Hans Christian Wartenberg

Temperament and character personality profiles and personality disorders in chronic pain patients

Abstract In his psychobiological model of personality, Cloninger developed a novel approach concerning the relationships between psychopathological syndromes and personality. We investigated 207 chronic pain patients (CPPs) and compared them to 105 pain‐free control subjects. Participants were assessed using the Temperament and Character Inventory (TCI), the Structured‐Clinical‐Interview‐II, the Beck Depression Inventory and the Spielberger Anxiety Inventory. The CPPs scored higher on the depression and state anxiety scales and 41% fulfilled the criteria of having at least one personality disorder (PD). We used a covariance analysis to control for depression and state anxiety and found that the CPPs scored higher on the Harm Avoidance Temperament Dimension and lower on the Self‐Directedness and Cooperativeness Character Dimensions. In CPPs, the symptom counts of all PD subtypes were significantly related to low Self‐Directedness and, to a lesser degree, low Cooperativeness. The PD symptoms in Cluster A were related to low Reward Dependence, those in Cluster B were related to high Novelty Seeking and the PD symptoms in Cluster C were related to high Harm Avoidance. In multiple hierarchical regression analyses, controlling for age, gender, depression and state anxiety, TCI scales predicted on average 23% in PD symptom counts. The Self‐Directedness and Cooperativeness personality traits appeared to be significant predictors in determining the presence or absence of a PD by correctly classifying 75.8% of CPPs. The TCI provides further insight into the mechanisms underlying the development of chronic pain. This useful diagnostic instrument helps to economically and validly facilitate the identification of core PD features.

Managing cancer pain and symptoms of outpatients by rotation to sustained-release hydromorphone: a prospective clinical trial

PurposeIn this prospective clinical trial we examined the technique of opioid rotation to oral sustained-release hydromorphone for controlling pain and symptoms in outpatients with cancer pain. MethodsBefore and after rotation, 50 patients were assessed by Numerical Analog Scales [Numerical Rating Scales (NRS)], or as categorical parameters, and analyzed by descriptive and confirmatory statistics (ANOVA, Wilcoxon, χ2). ResultsRotation was successful in 64% of patients experiencing pain (60%), and gastrointestinal (32%) and central (26%) symptoms under oral morphine (38%), transdermal fentanyl (22%), tramadol (20%), oxycodone (12%), or sublingual buprenorphine (8%). NRS of pain (4.1 to 3.2; P=0.015), gastrointestinal symptoms, especially defecation rates (P=0.04), and incidence of insomnia improved after an increase in morphine-equivalent doses from 108.9 to 137.6 mg/d without modifying concomitant analgesics or coanalgesics. ConclusionsSwitching the opioid to oral hydromorphone may be a helpful technique to alleviate pain and several symptoms, but it is still not clear to what extent the underlying mechanisms, such as the technique of rotation itself, better dose adjustment, or using a different opioid have an impact.

Percutaneous fetoscopic laser decompression of congenital high airway obstruction syndrome (CHAOS) from laryngeal atresia via a single trocar--current technical constraints and potential solutions for future interventions

Objective: To alleviate congenital high airway obstruction syndrome (CHAOS) from laryngeal atresia by percutaneous minimally-invasive fetoscopic tracheal decompression using laser. Methods: The procedure was performed via one trocar under general maternofetal anesthesia in a human fetus with CHAOS from laryngeal atresia at 21+6 weeks of gestation. Results: Normalization of the lung-heart size relationship was observed within days after the procedure. The fetus was delivered by ex utero intrapartum treatment (EXIT) in order to perform a tracheotomy at 31+1 weeks of gestation and survived hospital treatment to discharge. Conclusions: Percutaneous minimally-invasive fetoscopic decompression of the fetal trachea via a single trocar is feasible in human fetuses with CHAOS from laryngeal atresia.

Single sodium channels from human ventricular muscle in planar lipid bilayers.

Abstract Sodium channels from human ventricular muscle membrane vesicles were incorporated into planar lipid bilayers and the steady-state behavior of single sodium channels were examined in the presence of batrachotoxin.In symmetrical 500 mM NaCl the averaged single channel conductance was 24.7 ± 1.3 pS and the channel fractional open time was 0.85 ± 0.04. The activation midpoint potential was −99.5 ± 3.1 mV. Extracellular tetrodotoxin blocked the channel with a κ1/2 of 414 nM at 0 mV. In 7 out of 13 experiments subconductance states were observed (9.2 ± 1.2 pS).When sodium chloride concentration was lowered to 100 mM, single channel conductance decreased to 19.0 ± 0.9 pS, steady-state activation shifted by −17.3 ± 5.1 mV, tetrodotoxin sensitivity increased to 324 nM, and sub-conductance states were invariably observed in single channel records (7.9 ± 0.7 pS).In the planar lipid bilayer system the properties of cardiac sodium channels from different species are not very different, but there are significant differences between sodium channels from human heart and from human CNS.

Steady-state properties of sodium channels from healthy and tumorous human brain

This extensive bilayer study of unpurified human brain channels from non-diseased and tumorous human brain involves more than 300 lipid bilayer experiments. Single channel conductances and subconductances, single channel fractional open times, the voltage-dependence of tetrodotoxin (TTX) block and the steady-state activation behavior of four different human brain synaptosomal preparations have been examined. Reproducible values have been obtained for the molecular electrophysiological parameters and their standard deviations, providing a database for future comparisons involving disease or drug-related changes in molecular sodium channel functions. In comparison with sodium channels from other species and under other experimental conditions, the bilayer system proved to be a reliable experimental setting. Despite the very different histology of the tissue probes, there were no significant differences in any of the examined electrophysiological features.

