胃食管反流病发病中食管内脏感觉调控的研究进展

胃食管反流病（gastroesophageal reflux disease，GERD）是指胃／十二指肠内容物反流到食管引起烧心、反酸等症状和（或）并发症的一种疾病。胃食管反流病是一种常见疾病，通过内镜检查存在食管黏膜损害者称为反流性食管炎（reflux esophagitis，RE）；根据罗马Ⅲ标准，内镜下未见明显食管黏膜损伤者且符合以下任一项者为非糜烂性反流病（non-erosive reflux disease，NERD）：（1）24h胃食管pH监测阳性者；（2）24h胃食管pH监测阴性但症状指数（symptom index）阳性者；（3）24h胃食管pH监测及症状指数均阴性；但质子泵抑制剂（PPI）诊断性治疗（PPI试验）有效者。NERD在GERD中占有较大比例。烧心是GERD的典型症状，发病率较高。群体调查研究显示，在北欧，烧心的发病率为38％，美国更高达42％。症状每月发作1次以上者超过40％，每周发作1次以上者达20％，每日均有症状者约7％。一项在日本进行的结合内镜检查的研究中，2760人参与了调查，结果显示GERD的发病率17，9％，NERD的发病率达10．9％（占GERD的60．6％）。另一项在中（国）、     

迷走传入神经功能异常在内脏高敏感形成中的作用

目的:初步探讨迷走传入神经在醋酸诱导的结肠敏感鼠模型内脏高敏感形成中的作用.方法:采用乳大鼠于出生第10天给予0.5%醋酸灌肠,建立慢性内脏高敏感动物模型,观察直肠内球囊扩张(colorectal distension,CRD)下腹壁撤离反射(withdrawal reflex,AWR)及腹外斜肌放电活动(electromyography,EMG)的变化,评估内脏敏感性.采用电生理学方法记录大鼠颈部迷走传入神经自发放电,观察在CRD下模型组与对照组大鼠迷走神经放电活动.免疫组织化学法观察大鼠孤束核及结肠中c-fos分布及表达情况.结果:与对照组相比,模型组AWR评分及EMG幅值显著增高(P<0.05),HE染色及MPO水平显示两组大鼠结肠均无明显炎症表现,结果提示内脏高敏感模型鼠建立;给予直肠内球囊扩张后模型组迷走神经放电活动明显高于对照组(P<0.05);与对照组相比,模型组大鼠孤束核及结肠肌间神经丛中c-fos表达明显增加(孤束核15.00%±1.85%vs47.30%±2.79%,近端结肠1.00%±0.12%%vs1.90%±0.17%,中端结肠1.10%±0.17%vs1.90%±0.18%,远端结肠1.10%±0.12%vs2.10%±0.17%,均P<0.01).结论:乳鼠醋酸灌肠诱导形成的内脏高敏模型大鼠迷走神经活化存在异常.     

内脏感觉研究进展

胃肠道功能失调最初归因于胃肠动力异常。然而,即使是健康个体,强烈的情感或环境刺激也能使其食管、胃、小肠和结肠的运动增加。胃肠道功能紊乱仅在胃肠动力异常的基础上难以解释。本文介绍内脏感觉研究的一些新进展,并对内脏感觉产生的机理进行阐述。     

内脏感觉过敏与功能性胃肠病

内脏感觉过敏是功能性胃肠病发生的重要病理生理机制之一,主要包括有：(1)正常人不被感知的生理刺激,在疾病情况下被感知,引起腹胀、不适、早饱等;(2)对伤害性刺激反应强烈,引起剧烈的疼痛。内脏感觉过敏在胃肠道功能性病的作用越来越受到关注,了解两者的关系对临床医生也越来越重要。     

食管酸刺激对正常人内脏感觉中枢易化的作用

目的 利用功能磁共振成像(fMRI)技术观察食管酸灌注刺激相关内脏感觉中枢及活动特点.方法 采用改良组块设计模式对15名健康受试者进行食管酸(0.1 mmol/L HCI)或0.9%氯化钠溶液刺激,同时行fMRI.具体步骤为:静息期(A期)8 min,0.9%氯化钠溶液灌注(B期)8 min,酸灌注(C期)8 min,0.9%氯化钠溶液再灌注(D期)8 min,总时间为32 min.每个组块为160个时间点(scans),每个时间点为3 S,共采集640个时间点数据.观察受试者反应,并对受试者大脑功能区的改变进行统计学分析.结果 15名受试者中,10名刺激后出现咽喉部胀痛、烧心、胸痛等不适表现.初次0.9%氯化钠溶液刺激期(B-A)激活脑区包括中脑、前扣带回、左侧岛叶、两侧杏仁核及海马旁回、两侧前额皮质背外侧.酸灌注刺激期(C-A)及酸灌注后再灌注0.9%氯化钠溶液刺激期(D-A)所激活脑区与B-A期所激活脑区部位一致.同时发现,大部分激活部位强度逐渐增强,激活像素逐渐增多,即B-A期相似文献   

