RESUMEN
BACKGROUND: Esophageal hyposensitivity has been observed in Barrett's esophagus and may contribute to its pathophysiology. However, studies are few, in particular those assessing different sensory modalities. We aimed to compare esophageal sensitivity to multimodal stimulation in patients with Barrett's esophagus and in healthy controls. METHODS: Twenty-three patients with Barrett's esophagus and 12 healthy controls were examined. A multimodal probe was placed in the lower esophagus. Mechanical, thermal, and electrical stimulation was applied followed by an acid perfusion test with 0.1 N hydrochloric acid. KEY RESULTS: Compared with controls, patients were hyposensitive to mechanical distension, heat, and electrical stimulation (all P<.05), but hypersensitive to acid (mean tolerated acid volume 57% lower, P=.001). A linear correlation between acid hypersensitivity and lower baseline impedance was found (P<.001). Patients had longer esophageal acid exposure time than controls (median acid exposure time 18 vs 5%, P=.03). Asymptomatic patients (no reflux symptoms at baseline) were hyposensitive to mechanical distension, electrical stimulation, and acid perfusion (all P<.05) compared with symptomatic patients. CONCLUSIONS & INFERENCES: Patients with Barrett's esophagus exhibited acid hypersensitivity but hyposensitivity to other stimuli. Lower mucosal baseline impedance, a likely surrogate marker for impaired mucosal integrity, may explain the selective hypersensitivity to acid. On the other hand, the concurrent hyposensitivity may theoretically be explained by changes in central pain modulation. Patients with Barrett's esophagus seem to compose symptomatic and asymptomatic subgroups, showing different esophageal sensory profiles.
Asunto(s)
Esófago de Barrett/fisiopatología , Esófago/efectos de los fármacos , Esófago/fisiopatología , Calor/efectos adversos , Ácido Clorhídrico/farmacología , Estimulación Física/efectos adversos , Adulto , Anciano , Esófago de Barrett/diagnóstico , Estimulación Eléctrica/efectos adversos , Estimulación Eléctrica/métodos , Femenino , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Estimulación Física/métodosRESUMEN
BACKGROUND: Functional chest pain (FCP) of presumed esophageal origin is considered a common cause for chest pain in which central nervous system hyperexcitability is thought to play an important role. We aimed to compare cerebral responses with painful esophageal stimuli between FCP patients and healthy subjects (HS). METHODS: Thirteen patients with FCP (seven females, mean age 50.4 ± 7.5 years) and 15 HS (eight females, mean age 49.1 ± 12.9 years) were enrolled. Inclusion criteria consisted of typical chest pain, normal coronary angiogram, and normal upper gastrointestinal evaluation. Electrical stimulations evoking the pain threshold were applied in the distal esophagus, while cortical evoked potentials were recorded from the scalp. Pain scores, resting electroencephalogram (EEG), evoked potential characteristics and brain electrical sources to pain stimulation were compared between groups. KEY RESULTS: No differences were seen between patients and HS regarding (i) pain thresholds (patients: 20.1 ± 7.4 mA vs HS: 22.4 ± 8.3 mA, all P > 0.05), (ii) resting-EEG (P > 0.05), (iii) evoked brain potential latencies (N2: patients 181.7 ± 25.7 mS vs HS 182.2 ± 25.8 mS, all P > 0.05) and amplitudes (N2P2: patients 8.2 ± 7.2 µV vs HS: 10.1 ± 3.4 µV, all P > 0.05), (iv) topography (P > 0.05), and (v) brain source location (P > 0.05). CONCLUSIONS & INFERENCES: No differences in activation of brain areas to painful esophageal stimulation were seen in this group of well characterized patients with FCP compared with sex- and age-matched HS. The mechanism of pain in FCP and whether it originates in the esophagus remains unsolved.
