Esben Bolvig Mark

The effects of analgesics on central processing of tonic pain: A cross-over placebo controlled study

Introduction: Opioids and antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) are recognized as analgesics to treat moderate to severe pain, but the central mechanisms underlying their analgesia remain unclear. This study investigated how brain activity at rest and exposed to tonic pain is modified by oxycodone (opioid) and venlafaxine (SNRI). Methods: Twenty healthy males were included in this randomized, cross‐over, double‐blinded study. 61‐channel electroencephalogram (EEG) was recorded before and after five days of treatment with placebo, oxycodone (10 mg extended release b.i.d) or venlafaxine (37.5 mg extended release b.i.d) at rest and during tonic pain (hand immersed in 2 °C water for 80 s). Subjective pain and unpleasantness scores of tonic pain were recorded. Spectral analysis and sLORETA source localization were done in delta (1–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), beta1 (12–18 Hz) and beta2 (18–32 Hz) frequency bands. Results: Oxycodone decreased pain and unpleasantness scores (P < 0.05), whereas venlafaxine decreased the pain scores (P < 0.05). None of the treatments changed the spectral indices or brain sources underlying resting EEG. Venlafaxine decreased spectral indices in alpha band of the EEG to tonic pain, whereas oxycodone decreased the spectral indices and brain source activity in delta and theta frequency bands (all P < 0.05). The brain source activity predominantly decreased in the insula and inferior frontal gyrus. Conclusion: The decrease of activity within insula and inferior frontal gyrus is likely involved in pain inhibition due to oxycodone treatment, whereas the decrease in alpha activity is likely involved in pain inhibition due to venlafaxine treatment. HighlightsOxycodone decreased delta and theta spectral indices of EEG to tonic pain.Oxycodone decreased the brain activity underlying delta and theta EEG bands.Venlafaxine decreased alpha spectral indices of EEG to tonic pain.Brain activity underlying lower EEG frequencies is likely important in opioid analgesia.Alpha EEG activity is likely important in SNRI analgesia.

Assessment of colorectal length using the electromagnetic capsule tracking system: a comparative validation study in healthy subjects

We aimed to determine colorectal length with the 3D‐Transit system by describing a ‘centreline’ of capsule movement and comparing it with known anatomy, as determined by magnetic resonance imaging (MRI). Further, we aimed to test the day‐to‐day variation of colorectal length assessed with the system.

Reliability and validity of the new VikingSlice software for computed tomography body composition analysis

Background/objectivesBody composition assessment by computed tomography (CT) is increasingly used for diagnostic and prognostic purposes in various patient groups. This study aimed to compare the reliability and validity of a newly in-house developed segmentation software VikingSlice against a commercial software (SliceOMatic) for quantification of adipose tissue and skeletal muscle cross-sectional areas (CSA).Subjects/methodsFifty abdominal CT sets from chronic pancreatitis patients were analyzed (mean age 49, range 27–84 years; 38 males). Soft tissue CSAs at level of 4th lumbar vertebra were assessed by measuring standard Hounsfield unit threshold definitions with both softwares. Analysis with VikingSlice included automatic segmentation of interested region with subsequent manual corrections. Analysis with SliceOMatic included manual segmentation of each area. Same investigator measured CSAs using both programs. Inter-observer reliability of CSAs measurements with VikingSlice were assessed by comparing results from two independent investigators. Measurements were compared using the intra-class correlation coefficient (ICC), coefficient of variation (CV), Jaccard index and Bland–Altman analyses.ResultsThe inter-observer reliability of VikingSlice was excellent (CV 3.4–15.4%, ICC 0.979–0.999, Jaccard index 0.68–0.98). Validity was high (CV 1.6–10.2%, ICC 0.950–0.997) for measurements by SliceOmatic and VikingSlice. The findings were supported in the Bland–Altman plots. The reliability study had small average differences with means of soft tissue compartments in range −2.29 cm2 to 1.56 cm2; average differences between both softwares were −1.28 cm2 to 0.31 cm2.ConclusionsThe in-house developed software VikingSlice was fast and showed good reliability that is comparable with commercial software in its utility to estimate adipose tissue and skeletal muscle CSAs.

