cure" for CRPS. There has only been one recent report where SCS resulted in the complete eradication of the signs and symptoms associated with CRPS. This series involved adolescent girls aged 11-14 years of age, who tend to have a more benign and self-limited treatment course than that seen in adults. This raises the question as to whether a "neural switch" exists, and if so, where it is located. We postulate that the inter-neuronal connections between the central and peripheral nervous systems implicated by the current pathophysiological model is the most plausible site of this "neural switch," and that reorganization of this interface can account for the ability of SCS to effect a complete "cure" in CRPS.
Antihypertensive drugs interact with mediators that are also involved in complex regional pain syndrome (CRPS), such a neuropeptides, adrenergic receptors, and vascular tone modulators. Therefore, we aimed to study the association between the use of antihypertensive drugs and CRPS onset. We conducted a population-based case-control study in the Integrated Primary Care Information (IPCI) database in the Netherlands. Cases were identified from electronic records (1996-2005) and included if they were confirmed during an expert visit (using IASP criteria), or if they had been diagnosed by a medical specialist. Up to four controls per cases were selected, matched on gender, age, calendar time, and injury. Exposure to angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, beta-blockers, calcium channel blockers, and diuretics was assessed from the automated prescription records. Data were analyzed using multivariate conditional logistic regression. A total of 186 cases were matched to 697 controls (102 confirmed during an expert visit plus 84 with a specialist diagnosis). Current use of ACE inhibitors was associated with an increased risk of CRPS (OR(adjusted): 2.7, 95% CI: 1.1-6.8). The association was stronger if ACE inhibitors were used for a longer time period (OR(adjusted): 3.0, 95% CI: 1.1-8.1) and in higher dosages (OR(adjusted): 4.3, 95% CI: 1.4-13.7). None of the other antihypertensive drug classes was significantly associated with CRPS. We conclude that ACE inhibitor use is associated with CRPS onset and hypothesize that ACE inhibitors influence the neuro-inflammatory mechanisms that underlie CRPS by their interaction with the catabolism of substance P and bradykinin.
Knowledge concerning the medical history prior to the onset of complex regional pain syndrome (CRPS) might provide insight into its risk factors and potential underlying disease mechanisms. To evaluate prior to CRPS medical conditions, a case-control study was conducted in the Integrated Primary Care Information (IPCI) project, a general practice (GP) database in the Netherlands. CRPS patients were identified from the records and validated through examination by the investigator (IASP criteria) or through specialist confirmation. Cases were matched to controls on age, gender and injury type. All diagnoses prior to the index date were assessed by manual review of the medical records. Some pre-specified medical conditions were studied for their association with CRPS, whereas all other diagnoses, grouped by pathogenesis, were tested in a hypothesis-generating approach. Of the identified 259 CRPS patients, 186 cases (697 controls) were included, based on validation by the investigator during a visit (102 of 134 visited patients) or on specialist confirmation (84 of 125 unvisited patients). A medical history of migraine (OR: 2.43, 95% CI: 1.18-5.02) and osteoporosis (OR: 2.44, 95% CI: 1.17-5.14) was associated with CRPS. In a recent history (1-year before CRPS), cases had more menstrual cycle-related problems (OR: 2.60, 95% CI: 1.16-5.83) and neuropathies (OR: 5.7; 95% CI: 1.8-18.7). In a sensitivity analysis, including only visited cases, asthma (OR: 3.0; 95% CI: 1.3-6.9) and CRPS were related. Psychological factors were not associated with CRPS onset. Because of the hypothesis-generating character of this study, the findings should be confirmed by other studies.
The X-rays of 17 patients with fresh fractures of the lunate bone have been reviewed. The fractures were classified according to their radiological appearances and according to the vascular anatomy of the lunate. A long term X-ray follow-up examination was performed.
Although the cause of reflex sympathetic dystrophy (RSD) remains unknown, hyperactivity of the sympathetic nerves and secondary vasospasm may be pathogenic in this syndrome. A retrospective epidemiologic study of RSD was done on 53 in-patients from 1978-1985. Cigarette smoking was strikingly increased in patient frequency in RSD (68% versus 37% of hospitalized controls, p less than 0.0001). Eighty-seven percent of the patients had a history of trauma or surgery, and 38% had other associated diseases. Cigarette smoking is statistically linked to RSD and may be involved in its pathogenesis by enhancing sympathetic activity, vasoconstriction, or by some other unknown mechanism.
The pathogenesis of reflex sympathetic dystrophy--variously known as Sudeck's atrophy, causalgia, algodystrophy, and peripheral trophoneurosis--is not yet understood, and diagnosing and treating patients is difficult. We have prospectively studied 829 patients, paying particular attention to early signs and symptoms. In its early phase, reflex sympathetic dystrophy is characterised by regional inflammation, which increases after muscular exercise. Pain was present in 93% of patients, and hypoaesthesia and hyperpathy were present in 69% and 75% respectively. With time, tissue atrophy may occur as well as involuntary movements, muscle spasms, or pseudoparalysis. Tremor was found in 49% and muscular incoordination in 54% of patients. Sympathetic signs such as hyperhidrosis are infrequent and therefore have no diagnostic value. We found no evidence consistent with the presence of three consecutive phases of the disease. Early symptoms are those of an inflammatory reaction and not of a disturbance of the sympathetic nervous system. These data support the concept of an exaggerated regional inflammatory response to injury or operation in reflex sympathetic dystrophy.
