Chronic Complex Regional Pain Syndrome Patients Research Articles

Healthcare Costs, Time to Fitness for Work, and Related Factors in Chronic Complex Regional Pain Syndrome: A Comparative and Longitudinal Study of 5-Year Follow-Up.

To assess and compare the healthcare costs, time to fitness for work (TFW) between chronic complex regional pain syndrome (CRPS) and non-CRPS; and identify factors associated with these outcomes in a comparative longitudinal study. 148 patients with chronic CRPS of the hand and 273 patients with chronic hand impairments but without CRPS (non-CRPS) were admitted at a Swiss rehabilitation clinic between 2007 and 2016. Healthcare costs and TFW were retrieved from insurance data over 5 years after the accident. Socio-demographic factors, biopsychosocial complexity measured by means of the INTERMED questionnaire, pain intensity and DASH disability scores were collected during rehabilitation. Generalized estimation equations and Cox proportional-hazards models were used to identify factors associated with outcomes. Healthcare costs were increased by 20% for the CRPS versus non-CRPS group (coefficient = 1.20, 95% CI = 1.08-1.35, p<0.001). The median TFW was longer for CRPS than non-CRPS patients (816 vs 672 days, p = 0.02). After adjusting for covariates, TFW did not differ between the two groups (hazard ratio = 0.94, 95% CI = 0.73-1.21, p=0.61). For CRPS patients, higher healthcare costs were associated with severe or moderate initial injury, high INTERMED or DASH disability scores. Longer TFW were associated with severe initial injury, low educational level, no work contract, and high INTERMED or DASH disability scores. Overall, the healthcare costs were higher for CRPS than non-CRPS patients, but the TFW was comparable. We demonstrated also the significant associations of disability and biopsychosocial factors with the healthcare costs and TFW in CRPS patients.

Modifications in fMRI Representation of Mental Rotation Following a 6 Week Graded Motor Imagery Training in Chronic CRPS Patients

Complex regional pain syndrome (CRPS) is a neuropathic pain condition that is difficult to treat. For behavioral interventions, graded motor imagery (GMI) showed relevant effects, but underlying neural substrates in patient groups have not been investigated yet. A previous study investigating differences in the representation of a left/right hand judgment task demonstrated less recruitment of subcortical structures, such as the putamen, in CRPS patients than in healthy controls. In healthy volunteers, the putamen activity increased after a hand judgment task training. In order to test for longitudinal effects of GMI training, we investigated 20 CRPS patients in a wait-list crossover design with 3 evaluation time points. Patients underwent a 6 week GMI treatment and a 6 week waiting period in a randomized group assignment and treatment groups were evaluated by a blinded rater. When compared to healthy matched controls at baseline, CRPS patients showed less functional activation in areas processing visual input, left sensorimotor cortex, and right putamen. Only GMI treatment, but not the waiting period showed an effect on movement pain and hand judgment task performance. Regression analyses revealed positive associations of movement pain with left anterior insula activation at baseline. Right intraparietal sulcus activation change during GMI was associated with a gain in performance of the hand judgment task. The design used here is reliable for investigating the functional representation of the hand judgment task in an intervention study. PerspectiveTwenty chronic CRPS patients underwent a 6 week GMI intervention in a randomized wait-list crossover design. functional MRI was tested pre and post for the hand lateralization task which improved over GMI but not over WAITING. Performance gain was positively related to right parietal functional MRI activation.

Psychological Characteristics in Patients with Chronic Complex Regional Pain Syndrome: Comparisons with Patients with Major Depressive Disorder and Other Types of Chronic Pain.