直肠内温度变化影响肠易激综合征患者内脏感觉阈值

目的 探讨直肠内温度及压力变化对肠易激综合征(IBS)患者内脏感觉阈值的影响，进一步研究IBS的发病机制。方法 通过直肠球囊内注入空气(压力刺激)、38℃温水、4℃冰水(温度刺激)及脐部放置冰袋加直肠球囊内充气，研究直肠温度和压力变化刺激对初始感觉阈值和排便阈值的影响。结果 (1)直肠球囊内注气后，IBS组患者的初始感觉阈值明显低于对照组，排便阈值差异不明显。IBS组中腹泻型与交替型患者的初始感觉阈值及排便阈值均明显降低；便秘型患者的初始感觉阈值稍低于对照组，排便阈值明显增高。(2)直肠球囊内注入4℃冰水后，除便秘型IBS的排便阈值稍有所增加外，其余患者初始感觉阈值及排便阈值均显著降低，以腹泻型变化最明显。(3)脐部放置冰袋可诱发部分患者产生症状，但对初始感觉阈值和排便阈值无明显影响。结论 直肠温度和压力刺激可明显降低IBS患者的初始感觉阈值和排便阈值，以腹泻型患者最显著。内脏对压力和温度的敏感性增高可能是IBS发病的重要机制之一。     

食管感觉与胃食管反流病

近年来,一些研究认为食管感觉敏感性改变可能在胃食管反流病发生中发挥着重要的作用.此文就食管高敏感表现,食管感觉的神经机制,食管感觉相关的神经递质及食管感觉与GERD等的研究进展作一综述.     

食管扩张刺激后兔食管内脏感觉改变及其中枢机制的实验研究

目的 探讨食管扩张刺激后兔食管内脏感觉改变及P物质(SP)、降钙素基因相关肽(CGRP)、5-羟色胺(5-HT)、Fos蛋白在中枢神经系统的作用.方法 新西兰白兔20只分为三组:食管扩张组(A组,n=8)和对照组(B组,n=6),分别给予0.9cm食管球囊扩张及假手术刺激,每次持续30 s,每日2次,共14 d,以及空白对照组(C组,n=6).采用动物行为学评分评价食管内脏感觉改变,免疫组化法观察幼兔食管下段黏膜、脊髓和脑组织中神经递质CGRP、SP、5-HT及Fos蛋白的表达.结果 动物食管机械扩张后,在行为学评分为1、2、3分时,A组球囊直径较B、C组明显减小(P＜0.05);A组食管、脊髓和延髓孤束核(NTS)的SP表达明显高于B、C组(P＜0.05),而B、C组间差异无统计学意义(P＞0.05);A组食管黏膜、脊髓、NTS、中脑导水管周围灰质(PAG)、丘脑的CGRP、Fos阳性细胞数较B、C组明显增多(P＜0.05);在食管和脊髓,A组5-HT的表达较B、C组显著升高(食管:27.67±3.27比11.00±1.79和11.17±1.33;脊髓24.00±5.22比11.33±2.94和11.83±2.48,P＜0.01),而在PAG,B组(17.67±2.07)和C组(16.83±2.32)5-HT的表达较A组(13.17±2.04)增多(P＜0.05).在脊髓,CGRP与Fos、SP与Fos、CGRP与SP有明显的相关性(相关系数分别为0.813、0.779、0.772,P值分别为0.025、0.034、0.036).结论 持续的食管扩张可引起食管内脏敏感性增高,食管的机械扩张刺激通过脊髓、NTS、PAG、丘脑传导,且SP、CGRP、5-HT等在食管内脏感觉发生中发挥着重要作用.     

