Despite clinical similarities there are significant differences between acute limb trauma and complex regional pain syndrome I (CRPS I).

In order to analyze the pathophysiology behind the clinical similarity acutely after limb trauma and in acute stages of complex regional pain syndrome (CRPS), 20 patients with external fixation after distal radius fracture (3.5 days after surgery) without signs of CRPS and 24 patients suffering from acute CRPS I (without nerve lesion; duration, 5 weeks) were investigated. Hyperalgesia to heat was tested by a feedback-controlled thermode, and to mechanical stimuli by an impact stimulator. The sympathetic nervous system was examined by measuring skin temperature (infra-red thermography), testing different sympathetic vasoconstrictor reflexes (laser-Doppler flowmetry) and quantitative sudometry after thermal load (thermoregulatory sweat test). We found hyperalgesia to heat after trauma (P<0.001), but not in CRPS, whereas mechanical hyperalgesia was present in both patient groups (trauma: P<0.001; CRPS: P<0.005). Skin temperature was significantly increased on the affected side in both patient groups (acute trauma: P<0.001; CRPS: P<0.005). However, sympathetic failure, as indicated by impairment of sympathetic vasoconstrictor reflexes (P<0.02) and hyperhidrosis (P<0.01), was found exclusively in CRPS patients. Our results indicate that pain and vasomotor disturbances may be generated by different mechanisms acutely after trauma and in acute CRPS. Despite the clinical similarity, additional changes in the peripheral or central nervous system are required for CRPS. In the light of our observations, it seems unlikely that CRPS is a simple exaggeration of post-traumatic inflammation.     

Can complex regional pain syndrome be painless?

While spontaneous and stimulus-evoked pain are the hallmarks of complex regional pain syndrome (CRPS), also known as reflex sympathetic dystrophy, autonomic abnormalities, motor dysfunction, and trophic changes in the affected limb are additional clinical characteristics distinguishing this syndrome. Even though the exact underlying mechanisms of the syndrome remain obscure, a recent hypothesis suggests that the abnormal response of neural nociceptive tissue plays a major role in the pathogenesis of CRPS via the mechanism known as 'neurogenic inflammation'.The group of patients presented here exhibited all the clinical characteristics of CRPS but had no pain, thereby indicating that ongoing or evoked pain is not a necessary condition for CRPS to be maintained. We suggest the term complex regional painless syndrome to describe this syndrome.     

Interventional therapies in the management of complex regional pain syndrome

Invasive procedures have long held a place in the therapeutic armamentarium for the management of complex regional pain syndrome (CRPS). However, this has evolved considerably, particularly as research into the mechanisms of CRPS has called into question long-held presumptions about the key role of sympathetic dysfunction in the syndrome. This review summarizes some of the key information currently available about interventional treatments, including nerve blocks, spinal cord and peripheral nerve stimulation, chemical and surgical sympathectomies, and deep brain stimulation. The potential roles for these procedures in facilitating functional rehabilitation goals that are primary to the treatment of CRPS are emphasized.     

Complex regional pain syndrome and chiropractic

OBJECTIVE: Complex regional pain syndromes (CRPS) represent curious and difficult syndromes for both patient and clinician. CRPS presents as a triad of signs and symptoms, usually after a seemingly trivial injury to a peripheral joint or appendage. The clinical triad includes severe pain, vasomotor changes in and around the affected area, and trophic changes in the affected limb. Many of the acute symptoms are similar to those seen after many acute injuries, which makes an early diagnosis often times difficult. Current treatment protocols revolve around aggressive physical therapy plus pharmacologic interventions aimed at limiting sympathetic nervous system activity. OBJECTIVE: To review the literature on CRPS regarding symptoms, diagnosis, treatment, and causal mechanisms and to discuss alternative treatment approaches and the possible role of chiropractic care in patient rehabilitation. Data Sources: Texts, review articles, and randomized clinical trials investigating treatments, causes, and epidemiology. CONCLUSIONS: Recent research calls into question the predominant theories that view excessive sympathetic nervous system activity as the cause of CRPS. No evidence of an increase in sympathetic nervous system activity has been found, and new theories suggest that an increase in the sensitivity of neurotransmitter receptors may be the cause of CRPS. Alternatively, other research has suggested that a local inflammatory process may in fact cause CRPS. Although no research has been completed examining the role of chiropractic care in the treatment of CRPS, there is reason to believe that spinal manipulation may be beneficial to patients with CRPS.     