Asunto(s)
Corteza Cerebral/fisiopatología , Dolor en el Pecho/fisiopatología , Esófago/fisiopatología , Estimulación Eléctrica , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del DolorRESUMEN
BACKGROUND: Clinical data suggest gender differences in gastrointestinal pain, but very little experimental data exist. Esophageal painful thresholds to mechanical, thermal, electric, and chemical stimuli can be measured with the esophageal multimodal pain model. The aim was to measure the effect of gender and mild esophagitis on esophageal pain perception. METHODS: Thirty-five healthy asymptomatic volunteers [19 men, median age 29 (22-56 years)] underwent upper GI endoscopy, 24 h pH/impedance measurement, and multimodal esophageal pain stimulation before and after sensitization with acid. Stimulus intensities at painful thresholds were recorded. KEY RESULTS: Men had higher pain thresholds (PT) to mechanical stimulation (mean volume: men 20.9 ± 10 mL vs women 15.2 ± 6.8 mL, P = 0.02) and more men tolerated the maximum acid challenge (58% vs 20%, P = 0.03). There were no differences between genders for PT to (1) thermal stimulation [mean stimulation time (men, women): heat; 20 ± 5 s vs 21 ± 6 s or cold; 33.3 ± 20.1 s vs 20.7 ± 21.4 s, P > 0.2], (2) electrical current (mean current: men 17.6 ± 9.2 mA vs women 12.9 ± 3.7 mA, P = 0.11), or (3) acid volume [median volume: men 200 (20;200) mL vs women 133 (40;200) mL, P = 0.2]. Fifteen asymptomatic subjects had mild esophagitis (10 men, all Los Angeles A). There were no differences in esophageal PT between subjects with normal endoscopy or mild esophagitis (all P > 0.3). CONCLUSIONS & INFERENCES: The effects of gender and mild esophagitis on esophageal multimodal pain perception have been measured in asymptomatic volunteers. The study suggests that gender, not mild esophagitis, tends to influence mechanical and chemical esophageal pain.
Asunto(s)
Esófago/fisiología , Umbral del Dolor/fisiología , Caracteres Sexuales , Ácidos/efectos adversos , Adulto , Esofagitis/inducido químicamente , Esofagitis/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Many patients with gastro-oesophageal reflux disease (GERD) are hypersensitive to heat and acid and may respond insufficiently to standard treatment. Antagonists of the heat and acid receptor 'transient receptor potential vanilloid 1'(TRPV1) are a potential drug class for GERD treatment. AIM: To investigate the effect of a TRPV1 antagonist (AZD1386) on experimentally induced oesophageal pain. METHODS: Twenty-two healthy men (20-31 years) participated in this randomised, placebo-controlled, double-blinded, crossover study examining the effects of a single-dose oral AZD1386 (30 and 95 mg). Subjects were block-randomised. On treatment days, participants were stimulated with painful heat, distension, electrical current and acid in the oesophagus. Heat and pressure pain on the forearm were somatic control stimuli. DATA ANALYSIS: intention-to-treat. RESULTS: A total of 21 participants completed the protocol and 1 voluntarily discontinued. In the oesophagus, both 30 and 95 mg of AZD1386 increased pain thresholds to heat stimuli 23% [95% confidence interval (CI): 10-38%] and 28%, respectively (CI: 14-43%). The skin heat tolerance was increased 2.1 °C (CI: 1.1-3.2 °C) after 30 mg AZD1386 and 4.0 °C (CI: 3.0-5.0 °C) after 95 mg. Heat analgesia persisted for 2.5 h. Pain thresholds to the other stimuli were unaffected by AZD1386. 50% reported 'feeling cold' and body temperature increased in all subjects exposed to 30 and 95 mg AZD1386 (mean increase 0.4±0.3 °C and 0.7±0.3 °C, respectively, P<0.05). CONCLUSIONS: AZD1386 increased oesophageal and skin heat pain thresholds and had a safe adverse-event profile. This drug class may have a potential for treatment of GERD.
Asunto(s)
Analgésicos/uso terapéutico , Enfermedades del Esófago/tratamiento farmacológico , Hiperalgesia/tratamiento farmacológico , Canales Catiónicos TRPV/antagonistas & inhibidores , Adulto , Analgésicos/farmacocinética , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Enfermedades del Esófago/inducido químicamente , Calor , Humanos , Hiperalgesia/inducido químicamente , Masculino , Dolor/tratamiento farmacológico , Dimensión del Dolor , Adulto JovenRESUMEN
Painful sensations from the gastrointestinal (GI) tract are common symptoms in the clinic but the etiology is often not fully understood and underlying diseases can be difficult to diagnose and treat successfully. In clinical practice, GI pain is often diffuse and pain referral to somatic structures can be the presenting symptom. In addition, concomitant symptoms from the autonomic and enteric nervous system can be present and affect the pain experience. To examine patients suffering from GI pain, basic knowledge about the GI pain system is essential and assists to explain the often complex and diverse symptoms. Information about anatomical and physiological characteristics of the GI pain system come from basic, experimental and clinical research, which have also gained insight into pain mechanisms underlying chronic GI pain. Evidence for sensitisation at the peripheral and central level of the nervous system seems to be of importance. These findings have major implication for the evaluation and treatment of patients suffering from GI pain.
