Background: Depression and ischemic heart disease (IHD) are associated with persistent stress and autonomic nervous system (ANS) dysfunction. The former can be measured by pressure pain sensitivity (PPS) of the sternu...Background: Depression and ischemic heart disease (IHD) are associated with persistent stress and autonomic nervous system (ANS) dysfunction. The former can be measured by pressure pain sensitivity (PPS) of the sternum, and the latter by the PPS and systolic blood pressure (SBP) response to a tilt table test (TTT). Beta-blocker treatment reduces the efferent beta-adrenergic ANS function, and thus, the physiological stress response. Objective: To test the effect of beta-blockers on changes in depression score in patients with IHD, as well as the influence on persistent stress and ANS dysfunction. Methods: Three months of non-pharmacological intervention aiming at reducing PPS and depression score in patients with stable IHD. Beta-blocker users (N = 102) were compared with non-users (N = 75), with respect to signs of depression measured by the Major Depressive Inventory questionnaire (MDI), resting PPS, and PPS and SBP response to TTT. Results: MDI score decreased 30% in non-users (p = 0.005) compared to 4% (p > 0.1) among users (between-group p = 0.003;effect size = 0.4). Resting PPS decreased in both the groups. Among most vulnerable patients with MDI ≥ 15, reductions in MDI score and resting PPS score correlated in non-users, only (r = 0.69, p = 0.007). Reduction in resting PPS correlated with an increase in PPS and SBP response to TTT. Conclusions: Stress intervention in patients with IHD was anti-depressive in non-users, only. Similarly, the association between the reduction in depression, reduction in persistent stress, and restoration of ANS dysfunction was only seen in non-users, suggesting a central role of beta-adrenergic receptors in the association between these factors.展开更多
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 mechan...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.展开更多
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 whe...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.展开更多
AIM: Sensitization most likely plays an important role in chronic pain disorders, and such sensitization can be mimicked by experimental acid perfusion of the esophagus.The current study systematically investigated th...AIM: Sensitization most likely plays an important role in chronic pain disorders, and such sensitization can be mimicked by experimental acid perfusion of the esophagus.The current study systematically investigated the sensory and motor responses of the esophagus to controlled mechanical stimuli before and after sensitization.METHODS: Thirty healthy subjects were included.Distension 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 butylscopolamine.RESULTS: 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 change.CONCLUSION: Acid perfusion of the esophagus sensitizes the sensory pathways and facilitates secondary contractions.The new model can be used to study abnormal sensorymotor mechanisms in visceral organs.展开更多
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. ...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 clinicians about the underlying symptoms and treatment of these patients.展开更多
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 phen...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展开更多
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 we...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.展开更多
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 ...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展开更多
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 phen...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展开更多
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 ...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.展开更多
文摘Background: Depression and ischemic heart disease (IHD) are associated with persistent stress and autonomic nervous system (ANS) dysfunction. The former can be measured by pressure pain sensitivity (PPS) of the sternum, and the latter by the PPS and systolic blood pressure (SBP) response to a tilt table test (TTT). Beta-blocker treatment reduces the efferent beta-adrenergic ANS function, and thus, the physiological stress response. Objective: To test the effect of beta-blockers on changes in depression score in patients with IHD, as well as the influence on persistent stress and ANS dysfunction. Methods: Three months of non-pharmacological intervention aiming at reducing PPS and depression score in patients with stable IHD. Beta-blocker users (N = 102) were compared with non-users (N = 75), with respect to signs of depression measured by the Major Depressive Inventory questionnaire (MDI), resting PPS, and PPS and SBP response to TTT. Results: MDI score decreased 30% in non-users (p = 0.005) compared to 4% (p > 0.1) among users (between-group p = 0.003;effect size = 0.4). Resting PPS decreased in both the groups. Among most vulnerable patients with MDI ≥ 15, reductions in MDI score and resting PPS score correlated in non-users, only (r = 0.69, p = 0.007). Reduction in resting PPS correlated with an increase in PPS and SBP response to TTT. Conclusions: Stress intervention in patients with IHD was anti-depressive in non-users, only. Similarly, the association between the reduction in depression, reduction in persistent stress, and restoration of ANS dysfunction was only seen in non-users, suggesting a central role of beta-adrenergic receptors in the association between these factors.
基金Supported by Det Obelske Familiefond and Spar Nord Fonden
文摘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.
基金"Nordjyllands Amts Forskningslegat" and the Danish Technical Research Council
文摘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.
基金Supported by the "Det Obelske Familifond", "Spar Nord Fonden"and the Danish Technical Research Council
文摘AIM: Sensitization most likely plays an important role in chronic pain disorders, and such sensitization can be mimicked by experimental acid perfusion of the esophagus.The current study systematically investigated the sensory and motor responses of the esophagus to controlled mechanical stimuli before and after sensitization.METHODS: Thirty healthy subjects were included.Distension 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 butylscopolamine.RESULTS: 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 change.CONCLUSION: Acid perfusion of the esophagus sensitizes the sensory pathways and facilitates secondary contractions.The new model can be used to study abnormal sensorymotor mechanisms in visceral organs.
基金Supported by Det Obelske Familie fond and Spar Nord Fonden
文摘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 clinicians about the underlying symptoms and treatment of these patients.
文摘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
文摘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.
文摘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
文摘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
文摘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.