Use of buprenorphine in children with chronic pseudoobstruction syndrome: case series and review of literature.

OBJECTIVES Abdominal pain is the most challenging symptom in chronic intestinal pseudoobstruction (CIPO) syndrome, because of its severity and the limited availability of suitable opioid formulations, especially in pediatric patients with digestive problems. Most of the children with CIPO cannot tolerate oral formulations. CASE REPORTS We present 4 cases of children with CIPO and severe intractable abdominal pain, and report on the use of a recently available form of opioid, transdermal buprenorphine in a dosage of 5 mcg/h. DISCUSSION CIPO and the unique pharmacological profile of buprenorphine are reviewed briefly.

Blocking effects of the anaesthetic etomidate on human brain sodium channels.

Sodium channels from human brain tissue were incorporated into voltage-clamped planar lipid bilayers in presence of batrachotoxin and exposed to increasing concentrations of the intravenous anaesthetic drug etomidate (0.03-1.02 mM). Etomidate interacted with the sodium-conducting pathway of the channel causing a concentration-dependent block of the time-averaged sodium conductance (computer fit of the concentration-response curve: half-maximal blocking concentration, EC50, 0.19 mM; maximal block, block(max), 38%). This block of sodium-conductance resulted from two distinct effects (I) major effect: reduction of the sodium-channel amplitude and (II) minor effect: reduction of the fractional channel open-time. These results were observed at concentrations above clinically-relevant serum concentrations (up to 0.01 mM), suggesting only a limited role for human brain sodium channels in the mechanism of action of etomidate during clinical anaesthesia.

Interactions of ethanol with single human brain sodium channels

Human CNS sodium channels provide a protein model system for our continuing study of anaesthetic drug interactions at the molecular level. The impact of ethanol, an alcohol with general anaesthetic properties, on sodium channel function and their significance for the overall anaesthetic effect was quantified. Sodium channels from human brain cortex tissue were incorporated into voltage-clamped planar lipid bilayers in the presence of batrachotoxin and studied at various ethanol concentrations (0.085 – 0.84 M). Ethanol caused a concentration-dependent and membrane potential independent reduction of the single channel amplitude (major effect) and of the fractional channel open-time (minor effect) with no effect on channel steady-state activation. Severe membrane perturbing effects at the highest ethanol levels terminated the measurements. The weighted computer fit of the concentration-response curve with an estimate of a maximal conductance block of 40% yielded an EC50 of 1.03 M. The EC50 for the 100% maximal theoretical block was calculated to be 3.3 M. These effects occurred at levels far beyond toxic human serum levels (0.1 M; 0.5%). Thus, the human CNS sodium channel is not a main target site for the clinical effects of ethanol and other, more sensitive central receptors are involved in ethanols mechanism of action.

Single sodium channels from human skeletal muscle in planar lipid bilayers: characterization and response to pentobarbital.

PurposeTo investigate the response to general anesthetics of different sodium-channel subtypes, we examined the effects of pentobarbital, a close thiopental analogue, on single sodium channels from human skeletal muscle and compared them to existing data from human brain and human ventricular muscle channels.MethodsSodium channels from a preparation of human skeletal muscle were incorporated into planar lipid bilayers, and the steady-state behavior of single sodium channels and their response to pentobarbital was examined in the presence of batrachotoxin, a sodium-channel activator. Single-channel currents were recorded before and after the addition of pentobarbital (0.34–1.34 mM).ResultsIn symmetrical 500 mM NaCl, human skeletal muscle sodium channels had an averaged single-channel conductance of 21.0 ± 0.6 pS, and the channel fractional open time was 0.96 ± 0.04. The activation midpoint potential was −96.2 ± 1.6 mV. Extracellular tetrodotoxin blocked the channel with a half-maximal concentration (k1/2) of 60 nM at 0 mV. Pentobarbital reduced the time-averaged conductance of single skeletal muscle sodium channels in a concentration-dependent manner (inhibitory concentration 50% [IC50] = 0.66 mM). The steady-state activation was shifted to more hyperpolarized potentials (−16.7 mV at 0.67 mM pentobarbital).ConclusionIn the planar lipid bilayer system, skeletal muscle sodium channels have some electrophysiological properties that are significantly different compared with those of sodium channels from cardiac or from central nervous tissue. In contrast to the control data, these different human sodium channel subtypes showed the same qualitative and quantitative response to the general anesthetic pentobarbital. The implication of these effects for overall anesthesia will depend on the role the individual channels play within their neuronal networks, but suppression of both central nervous system and peripheral sodium channels may add to general anesthetic effects.

No evidence for specific opioid effects on batrachotoxin-modified sodium channels from human brain synaptosomes

Human central nervous system (CNS) sodium channels modified by batrachotoxin and incorporated inter voltage-clamped lipid bilayers, were exposed to various concentrations of the opioid alfentanil (0.2-8.0 mM). Alfentanil caused a concentration-dependent and membrane potential independent reduction of the single channel amplitude and the fractional channel open-time. The weighted computer fit of the dose-response curve yielded a maximal conductance block of 50% with an EC50 of 1.3 mM. These effects occurred at levels beyond clinically relevant human serum/brain levels (0.003 mM) but within the predicted concentration range using the Meyer-Overton (lipid solubility/anaesthetic potency) correlation. Thus, human CNS sodium channels are probably not a main target site for the clinical effects of alfentanil but they provide a model system to estimate the proportion of the lipophilic interactions contributing to its overall effect.