Unimpaired endogenous pain inhibition in the early phase of complex regional pain syndrome.

BACKGROUND: The complex regional pain syndrome (CRPS) is characterized by distal generalisation of pain beyond the initial trauma. This might be the result of impaired endogenous pain inhibition. METHOD: We compared Conditioned Pain Modulation (CPM) between patients with CRPS (n = 24; pain: 4.5 ± 2.2, NRS 0-10; disease duration <1 year), neuralgia (n = 17; pain: 5.5 ± 1.1) and healthy subjects (n = 23) and its correlation with loss and gain of function as assessed by Quantitative Sensory Testing (QST). CPM was assessed with heat as test stimulus (TS) and cold water as conditioning stimulus (CS). The early CPM-effect was calculated as difference between heat pain during and before conditioning, the late CPM-effect, 5 minutes after and before conditioning, respectively. RESULTS: Heat pain decreased comparably after CS in all groups, resulting in a significant CPM-effect (healthy: -12.5 ± 12.4, NRS 0-100; CRPS: -14.7 ± 15.7; neuralgia: -7.9 ± 9.8; p < 0.001). When compared to healthy subjects, heat pain declined significantly steeper in CRPS patients (healthy: -2.0 ± 5.5, NRS 0-100/10 s; CRPS: -6.3 ± 8.1; p < 0.05). Only CRPS patients demonstrated a late CPM effect (-6.0 ± 9.0, p < 0.005). Neither spontaneous pain nor any QST parameter correlated with CPM, with the exception of a decreased cold pain threshold, which correlated with an enhanced CPM in CRPS patients only (r = -0.456, p < 0.05). CONCLUSION: An impairment of endogenous pain inhibition does not explain the extent of pain in the early stage of CRPS or in neuralgia. The unexpectedly high CPM in CRPS patients might result from activation of the intact descending pathways in response to central sensitization, as cold hyperalgesia correlated with the CPM-effect. SIGNIFICANCE: Conditioned pain modulation (CPM) is not impaired in the early phase of complex regional pain syndrome (CRPS) and neuralgia. Only in CRPS higher CPM was associated with lower cold pain thresholds.

Remote ischaemic conditioning decreases blood flow and improves oxygen extraction in patients with early complex regional pain syndrome.

BACKGROUND: Remote ischaemic conditioning (RIC) is the cyclic application of non-damaging ischaemia leading to an increased tissue perfusion, among others triggered by NO (monoxide). Complex regional pain syndrome (CRPS) is known to have vascular alterations such as increased blood shunting and decreased NO blood-levels, which in turn lead to decreased tissue perfusion. We therefore hypothesized that RIC could improve tissue perfusion in CRPS. METHOD: In this proof-of-concept study, RIC was applied in the following groups: in 21 patients with early CRPS with a clinical history less than a year, in 20 age/sex-matched controls and in 12 patients with unilateral nerve lesions via a tourniquet on the unaffected/non-dominant upper limb. Blood flow and tissue oxygen saturation (StO2 ) were assessed before, during and after RIC via laser Doppler and tissue spectroscopy on the affected extremity. The oxygen extraction fraction was calculated. RESULTS: After RIC, blood flow declined in CRPS (p < 0.01). StO2 decreased in CRPS and healthy controls (p < 0.01). Only in CRPS, the oxygen extraction fraction correlated negatively with the decreasing blood flow (p < 0.05). CONCLUSION: Contrary to our expectations, RIC induced a decrease of blood flow in CRPS, which led to a revised hypothesis: the decrease of blood flow might be due to an anti-inflammatory effect that attenuates vascular disturbances and reduces blood shunting, thus improving oxygen extraction. Further studies could determine whether a repeated application of RIC leads to a reduced hypoxia in chronic CRPS. SIGNIFICANCE: Remote ischaemic conditioning leads to a decrease of blood flow. This decrease inversely correlates with the oxygen extraction in patients with CRPS.