Central serotonergic and noradrenergic receptors in functional dyspepsia

Functional dyspepsia is a symptom complex characterised by upper abdominal discomfort or pain, early satiety, motor abnormalities, abdominal bloating and nausea in the absence of organic disease. The central nervous system plays an important role in the conducting and processing of visceral signals. Alterations in brain processing of pain, perception and affective responses may be key factors in the pathogenesis of functional dyspepsia. Central serotonergic and noradrenergic receptor systems are involved in the processing of motor, sensory and secretory activities of the gastrointestinal tract. Visceral hypersensitivity is currently regarded as the mechanism responsible for both motor alterations and abdominal pain in functional dyspepsia. Some studies suggest that there are alterations in central serotonergic and noradrenergic systems which may partially explain some of the symptoms of functional dyspepsia. Alterations in the autonomic nervous system may be implicated in the motor abnormalities and increases in visceral sensitivity in these patients. Noradrenaline is the main neurotransmitter in the sympathetic nervous system and again alterations in the functioning of this system may lead to changes in motor function. Functional dyspepsia causes considerable burden on the patient and society. The pathophysiology of functional dyspepsia is not fully understood but alterations in central processing by the serotonergic and noradrenergic systems may provide plausible explanations for at least some of the symptoms and offer possible treatment targets for the future.     

Sphincter of Oddi dysfunction and unexplained abdominal pain: Clinical and manometric study

Unexplained, biliary-type abdominal pain is often attributed to an abnormal pressure profile of the sphincter of Oddi. In spite of this assumption, the true prevalence of this type of motor dysfunction among cholecystectomized patients with unexplained abdominal pain is not known. We studied 64 postcholecystectomy patients who were thought to have sphincter of Oddi dysfunction. Radiologically, other than a dilated common bile duct in some, they had no anatomic derangement of their pancreatobiliary tract to explain their symptoms. They were categorized into three groups on the basis of four objective findings suggesting abnormal biliary emptying mechanism. Basal sphincter of Oddi pressure, frequency of phasic contractions, and proportion of retrograde contractions were determined in all patients. Twenty-six (41%) of the patients demonstrated at least one motor abnormality, 16 (25%) had two, and 10 (16%) had all three abnormal parameters. The pressure profile of the sphincter was normal in 38 or 59% of the patients. Seventy-three percent (73%) of the patients in group I, who had three or four of the objective findings for sphincter of Oddi dysfunction, demonstrated at least one motor abnormality. Sixty percent of this group demonstrated an increased basal sphincter of Oddi pressure. On the other hand, only 19% of the patients in group III, who had none of the objective findings, revealed a motor abnormality. Increased basal sphincter of Oddi pressure was noted in 7% of this group. We conclude that, sphincter of Oddi dysfunction, as diagnosed manometrically, explains the recurrent biliary type abdominal pain in a minority of patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recurrent spinal cord ischemia due to abdominal aortic aneurysm--a case report

Ischemic spinal cord lesions with abdominal aortic aneurysm are rare and are usually characterized by a single catastrophic event. The authors report a seventy-five-year-old woman who, over a period of three years, had three attacks of acute neurologic deficit. The clinical features were those of bladder incontinence, a mixture of upper and lower motor neuron lower limb motor deficit, and patchy sensory loss with a sensory level at T10-12. Investigations revealed a large abdominal aortic aneurysm that had enlarged with time. This case, they believe, represents an example of recurrent ischemic myelopathy due to occlusion at the mouth of radicular arteries or recurrent embolic events in those vessels.     

Aortic rupture as a result of a sporting injury.

Blunt abdominal aortic rupture is a rare and almost invariably fatal injury that usually occurs as a consequence of motor vehicle accidents. The case of a patient who sustained a nonfatal abdominal aortic rupture while playing soccer is reported. This is the third nonfatal case to be described and the first as the result of a sporting injury.     

