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EXPERIMENTAL HUMAN PAIN

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神经解剖学杂志 2001年第B7期17卷 48-50页

作者： lars arendt.nielsen Center for Sensory-Motor Interaction Laboratory for Experimental Pain Research Aalborg University Aalborg Denmark PhD

Aim: The present project is to seek the possible electrical stimulation parameter by which wind-up of withdrawal reflex of rats and set up a appropriate animal model for recording the withdrawal reflex of wind-up phenomenon. Meanwhile, a parallel comparison will be made between the recording of withdrawal reflex and dorsal horn (DH) neuron responses in order to investigate the possible correlation associated with sensory and motor interaction of pain information via simultaneous recording. On the other hand, another comparison

关键词：人体疼痛定量测量病理生理方法电生理测量

THE MERMAID INSTITUTE: BRIDGING SCIENCE AND INDUSTRY IN PAIN RESEARCH

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神经解剖学杂志 2001年第B7期17卷 51-52页

作者： lars arendt.nielsen Center for Sensory-Motor Interaction Laboratory for Experimental Pain Research Aalborg University Aalborg Denmark PhD

Background The market for new drugs and procedures is substantial, and companies will continue to earmark major sums for the development of new drugs for many years to come. Access to the most up-to-date knowledge is therefore essential for the pharmaceutical companies in the competitive race to develop new proprietary drugs. In recent years, the pharmaceutical industry continuously increased their outsourcing strategy

关键词：疼痛研究医药工业 Mermaid研究所研究开发药物实验

Sensory testing of the human gastrointestinal tract

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World Journal of Gastroenterology 2009年第2期15卷 151-159页

作者： Christina Brock lars arendt.nielsen Oliver Wilder-Smith Asbjφrn Mohr Drewes Mech-Sense Department of Gastroenterology Aalborg Hospital DK-9000 Aalborg Denmark Center for Sensory-Motor Interactions Department of Health Science and Technology Aalborg University DK-9000 Aalborg Denmark Pain and Nociception Research Group Department of Anaesthesiology Radboud University Nijmegen Medical Centrethe Netherlands Mech-Sense Department of Gastro-enterology Aalborg Hospital DK-9000 Aalborg Denmark Author

The objective of this appraisal is to shed light on the various approaches to screen sensory information in the human gut. Understanding and characterization of sensory symptoms in gastrointestinal disorders is poor. Experimental methods allowing the investigator to control stimulus intensity and modality, as well as using validated methods for assessing sensory response have contributed to the understanding of pain mechanisms. Mechanical stimulation based on impedance planimetry allows direct recordings of luminal cross-sectional areas, and combined with ultrasound and magnetic resonance imaging, the contribution of different gut layers can be estimated. Electrical stimulation depolarizes free nerve endings non-selectively. Consequently, the stimulation paradigm （single, train, tetanic） influences the involved sensory nerves. Visual controlled electrical stimulation combines the probes with an endoscopic approach, which allows the investigator to inspect and obtain small biopsies from the stimulation site. Thermal stimulation （cold or warm） activates selectively mucosal receptors, and chemical substances such as acid and capsaicin （either alone or in combination） are used to evoke pain and sensitization. The possibility of multimodal （e.g. mechanical, electrical, thermal and chemical） stimulation in different gut segments has developed visceral pain research. The major advantage is involvement of distinctive receptors, various sensory nerves and different pain pathways mimicking clinical pain that favors investigation of central pain mechanisms involved in allodynia, hyperalgesia and referred pain. As impairment of descending control mechanisms partly underlies the pathogenesis in chronic pain, a cold pressor test that indirectly stimulates such control mechanisms can be added. Hence, the methods undoubtedly represent a major step forward in the future characterization and treatment of patients with various diseases of the gut, which provides knowledge to dinicians

关键词： Endoscopy Intestine Experimental Neurophysiology Pain

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

Ultrasonographic study of mechanosensory properties in human esophagus during mechanical distension

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World Journal of Gastroenterology 2006年第28期12卷 4517-4523页

作者： Ejnar larsen Hariprasad Reddy AsbjΦrn Mohr Drewes lars arendt.nielsen Hans Gregersen Department of Radiology Aalborg HospitalAalborg DK-9100Denmark Center for Visceral Biomechanics and Pain Aalborg HospitalAalborg DK-9100Denmark Laboratory for Experimental Pain Research Center for Sensory-Motor InteractionDepartment of Health TechnologyAalborg UniversityAalborg Dk-9100Denmark

TIM： To study the esophageal geometry and mechanosensation using endoscopic ultrasonography during volume-controlled ramp distensions in the distal esophagus. METHODS： Twelve healthy volunteers underwent distension of a bag. During distension up to moderate pain the sensory intensity was assessed on a visual analogue scale （VAS）. The esophageal deformation in terms of multidimensional stretch ratios and strains was calculated at different volumes and VAS levels. Distensions were done before and during administration of the anticholinergic drug butylscopolamine. RESULTS： The stimulus-response （volume-VAS） curve did not differ without or with the administration of butylscopolamine. Analysis of stretch ratios demonstrated tensile stretch in circumferential direction, compression in radial direction and a small tensile stretch in longitudinal direction. A strain gradient existed throughout the esophageal wall with the largest circumferential deformation at the mucosal surface. The sensation intensity increased exponentially as function of the strains. CONCLUSION： The method provides information of esophageal deformation gradients that correlate to the sensation intensity. Hence, it can be used to study mechanosensation in the human esophagus. Further studies are needed to determine the exact deformation stimulus for the esophageal mechanoreceptors.

关键词： Deformation analysis Esophagus Experimental pain Ultrasonography

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

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

Unrestricted Weight Bearing as a Method for Assessment of Nociceptive Behavior in a Model of Tibiofemoral Osteoarthritis in Rats

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Journal of Behavioral and Brain Science 2013年第3期3卷 306-314页

作者： Lise Skott Gregersen Turid Rosland lars arendt.nielsen Garth Whiteside Michele Hummel Center for Sensory-Motor Interaction Aalborg UniversityAalborgODenmark Purdue Pharma LP CranburyUSA

Background: Novel preclinical models for prediction of osteoarthritis-like pain are necessary for the elucidation of osteoarthritis (OA) pathology and for assessment of novel analgesics. A widely used behavioral test in rat models of tibiofemoral OA is hind limb weight bearing (WB). However, this method evaluates WB in an unnaturally restricted manner. The aim of this study was therefore to characterize the Tekscan Pressure Measurement System as a means to assess OA-like tibiofemoral pain in rats by determination of plantar pressure distribution in a more natural and unrestricted position, defined as unrestricted WB. Methods: Intra-articular injections of 1 mg monosodium iodoacetate (MIA) or saline were administrated in the left hind knee of 84 male Sprague Dawley rats. Changes in unrestricted WB between ipsilateral and contralateral hindlimbs were determined. Morphine (5 mg/kg administered subcutaneously) and naproxen (60 mg/kg per-oral) were examined for their ability to reverse WB changes. Results: Changes in hind limb unrestricted WB were observed 14 (P P P Conclusion: This study indicated that unrestricted WB assessed by the Tekscan system can be utilized as a clinically relevant method to assess aberrations in WB induced by intra-articular MIA injections in rodents. Therefore, this system may be useful for understanding the mechanisms of OA pain in humans and may also assist in the discovery of novel pharmacological agents.

关键词： Osteoarthritis Pain Monosodium Iodoacetate Unrestricted Weight Bearing Morphine Naproxen