Clinical Science (37)

Pain relief in complex regional pain syndrome due to spinal cord stimulation does not depend on vasodilation. (Maastricht University Hospital, Maastricht, The Netherlands) Anesthesiology 2000;92:1653–1660. This study aimed to assess whether pain relief in complex regional pain syndrome (CRPS after spinal cord stimulation (SCS) is, in fact, dependent on vasodilation. In addition, the study attempted to determine which of the potential mechanisms may cause the vasodilatory effect that is generally found after SCS. Twenty‐four of 36 patients with unilateral CRPS responded to the test of SCS. Twenty‐two of the 24 responders (hand, n = 14; foot, n = 8) who had undergone previous sympathectomy were enrolled in the study. In addition, 20 control subjects (10 controls for each extremity) were studied. By means of laser Doppler flowmetry, the skin microcirculation of the patients was measured bilaterally while the SCS system was switched off and while it was activated. Control subjects were tested only once. The ratio of the rest flow at heart level and the dependent position was defined as the vasoconstricted index. Both in affected hands and feet, patients were found to have lower vasoconstriction indices (P < 0.01) as compared with controls, indicating a decreased sympathetic tone. Applying SCS did not result in any microcirculatory change as compared with the baseline or the contralateral clinically unaffected side. Conclude that the study failed to show that SCS influences skin microcirculation in patients with CRPS and a low sympathetic tone. Therefore, it was also concluded that pain relief in CRPS due to SCS is possible without vasodilation. Because sympathetic activity was greatly decreased in the patients, these results support the hypothesis that the vasodilation that is normally found with SCS is due to an inhibitory effect on sympathetically maintained vasoconstriction. Comment by Hemmo A. Bosscher, MD. SCS probably provides pain relief independent of increases in blood flow to the affected area. There may be several weaknesses in this study. All patients underwent prior sympathectomy. As every pain management specialist knows, the results of these procedures are variable. That leaves a group of pain patients with CRPS I that is either predominantly sympathetically mediated or sympathetically independent, with variable degrees of sympathetic blockade. In addition, only part of the peripheral circulation is measured with a device which accuracy has not yet been confirmed. Many variables are introduced in this study making a statement that there are no differences between the treatment group and the control somewhat strong. In my opinion: pain relief in complex regional pain syndrome due to spinal cord stimulation may not depend on vasodilatation.     

Epidural Infusion of Opiates and Local Anesthetics for Complex Regional Pain Syndrome

Abstract: Complex Regional Pain Syndrome Type‐I (CRPS‐I) is a neuropathic pain syndrome resulting from complex pain mechanisms that involve several levels and components of the nervous system. CRPS‐I consists of multiple signs, including autonomic dysfunction, in the form of edema, vasomotor changes, motor dysfunctions, muscle spasms, tremors and dystonia, as well as burning pain, hypersensitivity and allodynia that could present in any combination. The treatment is progressive physical therapy rehabilitation program. Multiple analgesic modalities have been used to facilitate the rehabilitation program with varying rates of success. The most successful treatment is a multi‐disciplinary comprehensive approach, where initial pain control allows for physical and psychological interventions that are believed to be the basis for successful treatment. ¹ The pain in CRPS‐I may be mediated through the sympathetic nervous system, sympathetic maintained pain (SMP) or sympathetic independent pain (SIP) ² .     