ObjectiveThis study investigated psychological characteristics of patients with chronic complex regional pain syndrome (CRPS) and examined relationships between psychosocial factors and pain severity.MethodsIn total, 76 patients with CRPS, 95 patients with other types of chronic pain, 171 healthy controls, and 66 patients with major depressive disorder (MDD) were included. Minnesota Multiphasic Personality Inventory (MMPI-2) profiles and scores on the Beck Depression Inventory and State–Trait Anxiety Inventory were calculated. Pain intensity was measured using a visual analog scale (VAS).ResultsPatients with CRPS scored higher on the Hypochondriasis (Hs), Depression (D), Hysteria (Hy), Paranoia (Pa), and Psychasthenia (Pt) scales of the MMPI-2 compared to healthy controls. The CRPS group scored lower on the D, Psychopathic deviate (Pd), Pa, Pt, Schizophrenia (Sc), and Social introversion (Si) scales compared to the MDD group. Although CRPS patients reported higher levels of pain than patients with other types of pain, the MMPI profiles of the two pain groups did not differ significantly. Linear regression analyses revealed that pain severity was significantly associated with depression and scores on the Masculinity–Femininity (Mf) scale.ConclusionThis is the first comparative study of the psychological characteristics of chronic CRPS patients, healthy controls, and patients with MDD. The neurotic profiles of CRPS patients were more psychologically adaptable than were those of patients with MDD; however, this profile was shared by both pain groups. The present findings further showed that, although pain severity was not a major contributor to depression, patients with CRPS should be evaluated for depressive symptoms.

Implications of the putamen in pain and motor deficits in complex regional pain syndrome.

Complex regional pain syndrome (CRPS) develops after-limb injury, with persistent pain and deficits in movement frequently co-occurring. The striatum is critical for mediating multiple mechanisms that are often aberrant in CRPS, which includes sensory and pain processing, motor function, and goal-directed behaviors associated with movement. Yet, much remains unknown with regards to the morphological and functional properties of the striatum and its subregions in this disease. Thus, we investigated 20 patients (15 female, age 58 ± 9 years, right-handed) diagnosed with chronic (6+ months of pain duration) CRPS in the right hand and 20 matched, healthy controls with anatomical and resting-state, functional magnetic resonance imaging. In addition, a comprehensive clinical and behavioral evaluation was performed, where each participant's pain, motor function, and medical history were assessed. Complex regional pain syndrome patients harbored significant abnormalities in hand coordination, dexterity, and strength. These clinical pain- and movement-related findings in CRPS patients were concomitant with bilateral decreases in gray matter density in the putamen as well as functional connectivity increases and decreases among the putamen and pre-/postcentral gyri and cerebellum, respectively. Importantly, higher levels of clinical pain and motor impairment were associated with increased putamen-pre-/postcentral gyri functional connectivity strengths. Collectively, these findings suggest that putaminal alterations, specifically the functional interactions with sensorimotor structures, may underpin clinical pain and motor impairment in chronic CRPS patients.

Diurnal and Nocturnal Skin Temperature Regulation in Chronic Complex Regional Pain Syndrome

Skin temperature changes due to vasomotor disturbances are important features of complex regional pain syndrome (CRPS). Because this phenomenon has only been studied under controlled conditions, information on daily circadian variability is lacking. Also, studies in chronic CRPS patients with abnormal posturing, in which coldness of the affected extremity is more common, do not exist. We examined the response to external heating as well as circadian temperature changes over several days in the affected legs of 14 chronic CRPS patients with abnormal posturing and 17 controls. Skin temperatures were recorded hourly for 14 days using wireless sensors. Although the patients' affected extremities were significantly colder before external heating, the vasodilatory response was similar in the 2 groups. Additionally, median skin temperature differences between both legs and their variability was larger in patients than in controls during the day, but not during the night. These findings indicate that the mechanisms underlying impaired skin circulation in CRPS during daytime are reversible under certain circumstances. The large variation in skin temperature differences during the day questions the validity of using a single measurement in the diagnosis of CRPS, and our results indicate that only temperature differences >1.0°C should be considered to reflect vasomotor disturbances. PerspectiveThis article shows that chronic CRPS patients have a normal vasodilatory response to external heating and that skin temperature differences between the affected and unaffected lower limbs, which were highly variable during daytime, disappeared during sleep. This indicates that part of the vasomotor regulation in these patients is still functional.

Force modulation deficits in complex regional pain syndrome: A potential role for impaired sense of force production

