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.     

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 .     

Sympathetic nervous system and pain--some open questions

Background: Neuropathic pain syndromes may be treated by intervention at the sympathetic nervous system. The pain in these syndromes is therefore called sympathetically maintained pain (SMP). Typical disorders with a SMP component are complex regional pain syndromes (reflex sympathetic dystrophy and causalgia), traumatic neuralgias and herpes zoster. Results: Open questions are how the efferent sympathetic nervous system is capable of influencing pain sensation and which mechanisms underly the autonomic dysregulation often observed in these syndromes. (1) Somatic afferents that project through the sympathetic trunk do not exist. Therefore, a pure sympathetic block does not block afferent information arising from the affected extremity. What alternatives are possible? Under pathophysiological conditions a functional interaction of efferent sympathetic fibers and afferent nociceptive fibers could be demonstrated in patients and animal studies. The intensity of this coupling varies considerably between individual patients and is not necessary for the diagnosis of the disorder. (2) Sympathetical maintained pain and signs of autonomic dysfunction are independent clinical and pathophysiological phenomena without any causal relation. However, it is possible to treat both the SMP and the autonomic dysfunction with sympathetic blocks.     

Pathophysiology and diagnosis in patients with sympathetically dependent pain

Chronic pain in a distal extremity that is accompanied by autonomic dysfunction in the same region is taken to indicate reflex sympathetic dystrophy. Typically, hyperalgesia to light touch is present in addition to the spontaneous pain. The absence of heat hyperalgesia indicates that the underlying mechanism is central rather than peripheral sensitization. This mechanism is similar to that of secondary hyperalgesia in the intact skin surrounding an injury site. Sympathetically maintained pain (SMP) is diagnosed, when these sensory symptoms are reversible under sympathetic blockade. SMP is not due to hyperactivity of sympathetic efferents but to receptor supersensitivity, probably by overexpression of alpha(1)-adrenergic receptors on nociceptive primary afferents. This way normal levels of norepinephrine can cause pathological spontaneous activity of nociceptors which maintains the central sensitization. Chronic burning pain and cutaneous hyperalgesia may also be independent of the sympathetic innervation of the skin. In this case, central sensitization is maintained by other mechanisms. A role of the sympathetic nervous system in the pathogenesis of pain cannot be deduced simply from the simultaneous presence of sensory and autonomic clinical signs and symptoms. Therefore, sympathetic blockade in a patient initially is a diagnostic procedure, aiming to demonstrate the presence of the symptom SMP. Therapeutic blockade is only indicated after this demonstration. For the substantial number of patients with sympathetically independent pain, other treatment modalities are needed which may for example attack central sensitization.     

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.     

Painful neuropathy: altered central processing maintained dynamically by peripheral input.

We performed sensory assessments before and during diagnostic tourniquet-cuff and local anesthetic blocks in 4 patients diagnosed with reflex sympathetic dystrophy (RSD). All patients complained of mechano-allodynia; lightly touching the skin evoked an intense pain sensation. At detection levels, electrical stimuli were perceived as painful, suggesting that the mechano-allodynia was mediated by A beta low-threshold mechanoreceptor afferents. A beta-mediated allodynia was further supported by reaction time latencies to painful electrical stimuli at threshold for A-fiber activation and, in 1 patient, by differential cuff blocks which abolished A beta function and allodynia while thermal sensation (warm and cold) were preserved. Local anesthetic block of painful foci associated with previous trauma abolished mechano-allodynia, cold allodynia, and spontaneous pain in all patients and relieved the motor symptoms in 1 patient with tonic contractures of the toes. Tactile and thermal perception in the previously allodynic area was preserved. When the local anesthetic block waned, spontaneous pain, allodynia, and motor symptoms returned. We propose a model of neuropathic pain in which ongoing nociceptive afferent input from a peripheral focus dynamically maintains altered central processing that accounts for allodynia, spontaneous pain, and other sensory and motor abnormalities. Blocking the peripheral input causes the central processing to revert to normal, abolishing the symptoms for the duration of the block. The model accounts for sympathetically maintained (SMP) and sympathetically independent (SIP) pain. The peripheral input can be independent of sympathetic activity or driven completely or in part by activity in sympathetic efferents or by circulating catecholamines. The shared final common pathway may explain the common features of SMP and SIP.     

Sympathikus und Schmerz: Ideen,Hypothesen, Modelle

In the present article aspects of reflex sympathetic dystrophy (RSD) and sympathetically maintained pain (SMP) are discussed from the point of view of a basic scientist. The main focus is on the sympathetic nervous system. A critical evaluation of the clinical situation is followed by an explanation of the components of a general hypothesis about the mechanisms that might operate in these pain syndromes. This discussion centres on the couplings which might develop between sympathetic and primary afferent neurons, the changes in the neuroeffector transmission to the autonomic effector organs, the role of the micromilieu of the nociceptors and the changes of the central signal in the sympathetic neurons. Finally, clinical observations are discussed that seem to bear little or no relation to the models that are available. The general synopsis puts the problem into a wider context.     

