Near-infrared Spectroscopic Measurement in Complex Regional Pain Syndrome
Condition: Reflex Sympathetic Dystrophy
MeSH terms: Complex Regional Pain Syndromes; Reflex Sympathetic Dystrophy
Study type: Observational

Summary: 
      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: 
      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).
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with CRPS Type 1 will be selected from a tertiary care chronic pain clinic.
        Healthy volunteers will be selected from a community sample
      
Keywords: Complex regional pain syndrome; Near Infrared Spectroscopy; Vascular Occlusion Test