[Establishment of an adaptable acute pain model for induction of nociceptive stimuli of defined intensity and duration using thermal stimulation]. / Etablierung eines adaptierbaren Akutschmerzmodells zur Induktion nozizeptiver Stimuli definierter Intensität und Dauer mittels thermischer Reize.

BACKGROUND: In previous years numerous acute pain models to investigate the pathophysiological mechanisms of pain and to validate treatment procedures have been described. Due to the specific questions addressed by different trials standardized protocols are often missing. Therefore, the research results obtained are only comparable or reproducible to a limited extent. The transferability of acquired knowledge to clinical pain is limited by the mostly short test duration of already established models. METHOD: The aim of this study was to establish a standardized protocol for an acute pain model that induces nociceptive thermal stimuli of defined intensity and variable duration using a device for quantitative sensory testing (QST). The greatest possible exclusion of factors influencing pain perception was achieved. In order to reduce the risk of thermal tissue damage a capsaicin cream was applied to the test area, which led to a significant increase in the perceived pain intensity of heat stimuli. RESULTS: From previously performed experiments on thermal pain thresholds and temporal aspects of pain adaptation, the parameters for stimulus lengths and thermode temperatures for a cold and heat pain model could be derived. The acute pain model established here was able to induce significant heat and cold pain stimuli over variable periods of time. An average pain intensity of NRS ≥ 6 was reported by the test participants. Among the 30 subjects no tests were terminated due to intolerance. CONCLUSION: The established acute pain model in this study is characterized by the induction of thermal pain stimuli of defined intensity and variable duration. There is no danger of significant thermal tissue damage and the pain was tolerated by all study participants. The pain model can easily be established using a device for quantitative sensory testing.

["Legal highs" (new psychoactive substances) : What does the anesthesiologist need to know?] / "Legal Highs" (neue psychoaktive Substanzen) : Was muss der Anästhesist wissen?

In recent years, the social media, the press and the internet have reported more about the topic of "legal highs" and new psychoactive substances (NPS). The use of these drugs is accompanied by a serious risk of undesired side effects, intoxication and even death. The often unknown chemical composition, unspecific clinical presentations and lack of quickly available routine diagnostic tests are aggravating factors in this situation. For anesthesiologists, knowledge of this dangerous substance class plays an important role in the field of preclinical treatment, perioperative management and intensive medical care.

[The spinal catheter in aortic surgery : Implications for anesthesia]. / Der Spinalkatheter in der Aortenchirurgie : Implikationen für die Anästhesie.

During surgical repair of aortic pathologies (e.g. dissection, aneurysms), cross-clamping of the aorta or overstenting of critical segmental arteries can lead to ischemia- and edema-related spinal cord damage with subsequent paraplegia. By regulating cerebrospinal fluid pressure, the spinal catheter is an effective method for prophylaxis and treatment of spinal cord ischemia. Due to the high complication rate of the spinal catheter a detailed risk-benefit assessment is obligatory: besides cerebrospinal fluid leakage, postpuncture headaches and local infections, feared complications, such as intracranial bleeding, meningitis and neuraxial hematomas can also occur, sometimes with a significant latent period after termination of the procedure. Adequate training of personnel in the perioperative handling of spinal catheters and meticulous adherence to drainage parameters are important components for increasing procedural safety. This is particularly true since the clinical aspects of catheter-associated complications only slightly differ from that of ischemic spinal cord injury.

[Efficacy of biofeedback in patients with chronic low back pain : Impact on pain intensity, psychological factors and stress markers]. / Effektivität von Biofeedback bei Patienten mit chronischem Rückenschmerz : Einfluss auf Schmerz, psychologische Faktoren und Stressmarker.

BACKGROUND: The treatment of patients with chronic pain should be carried out in interdisciplinary multimodal pain programs of which relaxation methods represent an integral part. The German disease management guidelines (NDGM) on nonspecific low back pain currently do not recommend biofeedback as a relaxation technique for chronic low back pain due to inadequate data. Furthermore, health insurances do not cover the costs of this treatment. METHODS: The efficacy of a 2-week biofeedback treatment was evaluated in a study of 10 patients with chronic nonspecific low back pain and 10 healthy, age and gender-matched subjects. The parameters "well-being", "depressive mood" and "pain-related disability" were assessed based on three psychometric tests (KAB, ADS and PDI). The pain intensity was measured using a numeric rating scale (NRS) and biofeedback measurement parameters themselves as well as stress markers in blood (noradrenaline, cortisol and MMP-2) were also measured. RESULTS: The relaxation response was demonstrated by the biofeedback-parameters. The treatment led to an improvement in well-being, depressive mood and pain-related disability. These results correlated with a reduction of noradrenaline and MMP-2 blood levels, whereas cortisol concentrations showed no change. CONCLUSION: Biofeedback relaxation is a suitable method in the treatment of chronic non-specific low back pain. Its use in interdisciplinary multimodal pain programs should be encouraged.

