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Experimental human pain models in gastro-esophageal reflux disease and unexplained chest pain

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World Journal of Gastroenterology 2006年第18期12卷 2805-2817页

作者： Asbjφrn Mohr Drewes Lars Arendt-Nielsen peter funch-jensen Hans Gregersen Center for Visceral Biomechanics and Pain Department of GastroenterologyAalborg Hospitaland Center for Sensory-Motor InteractionsDepartment of Health Science and TechnologyAalborg UniversityDenmark Department of Surgical Gastroenterology L Aarhus HospitalDenmark

Methods related to experimental human pain research aim at activating different nociceptors, evoke pain from different organs and activate specific pathways and mechanisms. The different possibilities for using mechanical, electrical, thermal and chemical methods in visceral pain research are discussed with emphasis of combinations (e.g., the multimodal approach). The methods have been used widely in assessment of pain mechanisms in the esophagus and have contributed to our understanding of the symptoms reported in these patients. Hence abnormal activation and plastic changes of central pain pathways seem to play a major role in the symptoms in some patients with gastro-esophageal reflux disease and in patients with functional chest pain of esophageal origin. These findings may lead to an alternative approach for treatment in patients that does not respond to conventional medical or surgical therapy.

关键词： Pain Gut Experimental Chest pain Esophagitis

Axial force measurement for esophageal function testing

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World Journal of Gastroenterology 2009年第2期15卷 139-143页

作者： Flemming H Gravesen peter funch-jensen Hans Gregersen Asbjφrn Mohr Drewes Mech-Sense Department of Gastroenterology Aalborg Hospital Aalborg Denmark Center for Sensory-Motor Interaction (SMI) Department of Health Science and Technology Aalborg University DK-9000 Aalborg Denmark Department of Surgical Gastroenterology L rhus University Hospital rhus Denmark

The esophagus serves to transport food and fluid from the pharynx to the stomach. Manometry has been the "golden standard" for the diagnosis of esophageal motility diseases for many decades. Hence, esophageal function is normally evaluated by means of manometry even though it reflects the squeeze force (force in radial direction) whereas the bolus moves along the length of esophagus in a distal direction. Force measurements in the longitudinal (axial) direction provide a more direct measure of esophageal transport function. The technique used to record axial force has developed from external force transducers over in-vivo strain gauges of various sizes to electrical impedance based measurements. The amplitude and duration of the axial force has been shown to be as reliable as manometry. Normal, as well as abnormal, manometric recordings occur with normal bolus transit, which have been documented using imaging modalities such as radiography and scintigraphy. This inconsistency using manometry has also been documented by axial force recordings. This underlines the lack of information when diagnostics are based on manometry alone. Increasing the volume of a bag mounted on a probe with combined axial force and manometry recordings showed that axial force amplitude increased by 130% in contrast to an increase of 30% using manometry. Using axial force in combination with manometry provides a more complete picture of esophageal motility, and the current paper outlines the advantages of using this method.

关键词： Axial force Traction force Manometry Motility Peristalsis Esophageal function

Reversibility of central neuronal changes in patients recovering from gallbladder stones or acute cholecystitis

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World Journal of Gastroenterology 2006年第46期12卷 7522-7526页

作者： Daniel W Kjaer Marek Stawowy Lars Arendt-Nielsen Asbjφrn Mohr Drewes peter funch-jensen Surgical Gastroenterology Department L Aarhus University Hospital Aarhus Denmark Department of Hepato-Gastroenterology V Aarhus University Hospital Aarhus Denmark Center for Sensory-Motor Interactions Department of Health Science and Technology Aalborg University Denmark Department of Medical Gastroenterology Aalborg University Hospital Aalborg Denmark

AIM: To investigate the referred pain area in patients 2-7 years after cholecystectomy in order to test the hypothesis that neuroplastic changes could give rise to post cholecystectomy pain. METHODS: Forty patients were tested. Twenty five were cholecystectomized due to uncomplicated gallbladder stones and 15 because of acute cholecystitis. Sensitivity to pinprick, heat, cold, pressure and single and repeated electrical stimulation was studied both in the referred pain area and in the control area on the contra lateral side of the abdomen. RESULTS: Five patients still intermittently suffered from pain. But in the objective test of the 40 patients, no statistical significant difference was found between the referred pain area and the control area. CONCLUSION: This study does not support the hypothesis that de novo neuroplastic changes could develop several years after cholecys-tectomy.