Esophageal stimulation tests

Both pharmacological and mechanical stimulation tests are used to evaluate the motor function of the esophagus and its sphincters. The stimulation of the esophagus allows not only evaluation of basal motor parameters but gives also information about the capability of the organ to respond to defined stimuli. Pentagastrin and edrophonium have been used to stimulate the esophageal motor function mainly with the intension of revealing abnormal motility patterns. In the esophageal body, the administration of the compounds allows detection of motor abnormalities. In contrast to a pharmacological stimulation test, the response of the lower esophageal sphincter to mechanical stimulation with an increase in abdominal pressure-applied by leg raising or using an abdominal beltremains a controversials field. The conflict is due to the fact that some investigators postulate an atropine-sensitive or vagally mediated reflex, whereas others suggest a purely mechanical extrinsic compression of the intraabdominal portion of the esophagus. The latter explanation seems to be wrong due to the fact that during mechanical stimulation with intermittend abdominal compression the change in pressure in the LES exceeds the time of the mechanical stimulation. The results were obtained in healthy persons and in patients with different esophageal motility disorders. It was concluded, therefore, that an increase in abdominal pressure results in an adaptive pressure rise in the LES, which can be used to evaluate the lower esophageal sphincter in a more detailed and functional way. In the esophageal body abnormal motility patterns can be more distinctly provoked by inducing swallowing with a defined bolus. Wet swallows more frequently allow detection of esophageal motor dysfunction than dry swallows. The inflation of a balloon in the esophageal body is sometimes helpful in patients with noncardiac chest pain to correlate mechanical stress with esophageal related symptoms.     

Jejunal Manometry Predicts Tube Feeding Intolerance in the Postoperative Period

Postoperative nutrition is best provided enterally; however, patients often develop intolerance to enteral feedings. Our aim was to prospectively identify abdominal examination and jejunal pressure activity associated with postoperative intolerance of enteral feedings. Twenty-nine patients underwent abdominal operation and needle catheter jejunostomy placement. Elemental tube feedings were started on the day after surgery and advanced to the caloric goal rate over three days. Patients whose feedings were slowed at the attending surgeon's discretion were defined as intolerant. Jejunal manometry and a standardized abdominal exam were performed on postoperative days 1, 3, and 5. Fifteen patients (52%) were intolerant of tube feedings and had decreased jejunal motor activity but more active bowel sounds prior to feedings. After feedings, intolerant patients developed abdominal distension, but other abdominal findings were inconsistent. A marked decrease in phase II of the migrating motility complex (MMC) and the lack of a fed response were present in both groups. The overall jejunal motility present on day 1 following surgery identifies patients that will not tolerate enteral feedings. The abdominal examination, MMC parameters, and motor response to feeding did not predict feeding intolerance.     

Motility disorders in childhood

Motility disorders are very common in childhood, causing a number of gastrointestinal symptoms: recurrent vomiting, abdominal pain and distension, constipation and obstipation, and loose stools. The disorders result from disturbances of gut motor control mechanisms caused by either intrinsic disease of nerve and muscle, central nervous system dysfunction or perturbation of the humoral environment in which they operate. Intrinsic gut motor disease and central nervous system disorder are most usually congenital in origin, and alterations of the humoral environment acquired. Irritable bowel syndrome occurs in children as well as adults and is multifactorial in origin, with an interplay of psychogenic and organic disorders.     

