Near-infrared Spectroscopic Measurement in Complex Regional Pain Syndrome

Study Overview
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Brief Summary
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Recent clinical investigations have suggested that the cause of abnormal pain in complex regional pain syndrome could be ischemia and inflammation, due to poor blood flow to deep tissues from microvascular pathology. This study aims to determine if a new technology called near infrared spectroscopy can measure this microvascular dysfunction. The study hypothesizes that significant differences can be measured in the microcirculation of patients with CRPS-I using near infrared spectroscopy and the vascular occlusion test.

Detailed Description
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The pathophysiology of CRPS-1 is unknown yet a considerable number of studies suggest that the fundamental cause of abnormal pain is due to microvascular pathology of deep tissues. Reduced blood flow to deep tissues such as muscle, nerve, and bone can lead to a combination of inflammatory and neuropathic pain processes (Coderre TJ et al. 2010). Evidence to support this model of microcirculatory dysfunction includes observations that skin capillary oxygenation is decreased and skin lactate is increased in affected limbs of patients (total of 11 patients in lactate study) (Birklein F et al. 2000, Manahan AP et al. 2007). It has also been reported that patients with CRPS-I have abnormal vasodilatory responses after sympathetically-mediated vasoconstriction (Dayan L et al. 2008) and decreased concentrations of nitric oxide in the affected limb (Groeneweg JG et al. 2006). Near-infrared spectroscopy (NIRS) is a non-invasive method of measuring tissue oxygenation using the differential absorption properties of oxygenated and deoxygenated hemoglobin in biological tissue (Creteur J 2008). Near-infrared light is only transmitted through small vessels with diameter less than 1 mm (arterioles, venules and capillaries). Since NIRS is limited to monitoring only small vessels, it can be used to assess oxygen balance in the microcirculation of skeletal muscle (Creteur J 2008). Premises Premise 1: Complex regional pain syndrome is associated with microcirculatory dysfunction After an injury to a patient's limb, it is hypothesized that the pressure exerted by that swelling within a relatively confined anatomical space can occlude the capillaries of adjacent tissues and cause a compartment syndrome-like injury. Coderre et al. (2010) have theorized that the resulting microcirculatory dysfunction causes a persistent inflammatory state which is then responsible for pain generation. In an animal model of ischemia-reperfusion injury used to study CRPS-1, microscopy of muscle and nerve tissue demonstrates microvascular evidence of a slow-flow/no-reflow phenomenon (Coderre TJ et al. 2010). Existence of a slow-flow/no-reflow state causes persistent inflammation in deep tissue. Animals subsequently develop hyperemia and edema, followed by mechano-hyperalgesia, allodynia, and cold-allodynia lasting for at least 1 month (Coderre et al. 2010). This clinical picture is similar to the clinical signs of those patients afflicted with CRPS-1. Premise 2: Vascular occlusion testing measures microcirculatory dysfunction NIRS measurement of peripheral tissue oxygen saturation (StO2), combined with a reproducible ischemia-reperfusion challenge to induce reactive hyperemia (vascular occlusion testing - VOT), has been described as a valid and reliable method for assessing microcirculatory dysfunction (De Backer et al. 2010). This involves a short period of forearm ischemia by inflating a blood pressure cuff on the upper arm. The blood pressure cuff is then released after approximately 3 minutes and this followed by reperfusion of the forearm. This stimulates the release of endogenous nitric oxide (NO) from the microvascular endothelium (Harel et al 2008). Measurement of this hyperemic response using NIRS has been demonstrated to be a feasible non-invasive method of quantifying microcirculatory function. This technique shares strong correlation with the gold-standard method of strain gauge plethysmography (Harel et al. 2008).

Official Title
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Near-infrared Spectroscopic Measurement of Tissue Oxygen Saturation and the Vascular Occlusion Test in Complex Regional Pain Syndrome

Conditions
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Reflex Sympathetic Dystrophy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Complex regional pain syndrome type 1 (CRPS-I) of one upper extremity. Healthy volunteers. Diagnosis of CRPS-I established for greater than 12 weeks. Exclusion Criteria: Pregnancy Lack of informed consent History of peripheral vascular disease requiring angioplasty or bypass surgery History of systemic vasculitis Current use of vasoactive medications Diabetes Type I and II Presently smoking

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CRPS Type 1<br>Patients with CRPS 1 affecting a single upper limb | |
| Healthy volunteers<br>Volunteers without the diagnosis of CRPS Type 1 | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline tissue oxygen saturation |  | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occlusion slope during vascular occlusion test |  | Day 1 | 
| Reperfusion slope during vascular occlusion test |  | Day 1 | 
| Delta StO2 | Defined as the difference between the maximal tissue oxygenation value after reperfusion and the baseline measurement | Day 1 | 
| Post-obstructive hyperemic response |  | Day 1 | 
| Thenar muscle oxygen consumption |  | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Complex regional pain syndrome, Near Infrared Spectroscopy, Vascular Occlusion Test