Recovery of mechanical detection thresholds after direct digital nerve repair versus conduit implantation.

The purpose of this study was to assess sensory and functional nerve recovery after digital nerve injury in patients with an end-to-end suture (S) or with implantation of a collagen conduit (C) to bridge a nerve gap. Fifteen S and 11 C with a follow-up of 6-36 months and 28 healthy control participants were enrolled. Methods of assessments were quantitative sensory testing, the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH), range of motion and the painDetect questionnaire. After both procedures, sensory profiles showed largely recovered function of C and Aδ fibres but severe loss of Aß-fibre function leading to increased mechanical detection thresholds. There was only minimal allodynia. Severe pain was absent. Patients with conduits reported more functional impairment, especially in work performance, which correlated with the assessed loss of Aß-fibre function. LEVEL OF EVIDENCE: III.

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.

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.

Presence of hyperalgesia predicts analgesic efficacy of topically applied capsaicin 8% in patients with peripheral neuropathic pain.

BACKGROUND: Topical high-dose capsaicin acting on TRPV1 receptors and inducing an intraepidermal decrease in the small nerve fibre count is effective in treating neuropathic pain (NP). Sensory changes after capsaicin application, their correlation with pain relief and their role as possible predictors of response have been insufficiently analysed. We hypothesized a positive correlation between pain relief and increase in the warmth detection threshold (WDT), indicating loss of C-fibre function, and higher response rates in patients with preserved C-fibre function or heat hyperalgesia before application. METHODS: Quantitative Sensory Testing (DFNS protocol) was conducted in 20 unilaterally treated patients with peripheral NP (peripheral nerve injury: n = 14, polyneuropathy: n = 4, postherpetic neuralgia: n = 2) before and 2, 4, 6 and 8 weeks after application of capsaicin (8%) in this open-label study. Response was defined as ≥30% or ≥2 (Numeric Rating Scale: 0-10) decrease of current pain at any follow-up compared to baseline. RESULTS: In all patients, WDT significantly increased 8 weeks after capsaicin application, but did not correlate with pain relief in responders (n = 10, r = 0.179, p = 0.141). Before treatment, responders showed significantly higher z-values for the cold (CPT, +0.7 ± 1.1 vs. -0.4 ± 0.9) and mechanical pain threshold (MPT; 0.7 ± 2.5 vs. -1.2 ± 1.3), but did not differ from non-responders regarding WDT or heat pain threshold. A sum of the z-values for CPT and MPT >0.8 before treatment identified responders with 100% specificity and 70% sensitivity. CONCLUSIONS: Efficacy of capsaicin does not correlate with the induced loss of function of small fibres, measured by QST. Presence of cold and pinprick hyperalgesia seems to be predictive of response to capsaicin (8%).

Immunosuppression enhances atherogenicity of lipid profile after transplantation.

BACKGROUND: Patients after renal transplantation exhibit high cardiovascular morbidity and mortality because of the accumulation of cardiovascular risk factors such as hypertension or dyslipidemia. To elucidate the influence of immunosuppressive therapy on hyperlipidemia, we studied serum lipids and lipoproteins in renal transplant patients who received prednisone and either azathioprine or cyclosporine or triple immunosuppressive therapy. METHODS: Serum lipids and lipoprotein levels were measured in 216 renal transplant patients (81 female and 135 male) with stable graft function of 4.8 +/- 2.3 years (range six months to eight years) after transplantation. Patients were divided into three groups according to one of the following immunosuppressive regimens: (a) prednisone and azathioprine, (b) prednisone and cyclosporine, or (c) prednisone, azathioprine, and cyclosporine. Healthy, age- and sex-matched subjects served as controls. In addition to measurement of total serum lipids, lipoproteins were isolated by preparative ultracentrifugation, and lipids were determined in very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) density classes. RESULTS: Total serum triglycerides, VLDL, and LDL triglycerides, as well as VLDL cholesterol were elevated in all renal transplant patients, but elevation was pronounced in female patients. In contrast to total serum cholesterol, which was significantly increased in only female patients, elevation of LDL-triglyceride/apo B ratio was more marked in male patients. Patients in group A exhibited only mild hypertriglyceridemia, whereas triglyceride enrichment in VLDL and LDL was more distinct in group B and was most pronounced in patients of group C. Furthermore, hypertriglyceridemia increased with the dose of administered prednisone. CONCLUSIONS: Immunosuppressive therapy in renal transplant patients leads to accumulation of triglyceride-enriched VLDL and LDL. Triglyceride enrichment in LDL indicates the accumulation of small, dense LDLs, which are known to bear enhanced atherosclerotic risk. This study provides data that underline the use of individually adjusted immunosuppressive therapy and steroid-sparing protocols in renal transplant patients to improve their atherogenic lipoprotein profile.

"Small volume resuscitation" as treatment of cerebral blood flow disturbances and increased ICP in trauma and ischemia.

"Small volume resuscitation" (SVR) is a promising concept for the treatment of shock and trauma patients. SVR utilizes the fast infusion of a small volume of hypertonic saline to mobilize intraendothelial and parenchymal water to expand and restitute intravascular volume. Therefore it seems warranted to also consider SVR for the treatment of disturbances of the cerebral circulation and of increased intracranial pressure (ICP). The current study uses a rabbit model of global cerebral ischemia combined with mild hemorrhage to test SVR. Somatosensory evoked potentials (SEPs) serve as a short-term outcome parameter. The data demonstrate a beneficial effect treatment with hypertonic/hyperoncotic saline/hydroxyethylstarch as compared to volume replacement with starch or blood.