Compelling evidence points at both impaired proprioception and disturbed force control in patients with chronic complex regional pain syndrome (CRPS). Because force modulation at least partly relies on proprioception, we evaluated if impaired sense of force production contributes to disturbances of force control in patients with CRPS. Characteristics of voluntary force modulation were examined in the affected upper extremity in 28 CRPS patients with abnormal postures, in 12 CRPS patients without abnormal postures, and in 32 healthy controls. Isometric grip-force matching was compared between conditions with and without visual feedback to identify potential deficits in the sense of force production in terms of force reproduction errors. Voluntary force modulation was impaired in CRPS patients, but more so in patients with abnormal postures. In particular, CRPS patients with abnormal postures were characterized by reduced maximum force, reduced ability to increase force output according to task instructions, higher variability of force output and less adequate correction of deviations from the target force. Although effects of visual feedback removal appeared largely similar for the two patient groups and controls, our findings with respect to force reproduction errors suggested that an impaired sense of force production may contribute to the motor dysfunction in CRPS. CRPS patients, in particular those with abnormal postures, showed impaired voluntary force control and an impaired sense of force production. This suggests that therapeutic strategies aimed at restoration of proprioceptive impairments, possibly using online visual feedback, may promote the recovery of motor function in CRPS.

A CRPS-IgG-transfer-trauma model reproducing inflammatory and positive sensory signs associated with complex regional pain syndrome

The aetiology of complex regional pain syndrome (CRPS), a highly painful, usually post-traumatic condition affecting the limbs, is unknown, but recent results have suggested an autoimmune contribution. To confirm a role for pathogenic autoantibodies, we established a passive-transfer trauma model. Prior to undergoing incision of hind limb plantar skin and muscle, mice were injected either with serum IgG obtained from chronic CRPS patients or matched healthy volunteers, or with saline. Unilateral hind limb plantar skin and muscle incision was performed to induce typical, mild tissue injury. Mechanical hyperalgesia, paw swelling, heat and cold sensitivity, weight-bearing ability, locomotor activity, motor coordination, paw temperature, and body weight were investigated for 8days. After sacrifice, proinflammatory sensory neuropeptides and cytokines were measured in paw tissues. CRPS patient IgG treatment significantly increased hind limb mechanical hyperalgesia and oedema in the incised paw compared with IgG from healthy subjects or saline. Plantar incision induced a remarkable elevation of substance P immunoreactivity on day 8, which was significantly increased by CRPS-IgG. In this IgG-transfer-trauma model for CRPS, serum IgG from chronic CRPS patients induced clinical and laboratory features resembling the human disease. These results support the hypothesis that autoantibodies may contribute to the pathophysiology of CRPS, and that autoantibody-removing therapies may be effective treatments for long-standing CRPS.

1H-NMR metabolic profiling of cerebrospinal fluid in patients with complex regional pain syndrome–related dystonia

In complex regional pain syndrome (CRPS)-related dystonia, compelling evidence points to the involvement of the central nervous system, but the underpinning pathobiology is still unclear. Thus, to enable a hypothesis-free, unbiased view of the problem and to obtain new insight into the pathobiology of dystonia in CRPS, we applied an exploratory metabolomics analysis of cerebrospinal fluid (CSF) of patients with CRPS-related dystonia. 1H-NMR spectroscopy in combination with multivariate modeling were used to investigate metabolic profiles of a total of 105 CSF samples collected from patients with CRPS-related dystonia and controls. We found a significantly different metabolic profile of CSF in CRPS patients compared to controls. The differences were already reflected in the first two principal components of the principal component analysis model, which is an indication that the variance associated with CRPS is stronger than variance caused by such classical confounders as gender, age, or individual differences. A supervised analysis generated a strong model pinpointing the most important metabolites contributed to the metabolic signature of patients with CRPS-related dystonia. From the set of identified discriminators, the most relevant metabolites were 2-keto-isovalerate, glucose, glutamine, and lactate, which all showed increased concentrations, and urea, which showed decreased concentration in CRPS subjects. Our findings point at a catabolic state in chronic CRPS patients with dystonia that is likely associated with inflammation.

Motor Dysfunction of Complex Regional Pain Syndrome Is Related to Impaired Central Processing of Proprioceptive Information

Our understanding of proprioceptive deficits in complex regional pain syndrome (CRPS) and its potential contribution to impaired motor function is still limited. To gain more insight into these issues, we evaluated accuracy and precision of joint position sense over a range of flexion-extension angles of the wrist of the affected and unaffected sides in 25 chronic CRPS patients and in 50 healthy controls. The results revealed proprioceptive impairment at both the patients' affected and unaffected sides, characterized predominantly by overestimation of wrist extension angles. Precision of the position estimates was more prominently reduced at the affected side. Importantly, group differences in proprioceptive performance were observed not only for tests at identical percentages of each individual's range of wrist motion but also when controls were tested at wrist angles that corresponded to those of the patient's affected side. More severe motor impairment of the affected side was associated with poorer proprioceptive performance. Based on additional sensory tests, variations in proprioceptive performance over the range of wrist angles, and comparisons between active and passive displacements, the disturbances of proprioceptive performance most likely resulted from altered processing of afferent (and not efferent) information and its subsequent interpretation in the context of a distorted “body schema.” PerspectiveThe present results point at a significant role for impaired central processing of proprioceptive information in the motor dysfunction of CRPS and suggest that therapeutic strategies aimed at identification of proprioceptive impairments and their restoration may promote the recovery of motor function in CRPS patients.

