'Cold Case': Vascular dysregulation in the chronic Complex Regional Pain Syndrome

The aim of this thesis was to study the nature of the vascular alterations in patients with cold chronic Complex Regional Pain Syndrome. CRPS usually develops as a disproportionate consequence of trauma and is characterised by spontaneous pain, movement disorders and abnormal regulation of blood flow and sweating. We hypothesised that endothelial dysfunction may in part be responsible for the diminished blood flow in cold chronic CRPS. An improvement on endothelial level would therefore lead to an increased blood flow and a subsequent improvement in pain and activity. In the second chapter we studied the characteristics of 195 patients with potential CRPS that visited our out-patients clinic. We found that a subgroup of patients with a lower temperature in the affected extremity had a longer disease duration and higher pain scores. The results of immunohistochemical staining on skin sections (chapter 3) and the measurement of blister fluids (chapter 4) indicate that endothelial dysfunction may play a role in chronic CRPS. Five female patients were treated with the nitric oxide donor isosorbide dinitrate (ISDN). In this pilot study, described in chapter five, topical application of ISDN improved temperature and pain in most patients. Two randomized placebo-controlled trials were initiated, both including 24 chronic cold CRPS patients. In the first study, which is described in chapter six, ISDN ointment was used by patients with CRPS in one hand. In the second study (chapter 7) the phosphodiesterase inhibitor tadalafil was used to induce vasodilation in patients with CPRS in one foot. Although neither studies produced a significant improvement in temperature asymmetry and blood flow there was a significant reduction of pain in the tadalafil group. We concluded that tadalafil may be a promising new treatment for patients with chronic cold CRPS due to endothelial dysfunction, which deserves further investigation. In chapter 8 we discuss the mechanisms responsible for ischemia and pain in chronic cold CPRS. The diminished blood flow may be caused by either sympathetic dysfunction, hypersensitivity to circulating catecholamines or endothelial dysfunction. Pain in CRPS may be of neuropathic, inflammatory, nociceptive, functional nature or of mixed origin. This origin of the pain should be the basis of the symptomatic therapy. Future research should focus on developing easily applied methods for clinical use to differentiate between central and peripheral blood flow regulation disorders in individual patients

Diagnosing complex regional pain syndrome using an electronic nose, a pilot study

Objective: Complex regional pain syndrome (CRPS)is a complication after surgery or trauma and is characterized by a continuing regional pain in a distal extremity. The pain is disproportionate in severity and duration in relation to the preceding trauma. Currently, the diagnosis is based on the patients’signs and symptoms. There is no objective clinically applicable test available to confirm the diagnosis of CRPS, however this could contribute to a more reliable and valid diagnosis. Since the treatment of CRPS differs from that of other types of pain this could thereby lead to earlier and (more) appropriate treatment and possibly to lower medical costs. The Aeonose™ is a diagnostic test device which detects volatile organic profiles in exhaled air. Exhaled breath analysis using an electronic nose has been successfully applied to differentiate between sick and healthy persons for various indications. This study was a feasibility study in which we investigated whether the Aeonose™ is able to

Effect of radiofrequency denervation on pain intensity among patients with chronic lowback pain the mint randomized clinical trials

IMPORTANCE Radiofrequency denervation is a commonly used treatment for chronic low back pain, but high-quality evidence for its effectiveness is lacking. OBJECTIVE To evaluate the effectiveness of radiofrequency denervation added to a standardized exercise program for patients with chronic low back pain. DESIGN, SETTING, AND PARTICIPANTS Three pragmatic multicenter, nonblinded randomized clinical trials on the effectiveness of minimal interventional treatments for participants with chronic low back pain (Mint study) were conducted in 16 multidisciplinary pain clinics in the Netherlands. Eligible participants were included between January 1, 2013, and October 24, 2014, and had chronic low back pain, a positive diagnostic block at the facet joints (facet joint trial, 251 participants), sacroiliac joints (sacroiliac joint trial, 228 participants), or a combination of facet joints, sacroiliac joints, or intervertebral disks (combination trial, 202 participants) and were unresponsive to conservative care. INTERVENTIONS All participants received a 3-month standardized exercise program and psychological support if needed. Participants in the intervention group received radiofrequency denervation as well. This is usually a 1-Time procedure, but the maximum number of treatments in the trial was 3. MAIN OUTCOMES AND MEASURES The primary outcomewas pain intensity (numeric rating scale, 0-10; whereby 0 indicated no pain and 10 indicated worst pain imaginable) measured 3 months after the intervention. The prespecified minimal clinically important difference was defined as 2 points or more. Final follow-up was at 12 months, ending October 2015. RESULTS Among 681 participants who were randomized (mean age, 52.2 years; 421 wom