Chemical nociception in the jejunum induced by capsaicin

BACKGROUND AND AIMS: Chemonociception in the human small intestine has not been studied extensively. Although capsaicin can cause intestinal sensations, it is not known if this is due to stimulation of chemoreceptors or to motor changes. Our aims were to evaluate motor activity during capsaicin induced nociception and to compare qualities of jejunal nociception induced by capsaicin and mechanical distension. METHODS: Twenty nine healthy subjects swallowed a tube with a perfusion site at the ligament of Treitz and, 7 cm distally, a barostat balloon. Phasic motor activity was measured around the perfusion site and the balloon. Capsaicin solutions (40, 200, and 400 microg/ml) 2.5 ml/min were perfused for 60 minutes or until severe discomfort occurred. A graded questionnaire for seven different sensations was completed every 10 minutes and after capsaicin perfusion was replaced by saline perfusion because of severe discomfort. Sensations arising from pressure controlled distensions were assessed before and after capsaicin perfusion when sensations had stopped (n = 19), or during capsaicin administration when no discomfort was reported (n = 5). RESULTS: Capsaicin perfusion induced feelings of pressure, cramps, pain, and warmth. The quality and abdominal location of these sensations were similar to those induced by distension, except for warmth (p<0.01) and pressure (p<0.05). Seven of 12 subjects receiving 40 microg/ml capsaicin and all subjects receiving higher capsaicin concentrations developed discomfort. Perfusion had to be stopped after 55 (3.3), 15 (5.7), and 10 (2.2) minutes with 40, 200, and 400 microg/ml capsaicin, respectively, whereafter the sensations disappeared within 10 minutes. Repeated capsaicin (200 microg/ml) applications significantly reduced the time until discomfort occurred (p = 0.01). Jejunal tone was not altered by capsaicin but phasic activity proximal to the perfusion site was reduced during capsaicin induced discomfort (p<0.001). Pain thresholds during distensions were not different before and after capsaicin perfusion. CONCLUSION: Despite the similarities in abdominal localisation and perceptional quality of capsaicin and distension induced sensations, our results rule out the fact that abdominal discomfort evoked by capsaicin involves sensitisation of mechanoreceptors or an increase in phasic and tonic motor activity. Capsaicin evokes abdominal sensations by stimulation of chemoreceptors which proves the existence of chemonociception in the human small intestine.     

Neuroimmune mechanisms in functional bowel disorders

The enteric nervous system regulates diverse functions including gastrointestinal motility and nociception. The sensory neurons detect mechanical and chemical stimuli while motor neurons control peristalsis and secretion. In addition to this extensive neuronal network, the gut also houses a highly specialised immune system which plays an important role in the induction and maintenance of tolerance to food and other luminal antigens and in the protection of the epithelial barrier against pathogenic invasion. It is now increasingly recognised that the gastrointestinal immune system and the enteric nervous system closely interact. This review will focus on two common functional gastrointestinal disorders in which neuroimmune interaction is involved in the pathophysiology: i.e. postoperative ileus and irritable bowel syndrome. Postoperative ileus arises after almost every abdominal surgical procedure. Handling of the bowel results in local inflammation and activation of inhibitory neuronal pathways resulting in a generalised impairment of gastrointestinal motor function or ileus. On the other hand, postinfectious irritable bowel syndrome (PI-IBS) occurs in 10 to 30% of patients who suffer from infectious gastroenteritis. PI -IBS patients develop abnormal gastrointestinal sensitivity, motility and secretion which contribute to abdominal pain and discomfort, bloating and abnormal bowel function (diarrhoea and/or constipation). Biopsy studies revealed persistent low-grade inflammation and altered immunological function which may lead to abnormal pain perception and motor activity within the gastrointestinal tract.     

Role of visceral afferent mechanisms in functional bowel disorders

This report analyzes the clinical and physiological evidence supporting a role for altered visceral afferent mechanisms in the pathogenesis of two functional bowel syndromes: noncardiac chest pain and the irritable bowel syndrome. Considerable recent evidence indicates that increased contractility is present only in a minority of patients and that hypercontractile episodes are not temporally related to abdominal pain. In contrast, altered sensation and motor reflexes in response to physiological stimuli, such as mechanical distention or acid, is common when appropriately investigated. The vagal and spinal afferent innervation mediates visceral sensation and is involved in multiple reflex loops regulating gastrointestinal effector function, such as motility and secretion. Sensory input can be modulated peripherally at the afferent nerve terminal, at the level of prevertebral ganglia, the spinal cord, and the brainstem. An up-regulation of afferent mechanisms would result both in altered conscious perception of physiological stimuli and in altered motor reflexes. Current evidence is consistent with an alteration in the peripheral functioning of visceral afferents and/or in the central processing of afferent information in the etiology of altered somatovisceral sensation and motor function observed in patients with functional bowel disease.     

Colonic Motor Function in Humans Is Not Affected by Gender

Functional abdominal pain, including the irritable bowel syndrome, is more common in females. Our aim was to determine if differences in motility or biomechanical properties of the colon could account for this gender difference. In 18 healthy subjects (nine males), a catheter assembly incorporating a balloon and perfused side holes, connected to a barostat, was positioned in the left colon. The system was used to determine compliance, sensation in response to phasic balloon distension, and changes in motor activity and tone in response to a meal. There was no significant difference in any of these variables between males and females. We conclude that there is no gender difference in colonic motor function or sensation to balloon distension. The increased prevalence of irritable bowel syndrome in females may be related to psychosocial factors rather than differences in colonic motor function.     

