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
Chronic pancreatitis(CP)is an inflammatory disease of the pancreas characterized by progressive fibrotic destruction of the pancreatic secretory parenchyma.Despite the heterogeneity in pathogenesis and involved risk f...Chronic pancreatitis(CP)is an inflammatory disease of the pancreas characterized by progressive fibrotic destruction of the pancreatic secretory parenchyma.Despite the heterogeneity in pathogenesis and involved risk factors,processes such as necrosis/apoptosis,inflammation or duct obstruction are involved.This fibrosing process ultimately leads to progressive loss of the lobular morphology and structure of the pancreas,deformation of the large ducts and severe changes in the arrangement and composition of the islets.These conditions lead to irreversible morphological and structural changes resulting in impairment of both exocrine and endocrine functions.The prevalence of the disease is largely dependent on culture and geography.The etiological risk-factors associated with CP are multiple and involve both genetic and environmental factors.Throughout this review the M-ANNHEIM classification system will be used,comprising a detailed description of risk factors such as:alcohol-consumption,nicotineconsumption,nutritional factors,hereditary factors,efferent duct factors,immunological factors and miscellaneous and rare metabolic factors.Increased knowledge of the different etiological factors may encourage the use of further advanced diagnostic tools,which potentially will help clinicians to diagnose CP at an earlier stage.However,in view of the multi factorial disease and the complex clinical picture,it is not surprising that treatment of patients with CP is challenging and often unsuccessful.展开更多
Despite multiple theories on the pathogenesis of pain in chronic pancreatitis,no uniform and consistently successful treatment strategy exists and abdominal pain still remains the dominating symptom for most patients ...Despite multiple theories on the pathogenesis of pain in chronic pancreatitis,no uniform and consistently successful treatment strategy exists and abdominal pain still remains the dominating symptom for most patients and a major challenge for clinicians.Traditional theories focussed on a mechanical cause of pain related to anatomical changes and evidence of increased ductal and interstitial pressures.These observations form the basis for surgical and endoscopic drainage procedures,but the outcome is variable and often unsatisfactory.This underscores the fact that other factors must contribute to pathogenesis of pain,and has shifted the focus towards a more complex neurobiological understanding of pain generation.Amongst other explanations for pain,experimental and human studies have provided evidence that pain perception at the peripheral level and central pain processing of the nociceptive information is altered in patients with chronic pancreatitis,and resembles that seen in neuropathic and chronic pain disorders.However,pain due to e.g.,complications to the disease and adverse effects to treatment must not be overlooked as an additional source of pain.This review outlines the current theories on pain generation in chronic pancreatitis which is crucial in order to understand the complexity and limitations of current therapeutic approaches.Furthermore,it may also serve as an inspiration for further research and development of methods that can evaluate the relative contribution and interplay of different pain mechanisms in the individual patients,before they are subjected to more or less empirical treatment.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
Understanding and characterization of pain and other sensory symptoms are among the most important issues in the diagnosis and assessment of patient with gastrointestinal disorders. Methods to evoke and assess experim...Understanding and characterization of pain and other sensory symptoms are among the most important issues in the diagnosis and assessment of patient with gastrointestinal disorders. Methods to evoke and assess experimental pain have recently developed into a new area with the possibility for multimodal stimulation （e.g., electrical, mechanical, thermal and chemical stimulation） of different nerves and pain pathways in the human gut. Such methods mimic to a high degree the pain experienced in the clinic. Multimodal pain methods have increased our basic understanding of different peripheral receptors in the gut in health and disease. Together with advanced muscle analysis, the methods have increased our understanding of receptors sensitive to mechanical, chemical and temperature stimuli in diseases, such as systemic sclerosis and diabetes. The methods can also be used to unravel central pain mechanisms, such as those involved in allodynia, hyperalgesia and referred pain. Abnormalities in central pain mechanisms are often seen in patients with chronic gut pain and hence methods relying on multimodal pain stimulation may help to understand the symptoms in these patients. Sex differences have been observed in several diseases of the gut, and differences in central pain processing between males and females have been hypothesized using multimodal pain stimulations. Finally, multimodal methods have recently been used to gain more insight into the effect of drugs against pain in the GI tract. Hence, the multimodal methods undoubtedly represents a major step forward in the future characterization and treatment of patients with various diseases of the gut.展开更多