糖尿病神经病变病人末梢感觉定量检查方法的探讨与临床应用

目的 探讨糖尿病(DM)病人末梢感觉定量检测方法(QST)及其在临床应用的价值。方法 采用计算机辅助感觉定量检查仪，检测120名正常人与92例DM病人四肢末梢的冷、热感觉，冷、热痛觉和振动觉等5项。结果 检测结果，临床常规检查有糖尿病神经病变(DPN)病人的检测数值100％异常，常规检查无神经病变的，与同时采用四肢末梢5项检测的数值比较，差异无显著意义(X^2-0．922，P=0．631)；DM病人QST检测结果与正常人数值比较，温度觉与振动觉明显减退；QST检查发现的DM末梢感觉异常人数比临床常规检查发现的明显增多(X^2=10．985，P=0．001)，这两种检查的异常人数又都与DM病程相关。结论 DM病人QST可选择足部作常规检查；计算机辅助感觉定量检测是早期发现DPN的良好指标。     

肠道促动力药物和内脏感觉调节剂

目前对功能性肠病的治疗不仅重视以症状为基础的治疗(如解痉剂、止泻剂,等),同时也更加重视肠道促动力药物的应用和对内脏感觉的调整.     

Effects of octreotide on esophageal visceral perception and cerebral evoked potentials induced by balloon distension

Objective: Octreotide, a somatostatin analog, is antinociceptive and increases perception threshold in the rectum. The aim of this study was to determine whether octreotide alters esophageal sensory thresholds and cortical evoked potentials (CEPs) resulting from intraesophageal balloon distension. Methods: Twelve healthy volunteers (six men and six women, median age 25 yr, range 21–60 yr) underwent a randomized, double-blind, placebo-controlled trial of octreotide 100 μg s.c. versus saline. A 30-mm balloon was inserted 5 cm above the lower esophageal sphincter without topical anesthesia. The balloon was inflated at a rate of 170 cc/s to a maximum of 30 cc in 2 cc steps. Both pressure and volume were recorded. Patients reported first sensation (S1) and maximally tolerated pain (S2). Two cycles were performed both preinjection and 40 min postinjection. Evoked potentials were recorded from Cz to linked ears over 50 balloon inflation cycles (volume = S2). Results: Threshold volume to first sensation (S1) was significantly increased after octreotide injection [median (interquartile range): 24 (14–26) cc vs 13 (9–21) cc,   p < 0.02  ]. No significant alteration in volume causing pain (S2) was noted after octreotide injection [29 (25–30+) cc vs 22 (19–29) cc]. Neither were volumes causing either first sensation [18 (11–24) cc vs 13 (9–18) cc] or pain [27 (23–30) cc vs 23 (21–25) cc] significantly altered by placebo injection. Neither amplitude nor latency of any of the three peaks of the evoked potential recordings differed significantly between postplacebo and postoctreotide recordings. Conclusion: Octreotide significantly increased esophageal perception thresholds to balloon distension. It did not alter pain thresholds, nor were cortical evoked potentials to painful stimulation altered in normal subjects.     

Colorectal visceral perception in diverticular disease

BACKGROUND AND AIMS: The pathogenesis of asymptomatic diverticular disease (ADD) and symptomatic uncomplicated diverticular disease (SUDD) has not been elucidated. The aim of our study was to assess whether altered visceral perception or abnormal compliance of the colorectal wall play a role in these clinical entities. METHODS: Ten ADD patients, 11 SUDD patients, and nine healthy controls were studied. Using a dual barostat device, sensations were scored and compliance curves obtained using stepwise intermittent isobaric distensions of the rectum and sigmoid, before and after a liquid meal. In addition, the colonic response to eating was assessed by monitoring the volumes of both barostat bags at operating pressure before and after the meal. RESULTS: In the rectum, perception was increased in the SUDD group compared with controls (p = 0.010) and the ADD group (p = 0.030). Rectal compliance curves were not different between the groups. In the sigmoid colon, perception in the pre- and postprandial periods was increased in SUDD compared with controls (p = 0.018) but not when compared with ADD. Sigmoid volume-pressure curves had comparable slopes (compliance) in all groups but were shifted downwards in SUDD compared with ADD in the preprandial period (p = 0.026). The colonic response to eating (decrease in intrabag volume) was similar in all three groups, both in the rectum and sigmoid. CONCLUSION: Symptomatic but not asymptomatic uncomplicated diverticular disease is associated with heightened perception of distension, not only in the diverticula bearing sigmoid, but also in the unaffected rectum. This hyperperception is not due to altered wall compliance.     

Persistently altered visceral perception after resection of an esophageal granular cell myoblastoma: a therapeutic concept revisited

Granular cell tumors (GCTs) are rare and usually benign gastrointestinal tumors. Their most frequent symptoms are dysphagia and epigastric or retrosternal discomfort. We here report a case of esophageal GCT with continued symptoms of retrosternal discomfort, postprandial feeling of fullness, and early satiety despite complete thoracoscopic resection of the tumor. In contrast, all functional tests were in the normal range. We thus suggest that, due to their neuroectodermal origin, GCTs may affect neuronal alterations leading to a persistently disturbed visceral mechanosensory perception. Consequently, this case also cautions the therapeutic concept to solely relieve GCT symptoms by resection if the tumor is less than 20 mm in diameter.     