[Differential indications of opioids in pain therapy]. / Differenzialindikation von Opioiden in der Schmerztherapie.

Due to their strong analgesic potency opioids are highly effective in the therapy of acute and particularly cancer-induced chronic pain; however, the individual opioids differ considerably with respect to their pharmacokinetic and physicochemical properties and may therefore not be equally applicable for every patient. Caution should be taken especially in patients with impaired organ function. Furthermore, the metabolism of opioids leads to active or inactive metabolites. This process can be substantially influenced by genetic polymorphisms or drug interactions. Knowledge of all these factors for individual opioids, which influence the efficacy and side effects, is therefore crucial. In this review the pharmacology, clinical applications, metabolism and genetic factors of the most important opioids used for pain management are discussed.

[Multimodal pain therapy. Current situation]. / Multimodale Schmerztherapie. Eine Standortbestimmung.

A multidisciplinary approach for the management of patients with chronic pain is now well-established in many countries, especially in situations involving a complex disease process in the sense of a biopsychosocial model. Both the efficacy and cost-effectiveness of multidisciplinary pain treatment programs and their superiority compared to unimodal therapy has been documented in a number of studies, reviews and meta-analyses, in particular for patients suffering from chronic low back pain. Nevertheless, there are still major shortcomings concerning the definition of multimodal and multidisciplinary treatment and the quality of structures and processes, compared for example to the standards defined by the German Pain Society (Deutsche Schmerzgesellschaft). Furthermore, there is still no consensus on specific therapeutic approaches, the differentiation between responders and non-responders as well as on the tools required for measurement. All these questions will have to be answered by concerted efforts in a multicenter setting.

[Quality of postoperative pain therapy: evaluation of an established anesthesiology acute pain service]. / Qualität der postoperativen Schmerztherapie : Evaluation eines etablierten anästhesiologischen Akutschmerzdiensts.

BACKGROUND: Despite well-designed concepts of perioperative pain management, recent studies have revealed that a large number of patients still suffer from unacceptable pain after surgery. The purpose of this prospective evaluation was to critically analyze postoperative pain treatment provided by a routinely established, DIN certified acute pain service (APS) at the University Hospital Großhadern in Munich. MATERIALS AND METHODS: A total of 1,000 consecutive patients received one of the following analgesic procedures: continuous epidural analgesia (EA, n = 401), continuous and patient-controlled epidural analgesia (PCEA, n = 305), intravenous patient-controlled analgesia with opioids (PCA, n = 169) or continuous peripheral nerve block (CPNB, n = 125). For EA and PCEA, ropivacaine 0.2 % and sufentanil 0.24 µg/ml were administered while peripheral regional analgesia was performed with infusion of ropivacaine 0.2 % only. Patients with PCEA were allowed a 3 mg bolus once per hour on demand. Standardized intravenous PCA was performed with piritramide 2.5 mg/ml, a bolus of 2.5 mg, a lock-out time of 15 min, a maximum of 25 mg/4 h and no background infusion. During the daily visits the APS assessed pain intensity at rest and during movement on a numerical rating scale from 0 (no pain) to 10 (maximum pain), acceptance of pain, satisfaction with the analgesic procedure, demand of additional non-opioid analgesics, the need for optimization including bolus applications and changes of the infusion rate or retraction of the epidural catheter. The duration of the procedures, side effects and complications were documented. The catheter insertion sites were inspected daily for redness and tenderness on palpation. RESULTS: In general, epidural and peripheral regional analgesic techniques were superior in terms of postoperative analgesia to intravenous opioid PCA and were associated with fewer side effects, such as sedation, nausea, vomiting, obstipation and sensorimotor deficits. A subgroup analysis revealed that in major upper abdominal surgery, EA provided significantly better analgesia at rest and during movement than PCA. In lower abdominal surgery PCEA induced significantly better analgesia than both PCA and EA, especially during movement. Patient satisfaction was generally high and was best with PCEA (95 %) followed by CPNB (94 %), EA (91 %) and PCA (88 %). On the first postoperative day analgesic procedures had to be optimized (e.g. by bolus administration, retraction of catheters or changes to standardized PCA) in 23 % of EA patients, 10 % of PCEA patients, 6 % of PCA patients and 12 % of CPNB patients. Major complications, such as neuraxial hematoma, infections or respiratory depression were not observed. CONCLUSIONS: As described in many prospective studies, this evaluation revealed that for postoperative pain control, regional anesthesia is superior to intravenous patient-controlled analgesia with strong opioids in terms of analgesia and side effects. In the setting of a well-organized acute pain service with frequent education and training of all members involved, postoperative pain management is safe and effective. However, regular re-evaluation of the defined and certified procedures is necessary.