Assessment of peripheral sympathetic nervous function for diagnosing early post-traumatic complex regional pain syndrome type I

Clinical diagnosis of complex regional pain syndrome type I (CRPS I) in post-traumatic patients is often delayed since the clinical appearance of this disease resembles normal post-traumatic states to a certain extent (pain, edema, loss of function). The purpose of this study was to assess the incidence of specific clinical features in CRPS I patients and normal post-traumatic patients and to evaluate the diagnostic value of a bedside test that measures the sympathetic nervous function. Fifty patients with post-traumatic CRPS I of the upper limb and 50 patients 8 weeks after distal radius fracture with an undisturbed course of disease were subjected to a detailed clinical examination. Pain was assessed using the VAS (visual analog scale), skin temperature measured with an infrared camera and grip-strength with a pneumatic manometer. In CRPS I patients, motor disturbances defined as an impaired active range of motion of the hand, were most frequent (96%, fracture patients: 40%), followed by edema (88%, fracture patients: 80%) and spontaneous pain (VAS 4.0 +/- 2.3, fracture patients: VAS 1.3 +/- 0.6). Systematic temperature differences (>1 degree C) between the affected and unaffected limbs were seen in only 42% of CRPS I patients and in 34% of the fracture patients. Further sensory, sudomotor or trophic changes of the hands were rare. As expected, there were significant differences in the quantity of edema, motor disturbances and sensory disturbances between CRPS I patients and normal fracture patients. However, normal fracture patients still suffered from several of the evaluated symptoms 8 weeks after trauma, which makes an early clinical diagnosis of the complication more difficult. Using a newly developed bedside test, the peripheral sympathetic nervous function was assessed in both groups of patients and in 50 age-matched healthy controls. The decrease in skin blood flow following sympathetic provocation maneuvers, detected by laser Doppler flowmetry, was quantified as sympathetic reactivity. In the affected hands of CRPS I patients, as well as in the contralateral hands, the sympathetic reactivity was obliterated or diminished in contrast to the age-matched controls and normal fracture patients. A multivariate analysis did not reveal any correlation between sympathetic function and the severity of any clinical symptom. Sympathetic reactivity seems to be an independent variable in CRPS I and the test presented may facilitate the difficult clinical diagnosis of this disease.     

Complex regional pain syndromes

Complex regional pain syndromes (CRPS) (formerly reflex sympathetic dystrophy and causalgia) are neuropathic pain conditions that are initiated by an extremity trauma or peripheral nerve lesion. Clinical definition and scientific understanding of CRPS are still evolving; however, both the clinical picture and therapeutic options are significantly influenced by a dysfunction of the sympathetic nervous system. Recent investigations suggest functional central abnormalities and a peripheral inflammatory component in the pathophysiology of CRPS. Interdisciplinary treatment includes physical, pharmacologic, and invasive interventional therapy, as well as stimulation techniques.     

Pathophysiological Mechanisms Involved in Vasomotor Disturbances in Complex Regional Pain Syndrome and Implications for Therapy: A Review

Complex regional pain syndrome (CRPS) is characterized by continuous pain, disproportional to the initial trauma. It usually spreads to the distal parts of the affected limb. Besides continuing pain, a mix of sensory, sudo‐ and vasomotor disturbances, motor dysfunction, and trophic changes is responsible for physical complaints. Vasomotor disturbance is characterized by changes in skin temperature and color. In CRPS patients with a cold extremity, a decrease in blood flow can cause decreased tissue saturation and tissue acidosis, resulting in ischemic pain. The pathophysiology of vasomotor disturbances is not completely understood. Temperature asymmetry is generally assumed as a result of disturbance in the sympathetic nervous system. Vasodilating drugs and sympathetic blockade have been cornerstones of therapy in cold CRPS for years. However, only a limited part of these patients improve on this kind of therapies. Research has shown a pivotal role for inflammation in the pathophysiology of CRPS. Inflammation can result in endothelial dysfunction. Endothelial function plays an important role in the local regulation of vascular tone. Endothelial dysfunction could be another mechanism responsible for the vasomotor disturbances in cold CRPS. An important goal in the treatment of cold‐type CRPS is the restoration of a normal blood flow. Consequently it is important to distinguish the underlying pathophysiological mechanisms of vasomotor disturbances. A disturbance of the sympathetic nervous system may require another type of treatment than inflammation‐induced endothelial dysfunction. Diagnostic tools to distinguish these underlying pathophysiological mechanisms of vasomotor disturbances would enable a mechanism‐based treatment and improve clinical outcome.     