Deficient muscle activation in patients with Complex Regional Pain Syndrome and abnormal hand postures: An electromyographic evaluation

ObjectiveMotor abnormalities in Complex Regional Pain Syndrome (CRPS) are common and often characterized by a restricted active range of motion (AROM) and an increased resistance to passive movements, whereby the affected body part preferably adopts an abnormal posture. The objective of the present study was to obtain a better understanding of the factors that are associated with these abnormal postures and limitations of the AROM, and to investigate whether these motor impairments reflect dystonia. MethodsWe evaluated characteristics of surface EMG of the flexor carpi radialis and extensor carpi radialis muscles during active maintenance of various flexion–extension postures of the wrist of the affected and unaffected side in 15 chronic CRPS patients, and in 15 healthy controls. ResultsDeviant joint postures in chronic CRPS – at least in those patients with some range of active movement – were not characterized by sustained muscle contractions, and limitations of the AROM were not attributable to excessive co-contraction. Rather, the agonistic muscle and its antagonist were activated in normal proportions, albeit over a limited range. ConclusionsThe AROM limitations and abnormal postures that are often observed in chronic CRPS patients are not associated with excessive muscle activity and hence do not exhibit the characteristics typical of dystonia. SignificanceWe hypothesize that structural alterations in skeletal muscle tissue and pain-induced adaptations of motor function may contribute to the observed motor impairments. Our findings may have important clinical implications, since commonly prescribed treatments are aimed at reducing excessive muscle contraction.

Cutaneous noradrenaline measured by microdialysis in complex regional pain syndrome during whole-body cooling and heating

Complex regional pain syndrome (CRPS) is characterised by autonomic, sensory, and motor disturbances. The underlying mechanisms of the autonomic changes in CPRS are unknown. However, it has been postulated that sympathetic inhibition in the acute phase with locally reduced levels of noradrenaline is followed by an up-regulation of alpha-adrenoceptors in chronic CRPS leading to denervation supersensitivity to catecholamines. This exploratory study examined the effect of cutaneous sympathetic activation and inhibition on cutaneous noradrenaline release, vascular reactivity, and pain in CRPS patients and in healthy volunteers. Seven patients and nine controls completed whole-body cooling (sympathetic activation) and heating (sympathetic inhibition) induced by a whole-body thermal suit with simultaneous measurement of the skin temperature, skin blood flow, and release of dermal noradrenaline. CRPS pain and the perceived skin temperature were measured every 5min during thermal exposure, while noradrenaline was determined from cutaneous microdialysate collected every 20min throughout the study period. Cooling induced peripheral sympathetic activation in patients and controls with significant increases in dermal noradrenaline, vasoconstriction, and reduction in skin temperature. The main findings were that the noradrenaline response did not differ between patients and controls or between the CRPS hand and the contralateral unaffected hand, suggesting that the evoked noradrenaline release from the cutaneous sympathetic postganglionic fibres is preserved in chronic CRPS patients.

Efficacy and safety of a single intrathecal methylprednisolone bolus in chronic complex regional pain syndrome

Activated immune cells in the spinal cord may play an important role in the development and maintenance of neuropathic pain, such as occurs in response to peripheral inflammation or tissue injury. Immune activation may therefore serve as a therapeutic target for immune modulating drugs like corticosteroids. This double-blind randomized placebo-controlled parallel-group trial aimed to investigate the efficacy and safety of a single intrathecal administration of 60 mg methylprednisolone (ITM) in chronic patients with complex regional pain syndrome (CRPS). The primary outcome measure was change in pain (pain intensity numeric rating scale; range 0–10) after 6 weeks. With 21 subjects per group the study had a 90% power to detect a clinically relevant difference (⩾2 points). After 21 patients (10 on ITM) were included, the trial was stopped prematurely after the interim analysis had shown that ITM had no effect on pain (difference in mean pain intensity numeric rating scale at 6 weeks 0.3, 95% confidence interval −0.7 to 1.3) or any other outcome measure. We did not find any difference in treatment-emergent adverse events between the ITM and placebo group. We conclude that a single bolus administration of ITM is not efficacious in chronic CRPS patients, which may indicate that spinal immune activation does not play an important role in this phase of the syndrome.