食管内脏高敏感及其相关研究进展

胃食管反流疾病(gastroesophageal reflux disease,GERD)是一种较普遍的疾病,经常伴随各种不适症状,需要利用健康护理资源.在动物实验与人类实验研究中均表明,各种传入神经的受体在暴露于酸的情况下均可以敏感化,以至于使更多的感觉刺激通过传入神经输入到脊髓背角神经元,导致了这些神经元的阈值降低,使得他们的感受范围增大.这种敏感性增高的初级传入神经被形容为外周敏感化,而随之增加敏感性的脊髓背角神经元被描述为中央敏感化.一旦这些机制建立起来,可以使组织对以前原本无害的刺激发生敏感,并且会保持一个长期的过程.此外,心理压力和机械刺激都已经被证实可以使细胞间隙增宽,因此可能促进外围敏感化.目前,外围与中枢敏感化被认为是食管疼痛和高敏感的重要机制,甚至生理量的酸亦可以导致症状的发生.对于这些患者的治疗目的主要是降低神经的敏感性.本文主要围绕食管内脏感觉高敏感作一简要综述.     

Effects of nifedipine on esophageal tone and perception of esophageal distension

The effects of nifedipine (20 mg orally) on esophageal body resting tone and perception of esophageal distension were compared with those of placebo in 10 healthy volunteers, using a double-blind crossover design. A 3-cm silicon balloon positioned 10 cm above the lower esophageal sphincter was inflated with 2–20 ml of air, in 2-ml increments. The subjects scored their chest sensations, while pressure in the balloon was continuously recorded. In each experiment three series of measurements were made, at baseline and 15 and 30 min after administration of nifedipine or placebo. Bench tests were run to determine pressure-to-volume relationships for each of the balloons used in the study. Thirty minutes after nifedipine ingestion, a significant decrease in systolic blood pressure (from 112.6±2.3 to 99.0±2.0 mm Hg) was observed. Amplitude and duration of esophageal peristaltic contractions were significantly decreased by nifedipine (from 128.1±16.7 to 98.7±10.6 mm Hg and from 3.9±0.3 to 3.3±0.2 sec, respectively). With balloon volumes of 8 ml and higher, balloon pressures were higher with the balloon in the esophagus than on the bench, the difference being determined by the compliance of the esophagus. This difference rose from 18.5±6.8 to 40.2±7.2 mm Hg (8–20 ml) with placebo and from 23.1±3.7 to 35.9±5.8 mm Hg with nifedipine. No significant differences between nifedipine and placebo were found. The esophageal sensation scores increased linearly with increasing balloon volume from 6 ml onwards. Nifedipine had no significant effect on the perception of esophageal balloon distension.     

Symptoms and visceral perception in severe functional and organic dyspepsia

^a CURE: Digestive Disease Research Center/Neuroenteric Disease Program, UCLA, Los Angeles, California, USA, ^b Department of Medicine, Vanderbilt University, Nashville, Tennessee

Correspondence to: Dr E A Mayer, Neuroenteric Disease Program, West LA VA Medical Center, CURE Bldg 115, Rm 223, 11301 Wilshire Blvd, Los Angeles, California 90073, USA.

Accepted for publication 31 October 1997

Background—Hypersensitivity of gastric afferent pathways may play an aetiological role in symptoms of functional dyspepsia.
Aims—To determine whether patients with severe organic dyspepsia (associated with tissue irritation/injury) and those with functional dyspepsia (no detectable tissue irritation) differ in their perception of gastric distension and whether this difference is reflected in differences in their gastrointestinal and psychological symptoms.
Methods—Perceptual thresholds, referral patterns, and gastrointestinal and psychological symptoms were compared in 23 patients with functional dyspepsia, 10 organic dyspeptics, and 15 healthy controls.
Results—Fifteen (65%) functional dyspeptics and no organic dyspeptics had reduced perceptual thresholds for fullness, discomfort, or pain (odds ratio (OR) 19.56, 95% confidence interval (CI) 1.95 to 476.09, p=0.0017). Either reduced perceptual thresholds or altered referral was found in 20 (87%) functional dyspeptics and four (20%) organic dyspeptics (OR 10.0, 95% CI 1.34 to 89.54, p=0.014). During sham distension fullness, discomfort and pain were reported by healthy controls, organic dyspeptics, and functional dyspeptics. A sham response of pain but no other sensation was more frequent among functional dyspeptics (43%) than healthy controls (7%) (OR 10.77, 95% CI 1.10 to 257.35, p=0.026). Gastrointestinal and psychological symptoms and gastric compliance were similar in the functional and organic groups.
Conclusions—Alterations in the perception of gastric distension distinguishes between functional and organic dyspepsia, while symptoms do not. A total of 87% of functional dyspeptics studied had evidence of altered visceral afferent function. In this study population, psychological abnormalities or changes in compliance did not explain the findings.
(GUT 1998;:814-822)