Complex regional pain syndrome

Purpose : This paper provides a review of the current concepts of complex regional pain syndrome (CRPS) and current diagnostic criteria are presented. Etiology and pathophysiological mechanisms of painful disorders, previously addressed as reflex sympathetic dystrophy (RSD) remain doubtful. Issues : The supposition of a sympathetic hyperactivity in the development of this syndrome could not be confirmed. Up to now no diagnostic test that would be specific for the diagnosis of CRPS is available. The diagnosis relies on clinical findings and the exclusion of conditions that could account for the degree of pain and dysfunction. Pain relief and functional restoration are the primary goals of all therapeutic intervention and should start as early as possible.     

Evolving understandings about complex regional pain syndrome and its treatment

Complex regional pain syndrome (CRPS) is still a puzzling disease. Although pathophysiologic understanding has improved, not every aspect of this challenging neuropathic pain syndrome has been explored. Typical symptoms of CRPS are sensory, motor, and autonomic dysfunctions. In most cases, CRPS occurs after a fracture, limb trauma, or lesion of the peripheral or central nervous system. Sometimes, symptoms develop without any trauma. Recent pathophysiologic concepts basically consider three major mechanisms: enhanced peripheral neurogenic inflammation, dysfunction of the sympathetic nervous system, and structural reorganization in the central nervous system. Moreover, a genetic predisposition may explain increased vulnerability. Treatment usually requires a multidisciplinary approach, including medical and nonmedical therapies. The common therapeutic aim is to maintain or restore normal function of the affected extremity. Beyond highlighting pathophysiologic concepts, this article describes recent therapeutic approaches.     

The symptoms of complex regional pain syndrome type 1 alleviated with lamotrigine: A report of 8 cases

Complex regional pain syndrome type 1 (CRPS) comprises the symptom complex of burning nondermatomal pain, intermittent swelling and discoloration, allodynia, and abnormalities of sudomotor function. Not all patients respond to blockade of the sympathetic nervous system. In this case report we highlight 8 cases with intractable CRPS Type 1 in which the patients derived benefit from the use of lamotrigine in terms of both pain relief and relief of other symptoms.     

Complex regional pain syndrome

Purpose : This paper provides a review of the current concepts of complex regional pain syndrome (CRPS) and current diagnostic criteria are presented. Etiology and pathophysiological mechanisms of painful disorders, previously addressed as reflex sympathetic dystrophy (RSD) remain doubtful.

Issues : The supposition of a sympathetic hyperactivity in the development of this syndrome could not be confirmed. Up to now no diagnostic test that would be specific for the diagnosis of CRPS is available. The diagnosis relies on clinical findings and the exclusion of conditions that could account for the degree of pain and dysfunction. Pain relief and functional restoration are the primary goals of all therapeutic intervention and should start as early as possible.     

Complex regional pain syndromes: the influence of cutaneous and deep somatic sympathetic innervation on pain