Asunto(s)
Enfermedades Gastrointestinales/complicaciones , Dolor/etiología , Vías Aferentes , Enfermedad Crónica , Enfermedades Gastrointestinales/fisiopatología , Tracto Gastrointestinal/inervación , Humanos , Sensación , Médula EspinalRESUMEN
Pain mechanisms in patients with chronic pancreatitis are incompletely understood and probably multifactorial. Recently, evidence from experimental human pain research has indicated that in many of these patients pain processing in the central nervous system is abnormal and mimics that seen in neuropathic pain disorders. The current review focuses on several lines of evidence supporting this hypothesis. Hence, the spontaneous and postprandial pain in chronic pancreatitis may reflect the characteristic pain features seen in patients with neuropathic pain. Biochemical and histopathological findings in tissues from patients with chronic pancreatitis are similar to those observed in patients with other nerve fibre lesions. Experimental studies have shown that patients with chronic pancreatitis show signs of spinal hyper-excitability counter-balanced by segmental and descending inhibition. Changes in the brain with cortical reorganisation to gut stimulation and increased activity in specific electroencephalographic features characteristic for neuropathic pain are also seen in patients with chronic pancreatitis. Finally, principles involved in the treatment of pancreatic pain have many similarities with those recommended in neuropathic pain disorders. In conclusion, a mechanism-based understanding of pain in chronic pancreatitis may have important implications for the treatment.
Asunto(s)
Dolor Abdominal/fisiopatología , Dimensión del Dolor/métodos , Umbral del Dolor/fisiología , Pancreatitis Crónica/fisiopatología , Dolor Abdominal/etiología , Vías Aferentes/fisiología , Animales , Progresión de la Enfermedad , Potenciales Evocados , Humanos , Pancreatitis Crónica/complicaciones , Sistema Nervioso Periférico/fisiopatología , Periodo Posprandial , Índice de Severidad de la EnfermedadRESUMEN
A new method for measuring the anterior translation in the shoulder joint by dynamic ultrasound was evaluated. We placed a 3.5-MHz transducer on the shoulder anteriorly. By using 3 bony landmarks, we then measured the anterior translation of the humeral head with a force of 90 N applied posteriorly. We performed such measurements in 20 subjects with healthy shoulders and in 20 patients with unilateral shoulder instability. There was a mean translation of 1.9 mm in healthy shoulders and 4.9 mm in unstable shoulders (P < .01). The mean difference between the 2 sides in subjects with normal shoulders was 0.7 mm, whereas the mean difference in patients with instability was 2.8 mm (P < .01). The normal shoulders were examined by 2 examiners to determine the degree to which different examiners' measurements might vary. Although one examiner recorded higher values than the other, the new method seems suitable for measuring increased laxity in unstable shoulders.
Asunto(s)
Luxaciones Articulares , Inestabilidad de la Articulación/diagnóstico por imagen , Articulación del Hombro/diagnóstico por imagen , Ultrasonografía/métodos , Adolescente , Adulto , Femenino , Humanos , Húmero/anatomía & histología , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Rango del Movimiento Articular , Lesiones del Hombro , Ultrasonografía/normasRESUMEN
Adverse effects of perioperative blood transfusion appear to be storage-time-dependent and may be related to extracellular accumulation of bioactive substances in blood products. In this study the clinical effects of leukofiltered and non-filtered blood products in patients undergoing surgery for burn trauma are investigated. 24 consecutive patients were randomly selected to receive transfusion with non-filtered blood components (group A, n = 12) or similar products, which were prestorage leukofiltered (group B, n = 12). The burn injury was scored using the Bull and Fischer index of age and burn surface area. Histamine, interleukin-6 (IL-6), plasminogen activator inhibitor-1 (PAI-1), eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were analysed in plasma or serum collected from all patients 30 min before skin incision, at skin incision and 5, 10 and 30 min and thereafter every 30 min after skin incision until the grafts were secured by wrapping. Samples were also taken 8 h after skin incision and in the morning of postoperative days 1-5. The amount of blood products transfused from admission until day 5 postoperatively was recorded. All patients were followed until discharge or death. The Bull and Fischer index was comparable in the two groups. Prestorage leukofiltration reduced the amount of blood products required for transfusion significantly (p < 0.05) compared with non-filtered products. The levels of the various bioactive substances changed during and after the operation. In particular, ECP and MPO levels increased significantly (p < 0.05) in group A patients compared with unchanged (ECP) or decreased (MPO) levels in group B patients. IL-6 analyses showed, that the trauma had more severe impact on group B patients than on group A patients. Nevertheless, 4 patients died in group A and 2 in group B; all with a Bull and Fischer index between 1.0 and 2.0. Prestorage leukocyte filtration may reduce transfusion related accumulation of various bioactive substances and the requirement for blood in burn trauma patients.