[Patients with chronic pain syndromes. Impact of an individual outpatient therapy program on pain and health-related quality of life]. / Patienten mit chronischen Schmerzsyndromen. Einfluss einer ambulanten individuellen Therapie auf Schmerzen und gesundheitsbezogene Lebensqualität.

BACKGROUND: The study was performed to reveal the effect of an individualized personal outpatient therapy program, based on a multidisciplinary assessment, on pain and health-related quality of life in patients with chronic pain. METHODS: Fifty patients were prospectively evaluated before and 3 months after establishment of an individualized outpatient therapy program. Health-related quality of life, pain and pain-related disability, depression and motivation to adopt self-management of chronic pain were assessed. Therapy adherence was tested with a structured interview. RESULTS: Only marginal improvements were observed in terms of pain and health-related quality of life. Therapy adherence varied between the different therapies. CONCLUSIONS: An individualized personal outpatient therapy program has only marginal effects on pain and health-related quality of life in patients with chronic pain.

Lack of interaction of endocannabinoids and 5-HT(3) neurotransmission in associative fear circuits of the amygdala: evidence from electrophysiological and behavioural experiments.

Both the serotonergic and the endocannabinoid system play a major role in mediating fear and anxiety. In the basolateral amygdala (BLA) it has been shown that the cannabinoid receptor 1 (CB1) is highly co-expressed with 5-HT3 receptors on GABAergic interneurons suggesting that 5-HT3 receptor activity modulates CB1-mediated effects on inhibitory synaptic transmission. In the present study, we investigated the possible interactions of CB1 and 5-HT3-mediated neuronal processes in the BLA using electrophysiological and behavioural approaches. Whole-cell patch-clamp recordings were performed in coronal brain slices of mice. Electric stimuli were delivered to the lateral amygdala to evoke GABAA receptor-mediated inhibitory postsynaptic currents (GABAA-eIPSCs) in the BLA. The induction of LTDi, a CB1-mediated depression of inhibitory synaptic transmission, was neither affected by the 5-HT3 antagonists ondansetron (OND; 20 µM) and tropisetron (Trop; 50 nM) nor by the 5-HT3 agonists SR57227A (10 µM). In auditory fear conditioning tests, mice treated with SR57227A (3.0mg/kg i.p.) showed sustained freezing, whereas treatment with Trop (1.0 mg/kg i.p.) decreased the expression of conditioned fear. These effects were overruled by the CB1 antagonist rimonabant (RIM; 3.0 mg/kg), which caused increased freezing with or without co-treatment with Trop. In summary, these experiments do not support a functional interaction between CB1 and 5-HT3 receptors at the level of GABA neurotransmission in the BLA nor in terms of fear regulation.

[Endogenous cannabinoid system. Effect on neuronal plasticity and pain memory]. / Endogenes Cannabinoidsystem. Einfluss auf neuronale Plastizität und Schmerzgedächtnis.

AIM: The aim of this study was to evaluate the role of the endogenous cannabinoid system in controlling neuroplasticity. METHODS: The pain threshold for electrical stimuli was determined in transgenic mice lacking the cannabinoid receptor type 1 (CB1(-/-)) and in the corresponding respective wild-type animals. Electrophysiological experiments were performed in prepared brain slices to test the effect of endogenous and exogenous cannabinoids on synaptic transmission and long-term potentiation (LTP) in the amygdala. RESULTS: The pain threshold was nearly identical in both groups for the first pain induction; however, with repeated pain induction it decreased to a significantly greater extent in the CB1(-/-) mice than in the wild-type animals. Synoptic transmission and the inducibility of LTP were not influenced by the acute pharmacological blockade of CB1 receptors, but inhibited by the CB1 agonist WIN55,212-2. CONCLUSION: The endogenous cannabinoid system is involved in the control of neuroplasticity as part of pain processing . Cannabinoids prevent the formation of LTP in the amygdala via activation of CB1 receptors. Synoptic transmission and the inducibility of LTP were not influenced by the acute pharmacological blockade of CB1 receptors, but inhibited by the CB1 agonist Win55,212-2.

Perioperative pain management in patients undergoing thoracic surgery.