OBJECTIVES: Complex regional pain syndromes (CRPS) can be relieved by sympathetic blockade. Different sympathetic efferent output channels innervate distinct effector organs (ie, cutaneous vasoconstrictor, muscle vasoconstrictor. and sudomotor neurons, as well as neurons innervating deep somatic tissues like bone, joints, and tendons). The aim of the present study was to elucidate in CRPS patients the sympathetically maintained pain (SMP) component that exclusively depends on cutaneous sympathetic activity compared with the SMP depending on the sympathetic innervation of deep somatic tissues. METHODS: The sympathetic outflow to the painful skin was modulated selectively in awake humans. High and low cutaneous vasoconstrictor activity was produced in 12 CRPS type 1 patients by whole-body cooling and warming (thermal suit). Spontaneous pain was quantified during high and low cutaneous vasoconstrictor activity. By comparing the cutaneous SMP component with the change in pain that was achieved by modulation of the entire sympathetic outflow (sympathetic ganglion block), the SMP component originating in deep somatic structures was estimated. RESULTS: The relief of spontaneous pain after sympathetic blockade was more pronounced than changes in spontaneous pain that could be induced by selective sympathetic cutaneous modulation. The entire SMP component (cutaneous and deep) changes considerably over time. It is most prominent in the acute stages of CRPS. CONCLUSIONS: Sympathetic afferent coupling takes place in the skin and in the deep somatic tissues, but especially in the acute stages of CRPS, the pain component that is influenced by the sympathetic innervation of deep somatic structures is more important than the cutaneous activation. The entire sympathetic maintained pain component is not constant in the course of the disease but decreases over time.     

Lower β-endorphin content of peripheral blood mononuclear cells in patients with complex regional pain syndrome

Recent studies have demonstrated that immune cell-derived β-endorphin inhibits peripheral nociception. Changes in the β-endorphin content of peripheral blood mononuclear cells (PBMC) were also reported in various human disorders. These findings suggest the modulation of pain by immuno-neural interaction through opioid-dependent mechanisms. The aim of this study, therefore, was to determine whether the levels of β-endorphin in PBMC of patients with complex regional pain syndrome (CRPS) differ from those of healthy subjects. Heparinized venous blood was collected from ten CRPS patients (7 women and 3 men; mean age 39.4 ± 13.0 years) and 13 age-matched healthy volunteers (6 women and 7 men; mean age 38.4 ± 10.8 years). PBMC were separated by density gradient centrifugation. β- endorphin was extracted from the cells in a commercial cell lysis buffer and its concentration was measured by enzyme immunoassay technique. Immunoreactive β-endorphin levels in PBMC from the CRPS patients were significantly lower than those from the healthy volunteers (101.5 ± 57.5 versus 222.1 ± 77.6, P < 0.001), and were not correlated to the present pain intensity or pain duration. The results indicate an altered condition of the immune-linked opioid system underlying CRPS. Further immunological approaches may provide new insight into the pathophysiology of CRPS.     

16. Complex Regional Pain Syndrome

Complex regional pain syndrome (CRPS), formerly known as reflex sympathetic dystrophy is a pain syndrome with an unclear pathophysiology and unpredictable clinical course. The disease is often therapy resistant, the natural course not always favorable. The diagnosis of CRPS is based on signs and symptoms derived from medical history and physical examination. Pharmacological pain management and physical rehabilitation of limb function are the main pillars of therapy and should be started as early as possible. If, however, there is no improvement of limb function and persistent severe pain, interventional pain management techniques may be considered. Intravenous regional blocks with guanethidine did not prove superior to placebo but frequent side effects occurred.Therefore this technique receives a negative recommendation (2 A–). Sympathetic block is the interventional treatment of first choice and has a 2 B+ rating. Ganglion stellatum (stellate ganglion) block with repeated local anesthetic injections or by radiofrequency denervation after positive diagnostic block is documented in prospective and retrospective trials in patients suffering from upper limb CRPS. Lumbar sympathetic blocks can be performed with repeated local anesthetic injections. For a more prolonged lumbar sympathetic block radiofrequency treatment is preferred over phenol neurolysis because effects are comparable whereas the risk for side effects is lower (2 B+). For patients suffering from CRPS refractory to conventional treatment and sympathetic blocks, plexus brachialis block or continuous epidural infusion analgesia coupled with exercise therapy may be tried (2 C+). Spinal cord stimulation is recommended if other treatments fail to improve pain and dysfunction (2 B+). Alternatively peripheral nerve stimulation can be considered, preferentially in study conditions (2 C+).     