Quantitative sensory tests in patients with neuralgia 11 to 25 years after injury.

In a previous study quantitative sensory tests were used to characterize the symptoms in patients with post-traumatic neuralgia in the hand. Two types of pain syndromes were identified, sympathetically maintained pain (SMP), and sympathetically independent pain (SIP). These two syndromes had different sensory profiles with regard to temperature discrimination and cold and heat pain thresholds. The aim of the present study was to investigate the development of symptoms 10 years later. Eighteen previously investigated patients were contacted and all answered questions concerning their symptoms. Of these, two SIP and eight SMP patients agreed to undergo quantitative sensory testing. The outcome of these tests and the patients' own reports indicated that patients with SMP, who were not repeatedly treated with sympathetic blocks, did not show any remarkable spontaneous improvement of symptoms over a decade. The SMP patients still exhibited their characteristic sensory profile with moderate impairment of temperature discrimination and allodynia to cold, heat and vibratory stimuli. However, some changes with time were observed with respect to warm-cold difference limen and vibration allodynia. Comparison with data obtained from an age-matched group of healthy individuals indicated that these changes were due to age-related factors.     

Intradermal injection of norepinephrine evokes pain in patients with sympathetically maintained pain

Tissue injuries, with or without involvement of nerves, may lead to ongoing pain and hyperalgesia to external stimuli. In a subset of patients, the pain is maintained by sympathetic efferent activity (SMP). We investigated if the peripheral administration of the alpha-adrenergic agonist, norepinephrine (NE), in physiologically relevant doses resulted in pain in patients with SMP. To establish the dose of intradermal NE required to induce cutaneous vasoconstriction, NE (1 nM-10 microM, 30 microl) was injected under a laser Doppler probe on the volar forearm of seven normal subjects. A decrease in blood flow was evident at a dose of 10 microM. Twelve patients (five male, seven female) diagnosed to have SMP based on the decrease in pain by a local anesthetic sympathetic blockade (70+/-6%) were enrolled in the study. Pain ratings were obtained continuously for 5 min after intradermal injections of saline and NE (0.1-10 microM) into their hyperalgesic zone and the mirror-image contralateral side. Injections were done during the period of pain relief following a local anesthetic sympathetic blockade. Similar injections were made in eight control subjects. On the affected side of the patients, the two highest concentrations of NE (1 and 10 microM) caused significantly more pain than saline (P<0.05, ANOVA). In contrast, there was no significant pain induced by the NE injections in the unaffected side and in control subjects. Six of nine patients tested reported a marked decrease in pain and hyperalgesia following infusion of phentolamine (1 mg/kg over 10 min). Two of the three patients who did not receive pain relief following phentolamine infusion also did not report pain to the NE injections. We conclude that NE injections produce pain in SMP patients at doses that are at the threshold for producing vasoconstriction. These studies support a role for cutaneous adrenoceptors in the mechanisms of sympathetically maintained pain.     

Topical application of clonidine relieves hyperalgesia in patients with sympathetically maintained pain.

Patients with reflex sympathetic dystrophy or causalgia characteristically have ongoing pain and pain to light touch (hyperalgesia). Some of these patients obtain relief of their pain following interruption of sympathetic function to the affected area and, therefore, have sympathetically maintained pain (SMP). Evidence suggests that the pain and hyperalgesia in SMP are related to activation of peripheral adrenergic receptors. We wished to determine the contribution of alpha 1- and alpha 2-adrenergic receptors in SMP and thus examined the effects of local application of adrenergic agents in patients with SMP. The alpha 2-adrenergic agonist clonidine, available as a transdermal patch, was delivered topically to the patients' hyperalgesic skin. In four patients with SMP, clonidine eliminated or substantially reduced hyperalgesia to mechanical and cold stimuli. In three of these patients the effects were confined to the skin region beneath the patch, suggesting a peripheral and not central effect. The relief of hyperalgesia was not due to a local anesthetic effect since touch thresholds were unaffected. Topical clonidine did not relieve hyperalgesia of similar severity for two other patients whose hyperalgesia and pain were unaffected by sympathetic ganglion blocks (i.e., diagnosed as having sympathetically independent pain). In two SMP patients, intradermal injection of norepinephrine or phenylephrine (a specific alpha 1-adrenergic agonist) at a site treated with clonidine evoked intense pain and rekindled the pre-clonidine hyperalgesia at that site. It is likely that clonidine locally blocks the release of norepinephrine via activation of alpha 2 receptors on the sympathetic terminals. This study suggests, therefore, that SMP is mediated via alpha 1-adrenergic receptors located in the affected tissue.     