We made a prospective study of the incidence and natural history of algodystrophy and associated changes in bone mineral density in the ankles and feet of 60 consecutive patients who had suffered unilateral fractures of the tibial shaft. At bone union, 18 patients showed signs of algodystrophy. Its development was independent of the type of fracture management and of the severity of injury. Patients with algodystrophy lost significantly more bone mineral than did those without but the degree of this loss was independent of the type of treatment and of the time to fracture union. In most cases the symptoms resolved within six months of fracture union but in four patients they were still present at one year and two of these had not returned to work.
To assess the sensitivity, specificity, and predictive value (PV) of stress infrared telethermography (IRT) in the complex regional pain syndrome, type I (CRPS-I).
One hundred eighty-five consecutive patients (47 men, 138 women) with 205 pairs of chronically painful limbs (upper, lower, or both) were examined by pain specialists in neurology, physiatry, and anesthesia, who then reached a consensus diagnosis. A clinical diagnosis of CRPS-I required at least two of the following observations: burning pain, vasomotor changes, diaphoresis, trophic changes, allodynia. Patients with only one criterion were classified as possible CRPS-I; those with none were judged not to have CRPS-I. Patients and 24 asymptomatic control subjects underwent stress IRT, which was considered positive for CRPS-I if it showed three of the following: quantitative thermal emission of > or = 1.00 degree C, abnormal distal thermal gradient patterns, presence of a "thermal marker," and abnormal response to functional cold water autonomic stress testing.
By clinical criteria, CRPS-I was diagnosed in 73 pairs of limbs; not CRPS-I was diagnosed in 70; and 62 pairs had possible CRPS-I. Excluding possible CRPS-I cases, there were 5 false-negative stress IRTs (sensitivity 93%) and 7 false-positive results (specificity 89%). Based on estimated 50% prior probability for our population, the positive PV is 90% and the negative PV 94%. None of the control subjects exhibited thermographic evidence of CRPS-I.
Stress IRT is a sensitive and specific indicator of CRPS-I.
Stellate ganglion (SG) blockade is used for the treatment of chronic pain syndromes in which the sympathetic nervous system is hypothesized to be involved. A possible treatment modality to achieve long-term pain reduction is blockade of the SG by means of a radiofrequency lesion (RF-SG). To evaluate the outcome of RF-SG as a therapy for different chronic pain syndromes, we reviewed 86 RF-SG procedures.
Medical records containing treatment information were reviewed systematically. A systematic MEDLINE literature review search on SG blockade was also performed.
In our clinic, 39.5% of 221 patients who received a prognostic SG block subsequently underwent RF-SG. Of these patients, 40.7% noted a more than 50% reduction of pain, 54.7% reported no effect on pain, and 4.7% showed worsening of pain. The mean follow-up interval was 52 weeks. The computer-assisted literature search resulted in 31 studies: 12 about complications and 19 about the efficacy of SG blockade. A review of these studies showed partial pain relief in 41.3% of patients, complete pain relief in 37.8%, and no pain relief in 20.9%.
The efficacy of RF-SG blockade seems to be in line with that of other SG blockade procedures reported in the literature. Our retrospective study shows that an RF-SG block is most likely to be of benefit for patients suffering from complex regional pain syndrome type 2, ischemic pain, cervicobrachialgia, or postthoracotomy pain. Clinical efficacy remains to be proven in a randomized controlled trial, however.
Complex regional pain syndrome type I (CRPS I) is a chronic painful disease of one extremity that may develop as a disproportionate consequence of a trauma affecting the limbs without overt nerve injury. It is clinically characterized by sensory, motor and autonomic symptoms including vascular abnormalities. Previously, we have reported that pathophysiological alterations of the ongoing sympathetic activity play a crucial role in vasomotor disturbances (Brain 124 (2001) 587). As a companion article, the aim of this study was to evaluate the diagnostic value of skin temperature side differences in consideration of the spontaneous sympathetic vasoconstrictor activity. Twenty-five patients with CRPS I were studied. Fifteen patients with painful limbs of other origin and 20 healthy individuals served as controls. Controlled thermoregulation was performed to change cutaneous sympathetic vasoconstrictor activity by the use of a thermal suit: skin sympathetic vasoconstrictor neurones were activated by whole-body cooling and nerve activity was abolished by whole-body warming. Skin temperature at the affected and unaffected limbs (infra-red thermometry) was measured under resting conditions and continuously monitored during controlled modulation of sympathetic activity. The results showed only minor skin temperature asymmetries between both limbs under resting conditions in most CRPS patients. However, during controlled thermoregulation temperature differences between both sides increased dynamically and were most prominent at a high to medium level of vasoconstrictor activity. In both control groups, there were only minor side differences in temperature both in rest and during thermoregulatory changes of sympathetic activity. When comparing the diagnostic value of skin temperature asymmetries in CRPS I, sensitivity was only 32% under resting conditions, but increased up to 76% during controlled alteration of sympathetic activity. Specificity was 100% at rest and 93% at controlled thermoregulation. We concluded that the degree of unilateral vascular disturbances in CRPS I depends critically on spontaneous sympathetic activity. Taking this into consideration, skin temperature differences in the distal limbs are capable of reliably distinguishing CRPS I from other extremity pain syndromes with high sensitivity and specificity.