Pharmacologic treatment of complex regional pain syndrome I: a conceptual framework

Pain may be a leading symptom in complex regional pain syndrome type I (CRPS I) and may hinder functional recovery. In this case, a pharmacotherapeutic approach to pain should be part of the individually tailored interdisciplinary treatment regimen. However, operational criteria for determining which patient may profit from what therapeutic intervention are lacking. This article discusses a conceptual framework in which the rapid progress made in basic pain research may contribute to the clinical management of pain in CRPS I. First, recent insights in the pathophysiologic mechanisms underlying CRPS I are reviewed. CRPS I is considered a neuropathic pain syndrome with a mixed and time-dependent profile of a regional inflammation, sensitization of primary somatosensory afferents (peripheral sensitization), and sensitization of spinal neurons (central sensitization). The dominant mechanisms may vary across individual patients with different time profiles. Second, a model was constructed in which signs and symptoms in an individual patient are related to these mechanisms. Finally, relating the clinical picture to the underlying pathophysiology may help determine the pharmacotherapeutic approach for an individual patient. Pharmacologic options are discussed in this context. The presented framework does not aim to provide an evidence-based treatment algorithm, ready to be used in daily clinical practice; rather it offers a crude, first step toward a mechanism-based pharmacotherapy in CRPS I, in an effort to shift from a mainly empirical treatment paradigm toward theory-driven treatment procedures.     

Complex regional pain syndrome type I associated with amyotrophic lateral sclerosis

BACKGROUND: (CRPS I [formerly called reflex sympathetic dystrophy]) is a syndrome with pain and signs of autonomic dysfunction after trauma or immobilization; the pathophysiologic mechanisms of CRPS I, however, remain unknown. DESIGN: The authors present a case of CRPS I associated with amyotrophic lateral sclerosis. Along with the motor paresis due to amyotrophic lateral sclerosis, pain, swelling, and signs of autonomic disturbance occurred. CONCLUSIONS: This case supports the hypothesis that immobilization is one of the major contributing factors for CRPS I.     

Complex regional pain syndromes—reflex sympathetic dystrophy and causalgia

Reflex sympathetic dystrophy (RSD) was the term applied to a variety of unrelated disorders having strikingly similar clinical features.The problem with the term RSD is that not all cases meet the classical case scenario.The umbrella term Complex Regional Pain Syndromes (CRPS) now includes causalgia and RSD and excludes sympathetically mediated pain, neuropathic pain, inflammatory pain, and phantom pain. Complex Regional Pain Syndromes includes the features of inflammation, autonomic, cutaneous, motor and dystrophic changes which distinguish this from other forms of neuropathic pain. Because the pathophysiology of CRPS is predominantly a hyperactivity of the regional sympathetic nervous system, pain management in such patients should focus on interrupting the activity of the sympathetic nervous system.The interruption can be produced by different modalities classified as pharmacologic, nerve blocks, sympathectomy, physical therapy and psychological therapeutic measures. Physical therapy to regain function is an important endeavor for CRPS patients. In spite of acute and vigorous therapeutic modalities practiced on these patients, early and multidisciplinary treatment holds the best promise.     

Chronic regional pain syndrome, type 1: Part II

Chronic regional pain syndrome, type 1 (CRPS1) is a complex neurologic disease characterized by chronic, severe, burning pain; hyperesthesia; soft tissue swelling; dystrophy; hyperhidrosis; vasomotor and sudomotor instability; joint stiffness; and patchy osteoporosis. Five to six million people in the United States alone suffer from CRPS1. To date, CRPS1 is poorly understood and often is not recognized clinically. This syndrome requires early detection, pain control, and treatment in tandem with physical therapy to the affected area. Part I (published in September) discussed background information on CRPS1 and sympathetic nerve blocks. Part II focuses on the remaining treatment modalities (e.g., sympathectomy, physical therapy, stimulators, trigger point injections, acupuncture, tourniquet effects, placebo effects, amputation).