Adequate perioperative pain management has become an important part of thoracic anaesthesia. In the past few years, many trials have been performed to evaluate the efficacy of various analgesic regimens. This review summarizes the most frequently used analgesic techniques, with a particular emphasis on the results of studies and innovative ideas published between August 1999 and August 2000.

[What do we know about the state of chronic pain?]. / Was wissen wir über die Chronifizierung von Schmerz?

Chronic pain syndromes are characterized by altered neuronal excitability in the pain matrix. The ability to rapidly acquire and store memory of aversive events is one of the basic principles of nervous systems throughout the animal kingdom. These neuroplastic changes take place e. g. in the spinal cord, in thalamic nuclei and cortical and subcortical (limbic) areas integrating pain threshold, intensity and affective components. Chronic inflammation or injury of peripheral nerves evokes the reorganisation of cortical sensory maps. Neurons conveying nociceptive information are controlled by various sets of inhibitory interneurons. The discharge activity of these interneurons counteracts long-term changes in the pain matrix following nociceptor activation, i. e. it prevents the transition of acute pain signaling to chronic pain states. Our most recent research suggests that pain states may be sensitive to novel families of agents and therapeutic measures not predicted by traditional preclinical pain models as well as human pain states. The endogenous cannabinoid system plays a central role in the extinction of aversive memories. We propose that endocannabinoids facilitate extinction of aversive memories via their selective inhibitory effects on GABAergic networks in the amygdala.

[Diagnostic criteria and new classification of the cervical spine syndrome]. / Diagnostische Kriterien und neue Klassifikation des Halswirbelsäulensyndroms.

OBJECTIVES: Pain and functional disorders of the neck are widely diagnosed as "cervical spine syndrome". As this diagnosis is not able to sufficiently specify the different symptoms, a new classification with five pain syndromes, created empirically, was developed. The aim of this study is to evaluate the predictive values of the diagnostic criteria respectively clinical findings of patients diagnosed with cervical spine syndrome. METHODS: Within the two year time frame of the study all patients diagnosed with "cervical spine syndrome", which presented themselves at the clinic, were included. The statistic analysis was performed in multiple steps: univariate analyses, bivariate variable screening and the use of the logistic regression model. RESULTS: Within two years 653 patients previously diagnosed as suffering from cervical spine syndrome presented at the clinic; 332 of them were included in the study. According to the diagnostic criteria they were attached to one of the five pain syndromes. The statistical analysis showed in 17 of 35 evaluated diagnostic criteria a significant association to one of the five subgroups of the cervical spine syndrome. CONCLUSION: The statistical analyses revealed significant associations between diagnostic criteria which were assessed by clinical examination and the five subgroups of the cervical spine syndrome. The identified predictors represent the typical syndrome-associated diagnostic criteria of a certain syndrome-subgroup.

[Monitoring blood coagulation in larger liver operations]. / Monitoring der Blutgerinnung bei grossen Leberoperationen.

Bleeding is causally related to about 50% of postoperative deaths following liver resection. Main factors contributing to increased perioperative bleeding in liver surgery include surgical trauma, reduced activity of clotting factors and inhibitors due to impaired hepatic synthesis, low platelet count and poor platelet function as well as impaired clearance of activated clotting factors by the reticuloendothelial system of the liver (Kupffer cells). Hemostasis may be further impaired by transfusion of blood components, since citrate added for conservation is not adequately metabolized by the failing liver. Surgical bleeding leads to a loss of pro- and anticoagulatory factors as well as to activation of coagulation. Finally, hyperfibrinolysis induced by release of tissue plasminogen activator (t-PA, primary hyperfibrinolysis) and disseminated coagulation (secondary hyperfibrinolysis) contribute to increased bleeding. Therefore early diagnosis and treatment of coagulation disorders is of paramount importance during liver surgery. Screening parameters of hemostasis and fibrinolysis should be available on a 24-hour basis in centers performing liver surgery. Screening for disorders of secondary hemostasis includes evaluation of prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration and the activity of the most important inhibitor, antithrombin III (AT III). Thrombelastography is the leading method for diagnosis of hyperfibrinolysis, which can also be assessed by determination of D-dimer, fibrinogen and fibrin degradation products. Evaluation of primary hemostasis is frequently restricted to platelet count, which is only a rough parameter. In contrast, measurement of in vitro bleeding time and volume enables repeated quantification of platelet function in patients with impaired hemostasis.

[The effects of aprotinin. Blood loss and coagulation parameters in orthotopic liver transplantation: A clinical-experimental, prospective and randomized double-blind study]. / Die Wirkung von Aprotinin. Blutverlust und Gerinnungsparameter bei orthotoper Lebertransplantation: Eine klinisch-experimentelle, prospektive und randomisierte Doppelblindstudie.