关键词： Referred pain Hyperalgesia Cholecystitis Post cholecystectomy syndrome

Proximal and distal esophageal sensitivity is decreased in patients with Barrett’s esophagus

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World Journal of Gastroenterology 2011年第4期17卷 514-521页

作者： Anne L Kraru Sφren S Olesen peter funch-jensen Hans Gregersen Asbjφrn M Drewes Mech-Sense Department of Gastroenterology Aalborg Hospital Aarhus University Hospital Department of Surgery L Aarhus University Hospital

AIM: To investigate sensations to multimodal pain stimulation in the metaplastic and normal parts of the esophagus in patients with Barrett’s esophagus (BE). METHODS: Fifteen patients with BE and 15 age-matched healthy volunteers were subjected to mechanical, thermal and electrical pain stimuli of the esophagus. Both the metaplastic part and the normal part (4 and 14 cm, respectively, above the esophago-gastric junction) were examined. At sensory thresholds the stimulation intensity, referred pain areas, and evoked brain potentials were recorded. RESULTS: Patients were hyposensitive to heat stimulation both in the metaplastic part [median stimulation time to reach the pain detection threshold: 15 (12-34) s vs 14 (6-23) s in controls; F = 4.5, P = 0.04] and the normal part of the esophagus [median 17 (6-32) s vs 13 (8-20) s in controls; F = 6.2, P = 0.02]. Furthermore, patients were hyposensitive in the metaplastic part of the esophagus to mechanical distension [median volume at moderate pain: 50 (20-50) mL vs 33 (13-50) mL in controls; F = 5.7, P = 0.02]. No indication of central nervous system abnormalities was present, as responses were comparable between groups to electrical pain stimuli in the metaplastic part [median current evoking moderate pain: 13 (6-26) mA vs 12 (9-24) mA in controls; F = 0.1, P = 0.7], and in the normal part of the esophagus [median current evoking moderate pain: 9 (6-16) mA, vs 11 (5-11) mA in controls; F = 3.4, P = 0.07]. Furthermore, no differences were seen for the referred pain areas (P-values all > 0.3) or latencies and amplitudes for the evoked brain potentials (P-values all > 0.1). CONCLUSION: Patients with BE are hyposensitive both in the metaplastic and normal part of esophagus likely as a result of abnormalities affecting peripheral nerve pathways.

关键词： Barrett’s esophagus Heat Multimodal Pain Sensitivity

Is the pain in chronic pancreatitis of neuropathic origin? Support from EEG studies during experimental pain

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World Journal of Gastroenterology 2008年第25期14卷 4020-4027页

作者： AsbjФrn M Drewes Maciej Gratkowski Saber AK Sami Georg Dimcevski peter funch-jensen Lars Arendt-Nielsen Department of Gastroenterology Aalborg University Hospital Center for Sensory-Motor Interactions (SMI) Department of Health Science and Technology Aalborg University Department of Gastroenterology Haukeland University Hospital Department of Surgical Gastroenterology L Aarhus University Hospital