No Recovery of Cold Complex Regional Pain Syndrome After Transdermal Isosorbide Dinitrate: A Small Controlled Trial

The microcirculation appears to be impaired in cold chronic complex regional pain syndrome (CRPS). This double-blind, placebo-controlled, randomized trial investigated the effect of the nitric oxide (NO) donor isosorbide dinitrate (ISDN) on the peripheral blood flow in patients with chronic CRPS. Twenty-four patients received 1% ISDN in Vaseline ® or a placebo ointment applied to the dorsum of the affected hand four times daily for 10 weeks. The patients participated in a physical therapy program to improve activity. The primary outcome measure was blood distribution in the affected extremity, which was determined by measuring the skin temperature using videothermography. We also measured NO and endothelin-1 concentrations in blister fluid, pain using the visual analog scale, and activity limitations using an upper limb activity monitor and the Disabilities of Arm Shoulder and Hand Questionnaire. ISDN failed to produce a significant improvement in temperature asymmetry in chronic cold CRPS patients, and it did not result in the expected reduction in pain and increase in activity compared with placebo either. There may be other central or peripheral factors contributing to the disturbed vasodynamics in cold chronic CRPS that are not influenced by NO substitution. This study does not show an improvement of the regional blood distribution by ISDN in the involved extremity of patients with cold-type CRPS.

The Brain in Chronic CRPS Pain: Abnormal Gray-White Matter Interactions in Emotional and Autonomic Regions

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.

Central processing of tactile and nociceptive stimuli in complex regional pain syndrome

Objective Patients with complex regional pain syndrome (CRPS) suffer from continuous regional limb pain and from hyperesthesia to touch and pain. To better understand the pathophysiological mechanisms underlying the hyperesthesia of CRPS patients, we investigated their cortical processing of touch and acute pain. Methods Cortical responses to tactile stimuli applied to the thumbs, index and little fingers (D1, D2, and D5) and nociceptive stimuli delivered to dorsa of the hands were recorded with a whole-scalp neuromagnetometer from eight chronic CRPS patients and from nine healthy control subjects. Results In the patients, primary somatosensory (SI) cortex activation to tactile stimulation of D2 was significantly stronger, and the D1–D5 distance in SI was significantly smaller for the painful hand compared to the healthy hand. The PPC activation to tactile stimulation was significantly weaker in the patients than in the control subjects. To nociceptive stimulation with equal laser energy, the secondary somatosensory (SII) cortices and posterior parietal cortex (PPC) were similarly activated in both groups. The PPC source strength correlated with the pain rating in the control subjects, but not in the patients. Conclusions The enhanced SI activation in hyperesthetic CRPS patients may reflect central sensitization to touch. The decreased D1–D5 distance implies permanent changes in SI hand representations in chronic CRPS. The defective PPC activation could be associated with the neglect-like symptoms of the patients. As the SII and PPC responses were not enhanced in the CRPS patients, other brain areas are likely to contribute to the observed hyperesthesia to pain. Significance Our results indicate changes of somatosensory processing at cortical level in CRPS.

Analysis of Cerebrospinal Fluid Inflammatory Mediators in Chronic Complex Regional Pain Syndrome Related Dystonia

There is compelling evidence of central nervous system involvement in neuropathic pain and movement disorders in patients with complex regional pain syndrome (CRPS). Previously, elevated cerebrospinal fluid (CSF) levels of interleukin-1beta and interleukin-6 were found in CRPS patients with and without movement disorders. The aim of the present study was to replicate these findings and to search for additional CSF biomarkers in chronic CRPS patients with dystonia. CSF samples of 20 patients and 29 controls who underwent spinal anesthesia for surgical interventions participated. We measured interleukin-1beta, interleukin-6, interferon-gamma inducible protein-10, RANTES (regulated upon activation, normal T-cell expressed and secreted), complement C3, mannose-binding lectin, complement C1q, soluble intercellular adhesion molecule-1, endothelin-1, nitric oxide, human lactoferrin, and hypocretin-1 levels in these samples. No differences in the CSF levels of these effector mediators between patients and controls were found. Our CSF findings do not support a role of a variety of inflammatory mediators or hypocretin-1 in chronic CRPS patients with dystonia.