The effect of aprotinin (2,000,000 IU as a bolus +500,000 JU/h until the end of the operation) on transfusion requirements and coagulation parameters in orthotopic liver transplantation (study group: n = 9; placebo group: n = 9) was investigated in a randomised, double-blind study. Coagulation parameters were monitored intraoperatively using a mobile laboratory. In contrast to the published results, no effect on transfusion requirements could be demonstrated. However, aprotinin showed a positive effect on some coagulation parameters in the reperfusion phase. The mechanism appeared to be inhibition of the contact activation of the intrinsic system with less thrombin generation in the study group.

[Continuous peridural analgesia vs patient - controlled intravenous analgesia for pain therapy after thoracotomy]. / Kontinuierliche Periduralanalgesie versus patientenkontrollierte intravenöse Analgesie.Schmerztherapie nach Thorakotomien.

OBJECTIVES: Continuous epidural analgesia (EA) and patient-controlled intravenous analgesia (PCA) are widely used for postoperative pain control. Studies indicate that both analgesic regimens provide good analgesia after major surgery. However, because of the following reasons it is still unclear whether one of the two modes of application is superior. First, there are conflicting data regarding the differences in pain relief and drug use between epidural and intravenous administration of opioids. Second, in many studies epidural analgesia is performed by a combination of local anaesthetics and opioids. Third, reduced morbidity was observed only in some of the studies, in which epidural analgesia provided better pain relief than systemic opioid supply. Despite these conflicting results, EA with local anaesthetics and fentanyl as well as PCA with piritramid, a highly potent mu-agonist, are routinely used in Germany. The purpose of this study was to compare these two treatments for analgesic efficacy, pulmonary function, incidence of side effects and complications in patients undergoing thoracotomy. METHODS: In this prospective randomized trial 50 patients were included. For postoperative pain control 25 patients (EA group) received thoracic epidural infusion of local anaesthetics (bupivacaine 0.125% or ropivacaine 0,2%) and fentanyl 4,5 microg/ml with a flow rate of 4-10 ml/h. 25 patients received intravenous PCA with piritramid (bolus 2, 5 mg, lock out 15 minutes, maximum of 25 mg/4 h, no background infusion). RESULTS: Analgesia at rest and while coughing, as evaluated by visual analogue scale, was significantly better in the EA group. EA also resulted in superior values of pulmonary function tests, general condition and a lower incidence of sedation and nausea. In contrast, patients with EA reported distinctly more pruritus than patients with PCA. Duration of hospital stay was shorter in the EA group, but this difference did not reach statistical significance. There was one atelectasis in the EA group. No major complications related to EA or PCA were observed. CONCLUSION: In this study EA with local anaesthetics and fentanyl provided superior postoperative pain control and a lower incidence of sedation and nausea compared to intravenous PCA with piritramid, but there was no superiority as to pulmonary complications and duration of hospital stay.

Alpha2-adrenoreceptor activation inhibits LTP and LTD in the basolateral amygdala: involvement of Gi/o-protein-mediated modulation of Ca2+-channels and inwardly rectifying K+-channels in LTD.

Activation of adrenoreceptors modulates synaptic transmission in the basolateral amygdala. Here, we investigated the effects of alpha2-adrenoreceptor activation on long-term depression and long-term potentiation in an in vitro slice preparation of the mouse basolateral amygdala. Field potentials and excitatory postsynaptic currents were evoked in the basolateral amygdala by stimulating the lateral amygdala. Norepinephrine (20 micro m) reduced synaptic transmission and completely blocked the induction of long-term potentiation and long-term depression. The alpha2-adrenoreceptor antagonist yohimbine (2 micro m) reversed this effect. The alpha2-adrenoreceptor agonist clonidine (10 micro m) mimicked the effects of norepinephrine. The Gi/o-protein inhibitor pertussis toxin (5 micro g/mL) reversed the effect of clonidine. Long-term depression was blocked in the presence of omega-conotoxin GVIA, but not omega-agatoxin IVA. Clonidine inhibited voltage-activated Ca2+ currents mediated via N- or P/Q-type Ca2+-channels. The inhibitory action of clonidine on long-term depression was reversed when inwardly rectifying K+-channels were blocked by Ba2+ (300 micro m). The present data suggest that alpha2-adrenoreceptor activation impairs the induction of long-term depression in the basolateral amygdala by a Gi/o-protein-mediated inhibition of presynaptic N-type Ca2+-channels and activation of inwardly-rectifying K+-channels.