AIM: To prove the hypothesis that patients with chronic pancreatitis would show increased theta activity during painful visceral stimulation. METHODS: Eight patients and 12 healthy controls underwent an experiment where the esophagus was electrically stimulated at the pain threshold using a nasal endoscope. The electroencephalogram (EEG) was recorded from 64 surface electrodes and "topographic matching pursuit" was used to extract the EEG information in the early brain activation after stimulation. RESULTS: A major difference between controls and patients were seen in delta and theta bands, whereas there were only minor differences in other frequency bands. In the theta band, the patients showed higher activity than controls persisting throughout the 450 ms of analysis with synchronous brain activation betweenthe channels. The main theta components oscillated with 4.4 Hz in the patients and 5.5 Hz in the controls. The energy in the delta (0.5-3.5 Hz) band was higher in the controls, whereas the patients only showed scattered activity in this band. CONCLUSION: The differences in the theta band indicate that neuropathic pain mechanisms are involved in chronic pancreatitis. This has important implications for the understanding and treatment of pain in these patients, which should be directed against drugs with effects on neuropathic pain disorders.

关键词： Chronic Pancreatitis Neuropathic pain Esophagus Thalamocortical system Electroence-phalography

Sensory-motor responses to mechanical stimulation of the esophagus after sensitization with acid

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World Journal of Gastroenterology 2005年第28期11卷 4367-4374页

作者： Asbjφrn Mohr Drewes Hariprasad Reddy Camilla Staahl Jan Pedersen peter funch-jensen Lars Arendt-Nielsen Hans Gregersen Center for Biomechanics and Pain Department of Gastroenterology Aalborg HospitalAarhus University HospitalAalborgDenmark Department of Surgical Gastroenterology L Aarhus University Hospital AarhusDenmark Center for Sensory-Motor Interactions (SMI) Department of Health Science and Technology Aalborg UniversityAalborgDenmark

AIM: Sensitization most likely plays an important role in chronic pain disorders, and such sensitization can be mimicked by experimental acid perfusion of the *** current study systematically investigated the sensory and motor responses of the esophagus to controlled mechanical stimuli before and after ***: Thirty healthy subjects were *** of the distal esophagus with a balloon was performed before and after perfusion with 0.1 mol/L hydrochloric acid for 30 min. An impedance planimetry system was used to measure cross-sectional area,volume, pressure, and tension during the distensions. A new model allowed evaluation of the phasic contractions by the tension during contractions as a function of the initial muscle length before the contraction (comparable to the Frank-Starling law for the heart). Length-tension diagrams were used to evaluate the muscle tone before and after relaxation of the smooth muscle with ***: The sensitization resulted in allodynia and hyperalgesia to the distension volumes, and the degree of sensitization was related to the infused volume of acid. Furthermore, a nearly 50% increase in the evoked referred pain was seen after sensitization. The mechanical analysis demonstrated hyper-reactivity of the esophagus following acid perfusion, with an increased number and force of the phasic contractions, but the muscle tone did not ***: Acid perfusion of the esophagus sensitizes the sensory pathways and facilitates secondary *** new model can be used to study abnormal sensorymotor mechanisms in visceral organs.

关键词： Esophagus Mechanical Sensitization Motility Reflux Pain

Impaired contractility and remodeling of the upper gastrointestinal tract in diabetes mellitus type-1

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World Journal of Gastroenterology 2007年第36期13卷 4881-4890页

作者： Jens BrΦndum FrΦkjΦr SΦren Due Andersen Niels EjskjΦr peter funch-jensen AsbjΦrn Mohr Drewes Hans Gregersen Center for Visceral Biomechanics and Pain Aalborg Hospital Aalborg Denmark Department of Radiology Aalborg Hospital Aalborg Denmark Department of Endocrinology M Aarhus University Hospital Aarhus Denmark Department of Surgical Gastroenterology L Aarhus University Hospital Aarhus Denmark Center for Sensory-Motor Interaction Department of Health Science and Technology Aalborg University Denmark Center for Sensory-Motor Interaction Department of Health Science and Technology Aalborg University Denmark National Center for Ultrasound in Gastro-enterology Haukeland University Hospital Bergen Norway

