Mechanisms of complex regional pain syndrome

Background: Complex regional pain syndrome type I (CRPS I), also known as reflex sympathetic dystrophy (RSD), develops as disabling painful disorder following a trauma or surgery to a limb. We provide a review based on the current literature concerning the epidemiology and pathophysiology of CRPS I. Possible pathophysiological mechanisms of CRPS I are inflammation, sympathetic-afferent coupling and cortical changes. Methods: A literature search was conducted using, as electronic bibliographic database, Medline from 1980 until today. Results: CRPS I is a multifactorial disorder with complex aetiology and pathogenesis. Conclusions: The pathophysiology of CRPS I is complex and may change during its course. CRPS I is more than a peripheral disease because peripheral mechanisms such as neurogenic inflammation and sympathetic-afferent coupling inconclusively explain its pathophysiology. CRPS I is a pain disorder involving the somatosensory, the somatomotor and the sympathetic nervous systems. Genetic findings suggest there might be a predisposition to CRPS I and it has been confirmed in multiple studies that psychological factors are not predictors for the development of CRPS I. The complexity and diversity of the mechanisms involved will be liable to the heterogeneity of the clinical presentation and may explain the difficulty of achieving an evidence-based treatment of CRPS I. Keywords: Complex Regional Pain Syndrome; Reflex Sympathetic Dystrophy; Neurogenic Inflammation; Sympathetic Nervous System; Neuropathic Pain.

Pain Research and Management

The purpose of this review is to summarize the pathophysiology of complex regional pain syndrome (CRPS), the underlying molecular mechanisms, and potential treatment options for its management. CRPS is a multifactorial pain condition. CRPS is characterized by prolonged or excessive pain and changes in skin color and temperature, and/or swelling in the affected area, and is generally caused by stimuli that lead to tissue damage. An inflammatory response involving various cytokines and autoantibodies is generated in response to acute trauma/stress. Chronic phase pathophysiology is more complex, involving the central and peripheral nervous systems. Various genetic factors involved in the chronicity of pain have been identified in CRPS patients. As with other diseases of complex pathology, CRPS is difficult to treat and no single treatment regimen is the same for two patients. Stimulation of the vagus nerve is a promising technique being tested for different gastrointestinal and inflamm...

Medical Hypotheses

Complex Regional Pain Syndrome (CRPS) has defied a clear unified pathological explanation to date. Not surprisingly, treatments for the condition are limited in number, efficacy and their ability to enact a cure. Whilst many observations have been made of physiological abnormalities, how these explain the condition and who does and doesn't develop CRPS remains unclear. We propose a new overarching hypothesis to explain the condition that invokes four dynamically changing and interacting components of tissue trauma, pathological pain processing, autonomic dysfunction (both peripheral and central) and immune dysfunction, primarily involving excessive and pathological activation of dendritic cells following trauma or atrophy. We outline pathophysiological changes that may initiate a cascade of events involving dendritic cells and the cholinergic antiinflammatory pathway resulting in the condition, and the changes that maintain the condition into its chronic phase. This hypothesis should provide fertile ground for further investigations and development of new treatments that holistically address the nature of the disorder along its developmental continuum.

Clinical and Experimental Pharmacology and Physiology, 2008

1. In diseases such as complex regional pain syndrome (CRPS), where neuropathic pain is the primary concern, traditional pain classifications and lesion descriptors are of limited value. To obtain better treatment outcomes for patients, the underlying pathophysiological mechanisms of neuropathic pain need to be elucidated and analysed so that therapeutic targets can be identified and specific treatments developed.

Current Opinion in Anesthesiology, 2014

Purpose of review The incidence and disease course of complex regional pain syndrome (CRPS) has been unclear until recently. This was due to inconsistent diagnostic criteria used in previous studies and a lack of large-scale prospective datasets. Multiple mechanisms of CRPS have been suggested, and recent research has begun to explain how inflammation, the immune system and the autonomic nervous system may interact with aberrant central neuroplasticity to produce the clinical picture. This review summarizes progress in these fields. Recent findings National registries of patients with CRPS have provided us with an invaluable insight into the epidemiology of the disorder. We now have a better understanding of the disease course and expected outcome. Widespread sensory abnormalities, not limited to the CRPS limb, have been found suggesting that systemic changes may occur. Parietal lobe dysfunction and problems with sensory-motor integration have also been revealed. Abnormalities in the immune system in CRPS have also been demonstrated. Summary Recent findings in diverse research fields suggest novel treatment options for CRPS: from targeting autoimmunity to correcting abnormal body image. Many of the advances in our understanding of CRPS have arisen from the development of collaborative research efforts, such as the TREND group in the Netherlands.

PLoS ONE, 2008

Background: Sensory abnormalities are a key feature of Complex Regional Pain Syndrome (CRPS). In order to characterise these changes in patients suffering from acute or chronic CRPS I, we used Quantitative Sensory Testing (QST) in comparison to an age and gender matched control group.

La Tunisie médicale, 2012

If the pathophysiology of complex regional pain syndrome (CRPS) type 1 remains controversial, most authors agree on a combination in varying proportions, a sensitization of peripheral nerves. To describe the state of advances in the physiopathology of complex regional pain syndrome type 1. Bibliographic research and literature review performed by referring to databases (Medline, Science Direct) The physiopathology of complex regional pain syndrome type 1 remains still poorly understood and controversial. Several arguments demonstrated both peripheral (inflammation, abnormal sympathetic ...) and central (neurological and cognitive) mechanisms. A better knowledge of the physiopathology of complex pain syndrome type 1 is necessary in order to adapt efficient curative therapy or to a better prevention of this syndrome.

Autoimmunity reviews, 2014

Complex regional pain syndrome (CRPS) is a term used to describe a variety of disorders characterized by spontaneous or stimulus-induced pain that is disproportional to the inciting event and accompanied by a myriad of autonomic and motor disturbances in highly variable combinations. There are no standards which can be applied to the diagnosis and would fulfill definitions of evidence-based medicine. Indeed, there are almost as many diagnostic criteria as there are names to this disorder. The umbrella term CRPS has been subdivided into type I and type II. CRPS I is intended to encompass reflex sympathetic dystrophy and similar disorders without a nerve injury; while CRPS II occurs after damage to a peripheral nerve. There are numerous etiological pathophysiological events that have been incriminated in development of CRPS, including inflammation, autoimmune responses, abnormal cytokine production, sympathetic-sensory disorders, altered blood flow and central cortical reorganization....

Journal of Bodywork and Movement Therapies, 2004

Physical therapists and other health care providers frequently evaluate and treat patients with complex regional pain syndrome (CRPS). The term CRPS replaces the previous terms reflex sympathetic dystrophy (now referred to as CRPS Type I) and causalgia (CRPS Type II). Part 1 of this paper describes the diagnostic criteria for CRPS and the clinical features and etiology of both CRPS Types I and II. CRPS is a multifactorial syndrome with overlapping symptoms. Although much progress has been made in the understanding of CRPS, many questions remain unanswered. CRPS is probably a disease of the central nervous system. Yet, peripheral inflammatory processes, abnormal sympathetic-afferent coupling, and adrenoreceptor pathology may also be part of the picture. It is likely that in the near future the current concepts of CRPS will be replaced by a new mechanism-based term or group of terms leading to improved clinical guidelines. Part 2 in this series reviews the physical therapy management of patients with CRPS.

2013