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.     

Dysfonctions du système nerveux sympathique dans la fibromyalgie

Abnormal activity of the sympathetic nervous system is involved in the pathogenesis of protracted pain syndromes. The term sympathetically maintained pain is applied to those neuropathic pain cases that respond to sympatholytic maneuvers. The sympathetically maintained pain concept has strong and ample foundations in the animal model. After nerve injury, sympathetic sprouting at the dorsal root ganglia becomes apparent and form basket-like structures around large-diameter axotomized sensory neurons; sympathetic stimulation can activate such neurons repetitively. This article discusses the relationship between sympathetic dysfunction and chronic pain syndromes, the animal models of sympathetically maintained pain and novel clinical instruments that assess autonomic function. This article also reviews the evidence proposing that fibromyalgia is a sympathetically maintained, neuropathic pain syndrome and finally it discusses therapies that improve resting autonomic tone as well as FM symptoms.     

No effect of sympathetic sudomotor activity on capsaicin-evoked ongoing pain and hyperalgesia

BACKGROUND: Complex regional pain syndromes (causalgia and RSD) can be relieved by blockade of the sympathetic efferent activity. The mechanisms of sympathetically maintained pain (SMP) are unclear. So far an adrenergic interaction between sympathetic vasoconstrictor neurons and nociceptors has been proposed. Alternatively, a cholinergic coupling of sympathetic sudomotor neurons and nociceptors is possible. OBJECTIVE: To determine the effect of cutaneous sympathetic sudomotor activity on pain induced by primary afferent C-nociceptor activation with capsaicin in humans. METHODS: In 10 healthy volunteers capsaicin was injected into the forearm skin to induce ongoing pain and dynamic and punctate mechanical hyperalgesia. Intensity of pain and hyperalgesia and area of hyperalgesia (planimetry) were assessed. The local skin temperature at the application and measurement sites was kept constant at 35 degrees C. In each individual the analyses were performed during the presence of low and high sympathetic sudomotor skin activity induced by whole-body temperature changes with a thermal suit. By altering whole-body temperature from a moderately warm to an intensely warm state, sympathetic sudomotor activity is modulated selectively in the widest range that can be achieved physiologically while sympathetic vasoconstrictor activity is continuously inhibited. The degree of sudomotor discharge was monitored by measuring cutaneous sweat production at the forearm with the colour indicator ponso-red. The inhibition of vasocontrictor discharge was monitored by measuring cutaneous blood flow at the index finger with laser Doppler flowmetry. RESULTS: The intensity and spatial distribution of capsaicin-evoked ongoing pain and dynamic and punctate mechanical hyperalgesia were not significantly different during the presence of high and low sympathetic sudomotor discharge. Conclusions: Cutaneous sympathetic sudomotor activity does not influence capsaicin induced pain and mechanical hyperalgesia.     

Bilateral burning foot pain: monitoring of pain, sensation, and autonomic function during successful treatment with sympathetic blockade

We describe a patient with burning pain in both feet associated with local autonomic disturbances following bilateral traumatic sciatic mononeuropathies. The diagnosis of a sympathetically maintained pain was confirmed through a prompt response to sympathetic blockade. Although a mild alcohol-nutritional neuropathy was found, the clinical findings strongly suggested a diagnosis of bilateral causalgia. Clinical evaluation and quantitative sensory testing were performed prior to and after successive unilateral lumbar sympathetic nerve blocks. After unilateral blockade, bilateral improvement was recorded in measures of pain, sudomotor function, and foot temperature. Other measures of autonomic function showed variable responses to sympathetic blockade. Quantitative sensory testing revealed a dramatic alteration in the contralateral limb's thermal sense following unilateral block. This case underscores the potential for bilateral causalgia and provides additional evidence for a central mechanism operating in this disorder. The relationship between bilateral causalgia and the "burning feet syndrome" in alcoholic neuropathy is discussed.     

Catecholamine-induced excitation of nociceptors in sympathetically maintained pain

Sympathetically maintained pain could either be mediated by ephaptic interactions between sympathetic efferent and afferent nociceptive fibers or by catecholamine-induced activation of nociceptive nerve endings. We report here single fiber recordings from C nociceptors in a patient with sympathetically maintained pain, in whom sympathetic blockade had repeatedly eliminated the ongoing pain in both legs. We classified eight C-fibers as mechano-responsive and six as mechano-insensitive nociceptors according to their mechanical responsiveness and activity-dependent slowing of conduction velocity (latency increase of 0.5+/-1.1 vs. 7.1+/-2.0 ms for 20 pulses at 0.125 Hz). Two C-fibers were activated with a delay of several seconds following strong endogenous sympathetic bursts; they were also excited for about 3 min following the injection of norepinephrine (10 microl, 0.05%) into their innervation territory. In these two fibers, a prolonged activation by injection of low pH solution (phosphate buffer, pH 6.0, 10 microl) and sensitization of their heat response following prostaglandin E2 injection were recorded, evidencing their afferent nature. Moreover, their activity-dependent slowing was typical for mechano-insensitive nociceptors. We conclude that sensitized mechano-insensitive nociceptors can be activated by endogenously released catecholamines and thereby may contribute to sympathetically maintained pain. No evidence for ephaptic interaction between sympathetic efferent and nociceptive afferent fibers was found.     