MRI assessed pancreatic morphology and exocrine function are associated with disease burden in chronic pancreatitis

Background and aim The aim of this study was to explore the association between morphological and functional secretin-stimulated MRI parameters with hospitalization, quality of life (QOL), and pain in patients with chronic pancreatitis (CP). Patients and methods This prospective cohort study included 82 patients with CP. Data were obtained from clinical information, QOL, and pain as assessed by questionnaires (The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and modified Brief Pain Inventory short form). Secretin-stimulated MRI morphological parameters included pancreatic gland volume, main pancreatic duct diameter, the modified Cambridge Classification of Duct Abnormality, apparent diffusion coefficient, fat signal fraction, and the pancreatic secretion volume as a functional parameter. The primary outcomes were time to first hospitalization related to the CP, as well as annual hospitalization frequency and duration. The secondary outcomes were pain severity, QOL, and pain interference scores. Results A main pancreatic duct diameter below 5 mm was associated with reduced time to first hospitalization (hazard ratio=2.06; 95% confidence interval: 1.02–4.17; P=0.043). Pancreatic secretion volume was correlated with QOL (r=0.31; P=0.0072) and pain interference score (r=−0.27; P=0.032), and fecal elastase was also correlated with QOL (r=0.28; P=0.017). However, functional and morphological findings were not related to pain intensity. Conclusion Advanced pancreatic imaging techniques may be a highly sensitive tool for prognostication and monitoring of disease activity and its consequences.

Colorectal Transit and Volume During Treatment With Prolonged-release Oxycodone/Naloxone Versus Oxycodone Plus Macrogol 3350

Background/Aims Opioid-induced constipation (OIC) is the most common gastrointestinal (GI) side effect to opioid treatment. Opioid receptor antagonists against OIC have been introduced, but their efficacy has not been directly compared to conventional laxatives. Our aim was to compare symptoms and objective parameters of gut function in an experimental model of OIC during treatment with the opioid antagonist naloxone and oxycodone in prolonged-release (PR) formulation versus oxycodone plus macrogol 3350. Methods In this randomized, double-blind, crossover trial 20 healthy men received a 5-day treatment of combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350. Regional GI transit times and segmental colorectal transit were assessed with the Motilis 3D-Transit electromagnetic capsule system. Colorectal volumes were determined by MRI. OIC symptoms were assessed with validated questionnaires, along with stool frequency and consistency. Results Total colorectal volume did not change after 5 days’ treatment with PR oxycodone/naloxone (941 vs 1036 mL; P = 0.091), but increased significantly after PR oxycodone plus macrogol treatment (912 vs 1123 mL; P < 0.001). Neither regional GI transit times nor segmental colorectal transit differed between the treatments (all P > 0.05). The Patient Assessment of Constipation Symptom Questionnaire abdominal symptoms score was lower during PR oxycodone/naloxone compared to PR oxycodone plus macrogol (0.2 vs 3.2; P = 0.002). Stool frequency was lower during PR oxycodone/naloxone compared to PR oxycodone plus macrogol (4.2 vs 5.4; P = 0.035). Conclusions PR oxycodone plus macrogol increases colorectal volume, but does not improve GI transit compared to PR oxycodone/naloxone. However, PR oxycodone/naloxone results in a lower abdominal symptom burden, despite higher stool frequency during macrogol treatment.

Assessment of colorectal length using the electromagnetic capsule tracking system: A comparative validation study in healthy subjects

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The effect of opioid treatment on colorectal motility assessed by electromagnetic capsules

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Characterization of cortical source generators based on electroencephalography during tonic pain

Objective The aim of the present study was to characterize the cortical source generators evoked by experimental tonic pain. Methods Electroencephalography (EEG) was recorded on two separate days during rest and with immersion of the hand in ice water for 2 minutes (cold pressor test). Exact low-resolution brain electromagnetic tomography source localization was performed in 31 healthy volunteers to characterize the cortical source generators. Results Reliability was high in all eight frequency bands during rest and cold pressor conditions (intraclass coefficients =0.47–0.83 in the cingulate and insula). Tonic pain increased cortical activities in the delta (1–4 Hz), theta (4–8 Hz), beta1 (12–18 Hz), beta2 (18–24 Hz), beta3 (24–32 Hz), and gamma (32–60 Hz) bands (all P<0.011) in widespread areas mainly in the limbic system, whereas decreased cortical activities were found in cingulate and pre- and postcentral gyri in the alpha2 (10–12 Hz) band (P=0.007). The pain intensity was correlated with cingulate activity in the beta2, beta3, and gamma bands (all P<0.04). Conclusion Source localization of EEG is a reliable method to estimate cortical source generators. Activities in different brain regions, mainly in the limbic system, showed fluctuations in various frequency bands. Cingulate changes were correlated with pain intensity. Significance This method might add information to the objective assessment of the cortical pain response in future experimental pain studies.

Non-invasive estimation of respiratory depression profiles during robot-assisted laparoscopic surgery using a model-based approach

Introduction: Robot assisted laparoscopic surgeries are becoming the standard procedure for radical prostatectomies (RALRP). General anesthesia, Trendelenburg positioning and capnoperitoneum during RALRP affect patient’ gas exchange, leading to possible complications in the postoperative phase, such as hypoxemia. The aim of this paper is to examine the changes in pulmonary gas exchange through the perioperative period for RALRP using a mathematical model approach.