Psychological abnormalities in patients with complex regional pain syndrome (CRPS)

Do comorbid psychological disorders, dysfunctional pain processing, and psychosocial pain coping occur with complex regional pain syndrome (CRPS) and is a connection between clinical and psychological manifestations apparent? In addition to securing information on case histories and performing clinical neurological examinations of chronic CRPS patients, the structured clinical interview (SCID), pain perception scale, and the Kiel Pain Inventory were employed. The structured clinical interview revealed evidence of a depressive episode in 65% of CRPS patients. Pain perception is similar to neuropathic pain syndromes and patient history revealed a slightly increased frequency of anxiety and affective disorders. Depressive syndrome occurred significantly more often in right-sided CRPS; otherwise, there were no significant correlations between medical history, clinical examination, and frequency of psychological disorders. However, CRPS patients with allodynia manifest clinical signs of special psychological distress. In chronic CRPS depressive syndrome frequently develops and psychological treatment can be recommended.

Chronic pain patients are impaired on an emotional decision-making task

Chronic pain can result in anxiety, depression and reduced quality of life. However, its effects on cognitive abilities have remained unclear although many studies attempted to psychologically profile chronic pain. We hypothesized that performance on an emotional decision-making task may be impaired in chronic pain since human brain imaging studies show that brain regions critical for this ability are also involved in chronic pain. Chronic back pain (CBP) patients, chronic complex regional pain syndrome (CRPS) patients, and normal volunteers (matched for age, sex, and education) were studied on the Iowa Gambling Task, a card game developed to study emotional decision-making. Outcomes on the gambling task were contrasted to performance on other cognitive tasks. The net number of choices made from advantageous decks after subtracting choices made from disadvantageous decks on average was 22.6 in normal subjects ( n=26), 13.4 in CBP patients ( n=26), and −9.5 in CRPS patients ( n=12), indicating poor performance in the patient groups as compared to the normal controls ( P<0.004). Only pain intensity assessed during the gambling task was correlated with task outcome and only in CBP patients ( r=−0.75, P<0.003). Other cognitive abilities, such as attention, short-term memory, and general intelligence tested normal in the chronic pain patients. Our evidence indicates that chronic pain is associated with a specific cognitive deficit, which may impact everyday behavior especially in risky, emotionally laden, situations.

Complex regional pain syndrome (reflex sympathetic dystrophy and causalgia): management with the calcium channel blocker nifedipine and/or the α-sympathetic blocker phenoxybenzamine in 59 patients

Complex Regional Pain Syndrome (CRPS) is the new name for entities formerly known mostly as Reflex Sympathetic Dystrophy and Causalgia. Treatment of CRPS with either the calcium channel blocker nifedipine or the α-sympathetic blocker phenoxybenzamine was assessed in 59 patients, 12 with early stages of CRPS, 47 with chronic stage CRPS. In the early stage CRPS patients, 3 of 5 were cured with nifedipine and 8 of 9 (2 of whom had earlier received nifedipine) with phenoxybenzamine, for a cure rate of 92% (11 out of 12). In the chronic stage CRPS patients, 10 of 30 were cured with nifedipine; phenoxybenzamine cured 7 of 17 patients when administered as a first choice and another 2 ofof 7 patients who received nifedipine earlier, for a total late stage success rate of 40% (19 out of 47). The most common side effects necessitating discontinuing the drug were headaches for nifedipine and orthostatic dizziness, nausea and diarrhoea for phenoxybenzamine. All male patients on phenoxybenzamine experienced impotence, but this did not lead to discontinuing this agent and immediately disappeared after stopping the drug. These results once again stress the importance of early recognition of CRPS, and treatment with either of these drugs could be considered as a first choice for early CRPS, especially because in this series this treatment was not combined with physical therapy making it very cost-effective. In the chronic stage of CRPS, treatment with these drugs was much less successful (40%), even though it was always combined with physical therapy, but it can still be considered, either as a first choice or when other types of treatment have failed.