Fibromyalgia as a sympathetically maintained pain syndrome

Abnormal activity of the sympathetic nervous system may be involved in the pathogenesis of chronic pain syndromes. This article reviews the animal studies of sympathetically induced pain behavior, the controversy of sympathetically maintained pain in clinical practice, and the dysautonomic nature of fibromyalgia (FM). FM has neuropathic pain features (stimuli-independent pain state accompanied by allodynia and paresthesias). The proposal of FM as a sympathetically maintained pain syndrome is based on the controlled studies showing that patients with FM display signs of relentless sympathetic hyperactivity and that the pain is submissive to sympathetic blockade and is rekindled by norepinephrine injections. Dysautonomia also may explain the multisystem features of FM.     

Complex regional pain syndrome

Complex regional pain syndrome (CRPS), formerly known as reflex sympathetic dystrophy, is a regional, posttraumatic, neuropathic pain problem that most often affects 1 or more limbs. Like most medical conditions, early diagnosis and treatment increase the likelihood of a successful outcome. Accordingly, patients with clinical signs and symptoms of CRPS after an injury should be referred immediately to a physician with expertise in evaluating and treating this condition. Physical therapy is the cornerstone and first-line treatment for CRPS. Mild cases respond to physical therapy and physical modalities. Mild to moderate cases may require adjuvant analgesics, such as anticonvulsants and/or antidepressants. An opioid should be added to the treatment regimen if these medications do not provide sufficient analgesia to allow the patient to participate in physical therapy. Patients with moderate to severe pain and/or sympathetic dysfunction require regional anesthetic blockade to participate in physical therapy. A small percentage of patients develop refractory, chronic pain and require long-term multidisciplinary treatment, including physical therapy, psychological support, and pain-relieving measures. Pain-relieving measures include medications, sympathetic/somatic blockade, spinal cord stimulation, and spinal analgesia.     

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.     

Defining the therapeutic role of local anesthetic sympathetic blockade in complex regional pain syndrome: a narrative and systematic review

OBJECTIVE: There is growing controversy on the value of blocking the sympathetic nervous system for the treatment of complex regional pain syndromes (CRPS). The authors sought to evaluate the efficacy of sympathetic blockade with local anesthetic in these syndromes. In addition, they performed a comprehensive review of the pathophysiology and other treatments for CRPS. DESIGN: Systematic review of the literature was performed. MEDLINE was searched from 1966 through 1999. The authors identified only three randomized controlled trials (RCTs) that evaluated sympathetic blockade with local anesthetic, but because of differences in study design they were unable to pool the study data. The authors therefore included nonrandomized studies and case series. INTERVENTIONS: Studies were included if local anesthetic sympathetic blockade was used in at least 10 patients. Studies were excluded if continuous infusion techniques, somatic nerve blocks, or combined sympatholytic therapies were evaluated. OUTCOME MEASURES: Pain relief was classified as full, partial, or absent. The lack of a comparison group in the studies allowed only the calculation of distribution of the response categories, and the sum of the pooled rates does not equal 100%. RESULTS: Twenty-nine studies were included that evaluated 1,144 patients. Nineteen studies were retrospective, 5 prospective case series, 3 RCTs, and 2 nonrandomized controlled studies. The quality of the publications was generally poor. Twenty-nine percent of patients had full response, 41% had partial response, and 32% had absent response. It was not possible to estimate the duration of pain relief. CONCLUSIONS: This review raises questions as to the efficacy of local anesthetic sympathetic blockade as treatment of CRPS. Its efficacy is based mainly on case series. Less than one third of patients obtained full pain relief. The absence of control groups in case series leads to an overestimation of the treatment response that can explain the findings.     

Complex regional pain syndrome: a review of diagnostics, pathophysiologic mechanisms, and treatment implications for certified registered nurse anesthetists

The pathophysiologic mechanisms for complex regional pain syndrome (CRPS) are complex and elusive. The proposed etiologic mechanisms for CRPS include inflammatory responses, peripheral or central sensitization, and sympathetic dysfunction. Anesthesia care of patients with CRPS is challenging. Treatments including physiotherapy, peripheral vasodilators, sympathetic blockade, analgesics, and other systemic medications can help optimize mobility, perfusion, and pain relief for affected patients.