Low-level laser therapy(LLLT) may have an effect on the pain associated with orthodontic treatment. The aim of this study was to evaluate the effect of LLLT on pain and somatosensory sensitization induced by orthodont...Low-level laser therapy(LLLT) may have an effect on the pain associated with orthodontic treatment. The aim of this study was to evaluate the effect of LLLT on pain and somatosensory sensitization induced by orthodontic treatment. Forty individuals(12–33 years old; mean ± standard deviations: 20.8 ± 5.9 years) scheduled to receive orthodontic treatment were randomly divided into a laser group(LG) or a placebo group(PG)(1:1). The LG received LLLT(810-nm gallium-aluminium-arsenic diode laser in continuous mode with the power set at 400 mW, 2 J·cm–2) at 0 h, 2 h, 24 h, 4 d, and 7 d after treatment, and the PG received inactive treatment at the same time points. In both groups, the non-treated side served as a control. A numerical rating scale(NRS) of pain, pressure pain thresholds(PPTs), cold detection thresholds(CDTs), warmth detection thresholds(WDTs), cold pain thresholds(CPTs), and heat pain thresholds(HPTs) were tested on both sides at the gingiva and canine tooth and on the hand. The data were analysed by a repeated measures analysis of variance(ANOVA). The NRS pain scores were significantly lower in the LG group(P = 0.01). The CDTs,CPTs, WDTs, HPTs, and PPTs at the gingiva and the PPTs at the canine tooth were significantly less sensitive on the treatment side of the LG compared with that of the PG(P < 0.033). The parameters tested also showed significantly less sensitivity on the nontreatment side of the LG compared to that of the PG(P < 0.043). There were no differences between the groups for any quantitative sensory testing(QST) measures of the hand. The application of LLLT appears to reduce the pain and sensitivity of the tooth and gingiva associated with orthodontic treatment and may have contralateral effects within the trigeminal system but no generalized QST effects. Thus, the present study indicated a significant analgesia effect of LLLT application during orthodontic treatment.Further clinical applications are suggested.展开更多
Imaging of the gastrointestinal tract is very useful for research and clinical studies of patients with symptoms arising from the gastrointestinal tract and in visualising anatomy and pathology. Traditional radiologic...Imaging of the gastrointestinal tract is very useful for research and clinical studies of patients with symptoms arising from the gastrointestinal tract and in visualising anatomy and pathology. Traditional radiological techniques played a leading role in such studies for a long time. However, advances in non-invasive modalities including ultrasound (US), computed tomography (CT), positron emission tomography (PET), magnetic resonance imaging (MRI), etc, have in the last decades revolutionised the way in which the gastrointestinal tract is studied. The resolution of imaging data is constantly being improved and 3D acquisition, tools for fi ltering, enhancement, segmentation and tissue classif ication are continually being developed. Additional co-registration techniques allow multimodal data acquisition with improved classif ication of tissue pathology. Furthermore, new functional imaging techniques have become available. Altogether, the future of gastrointestinal imaging looks very promising which will be of great benef it in clinical and research studies of gastrointestinal diseases. The purpose of this review is to highlight the capabilities of the newest techniques to explore the detailed morphology, biomechanical properties, function and pathology of the gastrointestinal tract.展开更多
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, esophagea...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.展开更多
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 The Danish Council for Strategic Research
文摘Chronic pancreatitis(CP)is an inflammatory disease of the pancreas characterized by progressive fibrotic destruction of the pancreatic secretory parenchyma.Despite the heterogeneity in pathogenesis and involved risk factors,processes such as necrosis/apoptosis,inflammation or duct obstruction are involved.This fibrosing process ultimately leads to progressive loss of the lobular morphology and structure of the pancreas,deformation of the large ducts and severe changes in the arrangement and composition of the islets.These conditions lead to irreversible morphological and structural changes resulting in impairment of both exocrine and endocrine functions.The prevalence of the disease is largely dependent on culture and geography.The etiological risk-factors associated with CP are multiple and involve both genetic and environmental factors.Throughout this review the M-ANNHEIM classification system will be used,comprising a detailed description of risk factors such as:alcohol-consumption,nicotineconsumption,nutritional factors,hereditary factors,efferent duct factors,immunological factors and miscellaneous and rare metabolic factors.Increased knowledge of the different etiological factors may encourage the use of further advanced diagnostic tools,which potentially will help clinicians to diagnose CP at an earlier stage.However,in view of the multi factorial disease and the complex clinical picture,it is not surprising that treatment of patients with CP is challenging and often unsuccessful.
基金Supported by The Danish Council for Strategic Research
文摘Despite multiple theories on the pathogenesis of pain in chronic pancreatitis,no uniform and consistently successful treatment strategy exists and abdominal pain still remains the dominating symptom for most patients and a major challenge for clinicians.Traditional theories focussed on a mechanical cause of pain related to anatomical changes and evidence of increased ductal and interstitial pressures.These observations form the basis for surgical and endoscopic drainage procedures,but the outcome is variable and often unsatisfactory.This underscores the fact that other factors must contribute to pathogenesis of pain,and has shifted the focus towards a more complex neurobiological understanding of pain generation.Amongst other explanations for pain,experimental and human studies have provided evidence that pain perception at the peripheral level and central pain processing of the nociceptive information is altered in patients with chronic pancreatitis,and resembles that seen in neuropathic and chronic pain disorders.However,pain due to e.g.,complications to the disease and adverse effects to treatment must not be overlooked as an additional source of pain.This review outlines the current theories on pain generation in chronic pancreatitis which is crucial in order to understand the complexity and limitations of current therapeutic approaches.Furthermore,it may also serve as an inspiration for further research and development of methods that can evaluate the relative contribution and interplay of different pain mechanisms in the individual patients,before they are subjected to more or less empirical treatment.