Influence of phasic volume feedback on abdominal expiratory nerve activity

Our purpose was to examine the influence of phasic lung volume feedback on the activities of motor nerves innervating the diaphragm and transversus abdominis muscles during hypercapnia and hypoxia. We studied seventeen decerebrate cats that were paralyzed and ventilated with a servo-respirator controlled by the integrated phrenic neurogram. The effects of phasic lung volume feedback were assessed by withholding pulmonary inflation during the central inspiratory period. Withholding lung inflation for a single respiratory cycle under hyperoxic, normocapnic conditions consistently prolonged the durations of the inspiratory and expiratory periods, and caused marked increases in the peak electrical activities of both phrenic and abdominal nerves. Hyperoxic hypercapnia (PaCO2 50-80 mmHg) and isocapnic hypoxia (PaO2 60-35 mmHg) increased peak phrenic and abdominal neural activities, and withholding pulmonary inflation under these conditions caused even greater augmentations of inspiratory and expiratory motor output. The augmentation of expiratory activity by withholding lung inflation was proportionately greater than the concomitant prolongation of the central expiratory period. All responses to non-inflation maneuvers were abolished following bilateral cervical vagotomy. The results indicate that vagally mediated volume feedback during inspiration can attenuate the output of abdominal motoneurons in the subsequent expiratory period. Moreover, hypoxia, which attenuates abdominal motor activity in vagotomized animals, enhances this activity when the vagi are intact.     

Influence of H. pylori Infection on Gastric Motor and Sensory Function in Asymptomatic Volunteers

The effect of H. pylori infection on gastricmotility and sensation is unclear. Our hypothesis isthat H. pylori infection increases gastric sensation andreduces gastric accommodation and emptying. In eight H. pylori-positive and eight H.pylori-negative asymptomatic subjects, infection wasproven by antral histology or culture. We evaluated: (1)gastric emptying of solids, (2) proximal gastriccompliance, (3) fasting and postprandial proximal gastrictone and phasic contractions, (4) gastric sensationduring balloon inflations or ingestion of cold water,and (5) abdominal vagal function. H. pylori infection was associated with lower gastric accommodation(median 75% postprandial increase in barostat balloonvolume compared to fasting) when compared to theaccommodation in uninfected volunteers (median 211% change from fasting). One H. pylori-positivesubject had an abnormal abdominal vagal function testand her gastric accommodation response was reduced.Other motor and sensory functions in the two groups were similar. In asymptomatic volunteers, H.pylori infection and gastritis result in reducedaccommodation (diastolic dysfunction) but no change inoverall sensation or motor functions of thestomach.     

Reassessment of functional dyspepsia： A topic review

Dyspepsia itself is not a diagnosis but stands for a constellation of symptoms referable to the upper gastrointestinal tract. It consists of a variable combination of symptoms including abdominal pain or discomfort, postprandial fullness, abdominal bloating, early satiety, nausea, vomiting, heartburn and acid regurgitation. Patients with heartburn and acid regurgitation invariably have gastroesophageal reflux disease and should be distinguished from those with dyspepsia. There is a substantial group of patients who do not have a definite structural or biochemical cause for their symptoms and are considered to be suffering from functional dyspepsia (FD). Gastrointestinal motor abnormalities, altered visceral sensation, dysfunctional central nervous system-enteral nervous system (CNS-ENS) integration and psychosocial factors have all being identified as important pathophysiological correlates. It can be considered as a biopsychosocial disorder with dysregulation of the brain-gut axis being central in origin of disease. FD can be categorized into different subgroups based on the predominant single symptom identified by the patient. This subgroup classification can assist us in deciding the appropriate symptomatic treatment for the patient.     