AIM: To investigate that both the neuronal function of the contractile system and structural apparatus of the gastrointestinal tract are affected in patients with longstanding diabetes and auto mic neuropathy. METHODS: The evoked esophageal and duodenal contractile activity to standardized bag distension was assessed using a specialized ultrasound-based probe. Twelve type-1 diabetic patients with autonomic neuropathy and severe gastrointestinal symptoms and 12 healthy controls were studied. The geometry and biomechanical parameters (strain, tension/stress, and stiffness) were assessed. RESULTS: The diabetic patients had increased frequency of distension-induced contractions (6.0 ± 0.6 vs 3.3 ± 0.5, P 0.14). CONCLUSION: The impaired contractile activity with an imbalance in the distension-induced contractions likely reflects neuronal abnormalities due to autonomic neuropathy. However, structural changes and remodeling of the gastrointestinal tract are also evident and may add to the neuronal changes. This may contribute to the pathophysiology of diabetic gut dysfunction and impact on future management of diabetic patients with gastrointestinal symptoms.

关键词： Diabetes Autonomic Neuropathy Bio- mechanics Contractility Ultrasound Esophagus Duodenum Deformation Stress

Allocation of synchronous condensers for restoration of system short-circuit power

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Journal of Modern Power Systems and Clean Energy 2018年第1期6卷 17-26页

作者： Emanuel MARRAZI Guangya YANG peter WEINREICH-jensen Center for Electric Power and Energy Department of Electrical Engineering Technical University of Denmark Siemens A/S

Modern power systems,employing an increasing number of converter-based renewable energy sources(RES)and decreasing the usage of conventional power plants,are leading to lower levels of short-circuit power and rotational inertia.A solution to this is the employment of synchronous condensers in the grid,in order to provide sufficient short-circuit *** results in the increase of the short-circuit ratio(SCR)at transmission system busbars serving as points of interconnection(POI)to renewable *** of the required capacity and grid-location of the synchronous condensers,is inherently a mixed integer nonlinear optimization problem,which could not be done on manual basis considering each type of machine and all *** study therefore proposes a method of optimal allocation of synchronous condensers in a hypothetic future scenario of a transmission system fed by renewable *** cost of synchronous condenser installations in the system is minimized and the SCRs at the POIs of central renewable power plants are *** method has potential for application on larger grids,aiding grid-integration of RES.

关键词： Short-circuit power Short-circuit ratio Synchronous condenser

Application of the health risk assessment of acetochlor in the development of water quality criteria

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Journal of Environmental Sciences 2021年第12期33卷 48-54页

作者： Wei An Chenhui Sang Kristian Marienlund jensen peter Borgen Sørensen Bin Zhang Min Yang Key Laboratory of Drinking Water Science and Technology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China Sino-Danish College University of Chinese Academy of SciencesBeijing 100190China Department of Bioscience Aarhus UniversityVejlsovej 25PO BOX 314SilkeborgDenmark University of Chinese Academy of Sciences Beijing 100049China Department of Mathematical Sciences Tsinghua UniversityBeijing 100084China

Acetochlor is a widely used herbicide in agricultural production. Studies have shown that acetochlor has obvious environmental hormone effects, and long-term exposure may pose a threat to human health. To quantify the hazards of acetochlor in drinking water, a health risk assessment of acetochlor was conducted in major cities of China based on the data of acetochlor residue concentrations in drinking water. The approach of the Species Sensitivity Distributions(SSD) method is used to extrapolate from animal testing data to reflect worst case human toxicity. Results show that hazard quotients related to acetochlor residues in drinking water for different age groups range from 1.94 × 10-4 to 6.13 × 10-4, so, there are no indication of human risk. Compared to the total estimated hazard quotient from oral intake of acetochlor, the chronic exposure imputed to acetochlor residues in drinking water in China accounts for 0.4%. This paper recommends 0.02 mg/L to be the maximum acetochlor residue concentration level in drinking water and source water criteria.

关键词： Acetochlor Drinking water Source water Contribution rate Species sensitivity distributions(SSD)