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 "Det Obelske Familiefond" & "Spar Nord Fonden"
文摘Understanding and characterization of pain and other sensory symptoms are among the most important issues in the diagnosis and assessment of patient with gastrointestinal disorders. Methods to evoke and assess experimental pain have recently developed into a new area with the possibility for multimodal stimulation （e.g., electrical, mechanical, thermal and chemical stimulation） of different nerves and pain pathways in the human gut. Such methods mimic to a high degree the pain experienced in the clinic. Multimodal pain methods have increased our basic understanding of different peripheral receptors in the gut in health and disease. Together with advanced muscle analysis, the methods have increased our understanding of receptors sensitive to mechanical, chemical and temperature stimuli in diseases, such as systemic sclerosis and diabetes. The methods can also be used to unravel central pain mechanisms, such as those involved in allodynia, hyperalgesia and referred pain. Abnormalities in central pain mechanisms are often seen in patients with chronic gut pain and hence methods relying on multimodal pain stimulation may help to understand the symptoms in these patients. Sex differences have been observed in several diseases of the gut, and differences in central pain processing between males and females have been hypothesized using multimodal pain stimulations. Finally, multimodal methods have recently been used to gain more insight into the effect of drugs against pain in the GI tract. Hence, the multimodal methods undoubtedly represents a major step forward in the future characterization and treatment of patients with various diseases of the gut.
基金funded by the Priority Academic Program Development of Jiangsu Higher Education Institution(Grant No.2014-37)the Jiangsu Provincial Health and Family Planning Commission(No.H201535)Orofacial Pain and TMD Research Unit,Institute of Stomatology,Affiliated Hospital of Stomatology,Nanjing Medical University,for their support
文摘Low-level laser therapy(LLLT) may have an effect on the pain associated with orthodontic treatment. The aim of this study was to evaluate the effect of LLLT on pain and somatosensory sensitization induced by orthodontic treatment. Forty individuals(12–33 years old; mean ± standard deviations: 20.8 ± 5.9 years) scheduled to receive orthodontic treatment were randomly divided into a laser group(LG) or a placebo group(PG)(1:1). The LG received LLLT(810-nm gallium-aluminium-arsenic diode laser in continuous mode with the power set at 400 mW, 2 J·cm–2) at 0 h, 2 h, 24 h, 4 d, and 7 d after treatment, and the PG received inactive treatment at the same time points. In both groups, the non-treated side served as a control. A numerical rating scale(NRS) of pain, pressure pain thresholds(PPTs), cold detection thresholds(CDTs), warmth detection thresholds(WDTs), cold pain thresholds(CPTs), and heat pain thresholds(HPTs) were tested on both sides at the gingiva and canine tooth and on the hand. The data were analysed by a repeated measures analysis of variance(ANOVA). The NRS pain scores were significantly lower in the LG group(P = 0.01). The CDTs,CPTs, WDTs, HPTs, and PPTs at the gingiva and the PPTs at the canine tooth were significantly less sensitive on the treatment side of the LG compared with that of the PG(P < 0.033). The parameters tested also showed significantly less sensitivity on the nontreatment side of the LG compared to that of the PG(P < 0.043). There were no differences between the groups for any quantitative sensory testing(QST) measures of the hand. The application of LLLT appears to reduce the pain and sensitivity of the tooth and gingiva associated with orthodontic treatment and may have contralateral effects within the trigeminal system but no generalized QST effects. Thus, the present study indicated a significant analgesia effect of LLLT application during orthodontic treatment.Further clinical applications are suggested.
文摘Imaging of the gastrointestinal tract is very useful for research and clinical studies of patients with symptoms arising from the gastrointestinal tract and in visualising anatomy and pathology. Traditional radiological techniques played a leading role in such studies for a long time. However, advances in non-invasive modalities including ultrasound (US), computed tomography (CT), positron emission tomography (PET), magnetic resonance imaging (MRI), etc, have in the last decades revolutionised the way in which the gastrointestinal tract is studied. The resolution of imaging data is constantly being improved and 3D acquisition, tools for fi ltering, enhancement, segmentation and tissue classif ication are continually being developed. Additional co-registration techniques allow multimodal data acquisition with improved classif ication of tissue pathology. Furthermore, new functional imaging techniques have become available. Altogether, the future of gastrointestinal imaging looks very promising which will be of great benef it in clinical and research studies of gastrointestinal diseases. The purpose of this review is to highlight the capabilities of the newest techniques to explore the detailed morphology, biomechanical properties, function and pathology of the gastrointestinal tract.
基金Supported by Det Obelske Familiefond and Spar Nord Fonden
文摘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.