Keywords: dyspepsia;  hyperalgesia;  visceral afferents

     

Visceral perception: sensory transduction in visceral afferents and nutrients

The possible mechanisms that may be involved in nutrient detection in the wall of the gastrointestinal tract are reviewed. There is strong functional and electrophysiological evidence that both intrinsic and extrinsic primary afferent neurones mediate mechano- and chemosensitive responses in the gastrointestinal tract. This review focuses on the extrinsic afferent pathways as these are the ones that convey information to the central nervous system which is clearly necessary for perception to occur.     

Sigmoid compliance and visceral perception in spinal cord injury patients

Intestinal motor and sensory dysfunctions in traumatic complete or incomplete spinal cord injury (SCI) are frequent and result in altered mechanisms of defecation. The aim of this study is to investigate sigmoid compliance and perception in chronic SCI patients. Sigmoid responses to fixed-tension distentions were assessed using a tensostat in six patients (six men, 42 ± 4 years) with chronic complete transection of the spinal cord (high-SCI; five tetraplegic C5-C7 and one paraplegic T4-T6) and impaired evacuation (i.e. constipation). A group of 10 healthy individuals (six men, 25 ± 1 years) served as controls. SCI patients had higher sigmoid compliance at the highest distention level than the controls (10.3 ± 2.4 vs. 5.1 ± 0.8 ml/mmHg; P<0.05). Perception scores at first sensation were higher in SCI patients (2.3 ± 0.7 vs. 1.1 ± 0.1; P<0.05), but were not different at the highest distention levels (3.7 ± 0.8 vs. 3 ± 1; NS). The most commonly reported sensation by patients was distention/bloating and was referred less commonly to the hypogastrium compared with distention/bloating in controls. An increased sigmoid compliance can be detected in constipated SCI patients. The preservation of some degree of visceral sensations, although abnormally referred, could imply the occurrence of sensory input remodeling at the spinal level.     

Symptoms and visceral perception in patients with pain-predominant irritable bowel syndrome

OBJECTIVE: Abdominal pain is thought to be a hallmark of the irritable bowel syndrome (IBS), although currently used symptom criteria do not differentiate between abdominal pain and discomfort. By focusing on viscerosensory symptoms, we sought to determine: 1) which type of symptoms are most commonly reported by IBS patients, and 2) whether patients who report pain as their most bothersome symptom differ in clinical, psychological, and physiological characteristics. METHODS: A total of 443 consecutive new patient referrals to a tertiary referral center for functional gastrointestinal disorders who met symptom criteria for IBS were given validated, psychometric, health status, and bowel symptom questionnaires containing specific questions regarding the patients' predominant viscerosensory gastrointestinal symptom. Of these patients, 155 (35%) also met criteria for functional dyspepsia. A representative subset of the total IBS patient population (n = 58) underwent evaluation of perceptual responses to controlled rectal distension before and after a noxious sigmoid conditioning stimulus. RESULTS: Viscerosensory symptoms clustered into four groups: 1) abdominal pain, 2) bloating-type discomfort, 3) sensation of incomplete rectal evacuation, and 4) extraabdominal (chest pain or pressure and nausea). A total of 66% of patients reported gas as one of their viscerosensory symptoms, whereas 60% reported abdominal pain as one of their symptoms. Only 29% rated abdominal pain as their most bothersome symptom, whereas bloating-type symptoms were listed by 60% as most bothersome. Although pain predominance did not correlate with the severity of gastrointestinal or psychological symptoms, there was a significant correlation with the development of rectal hypersensitivity in response to the sigmoid conditioning stimulus. CONCLUSIONS: In a tertiary referral population of IBS patients: 1) abdominal pain is reported by only one third of patients as their most bothersome viscerosensory symptoms; and 2) pain-predominance correlates with development of rectal hypersensitivity after a noxious sigmoid stimulus.