Altered small bowel motility in irritable bowel syndrome is correlated with symptoms

The pathogenesis of irritable bowel syndrome (IBS) has been related more to dysmotility of the colon than to abnormalities of the small intestine. To look for small bowel abnormalities, we recorded ultraluminal pressures in 16 patients with IBS. All patients complained of abdominal pain, and diarrhea (n = 8) or constipation (n = 8) were also prominent symptoms. Comparable studies were performed on 16 age-matched controls. The observations include diurnal and nocturnal fasting recordings and the response to a fatty meal. Periodicities of the interdigestive migrating myoelectric complexes were shorter in IBS (p less than 0.05); this was due to much shorter diurnal cycles in patients with diarrhea (77 +/- 10 min) than those with constipation (118 +/- 15 min) or controls (113 +/- 10 min, both p less than 0.05). All groups exhibited circadian changes, with nocturnal cycles being more frequent. Two specific patterns of small bowel motor activity were more common in IBS--ileal propulsive waves and clusters of jejunal pressure activity (both p less than 0.05 compared to controls). Moreover, cramping abdominal pain was usually noted in IBS when ileal motility was propulsive; jejunal bursts were also sometimes associated with abdominal symptoms. We conclude that motility of the small intestine is modified in some patients with IBS and that certain motor patterns are related to their symptoms.     

Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury

The cytokine erythropoietin (EPO) possesses potent neuroprotective activity against a variety of potential brain injuries, including transient ischemia and reperfusion. It is currently unknown whether EPO will also ameliorate spinal cord injury. Immunocytochemistry performed using human spinal cord sections showed abundant EPO receptor immunoreactivity of capillaries, especially in white matter, and motor neurons within the ventral horn. We used a transient global spinal ischemia model in rabbits to test whether exogenous EPO can cross the blood-spinal cord barrier and protect these motor neurons. Spinal cord ischemia was produced in rabbits by occlusion of the abdominal aorta for 20 min, followed by saline or recombinant human (rHu)-EPO (350, 800, or 1,000 units/kg of body weight) administered intravenously immediately after the onset of reperfusion. The functional neurological status of animals was better for rHu-EPO-treated animals 1 h after recovery from anesthesia, and improved dramatically over the next 48 h. In contrast, saline-treated animals exhibited a poorer neurological score at 1 h and did not significantly improve. Histopathological examination of the affected spinal cord revealed widespread motor neuron injury associated with positive terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling in control but not in rHu-EPO-treated animals. These observations suggest both an acute as well as a delayed beneficial action of rHu-EPO in ischemic spinal cord injury. Because rHu-EPO is currently used widely with an excellent safety profile, clinical trials evaluating its potential to prevent motor neuron apoptosis and the neurological deficits that occur as a consequence of ischemic injury are warranted.     

Blunt trauma to the infrarenal abdominal aorta with neurologic lesions. Case report and review of the literature

We report the case of a 31-year-old female involved in a severe motor vehicle accident. The diagnosis of blunt trauma to the abdominal aorta was not retained initially. The patient was referred to our institution when she developed a delayed paralysis of the lower limbs associated with the disappearance of both femoral pulses. Computed tomography evidenced dissection of the infrarenal aorta and NMR ruled out injury to the spinal cord. An aortoiliac endarteriectomy was then performed. Neurological recovery was partial at 3 months. We reviewed the frequency, the mechanisms and the management of blunt trauma to the abdominal aorta.     

Management of gastroparesis

Gastroparesis presents with nausea, vomiting, early satiety and abdominal discomfort, as well as a range of nongastrointestinal manifestations in association with delays in gastric emptying. The disorder may be a consequence of systemic illnesses, such as diabetes mellitus, occur as a complication of gastroesophageal surgery or develop in an idiopathic fashion and may mimic other disorders with normal gastric emptying. Some cases of idiopathic gastroparesis present after a viral infection. Management relies primarily on therapies that accelerate gastric emptying or reduce vomiting, although endoscopic or surgical options are available for refractory cases. Current research is focusing on the cellular and molecular mechanisms underlying development of delayed gastric emptying, as well as factors unrelated to motor dysfunction that may elicit some symptoms. Future pharmaceuticals will target the contractile and nonmotor defects via novel pathways. Novel electrical stimulation techniques will be employed either alone or in combination with medications.     

Surgical management of failed esophagomyotomy (Heller's operation).

An analysis of the causes of failure of Heller's operation is necessary in order to arrive at appropriate treatment. We retrospectively studied 100 reoperations for failed esophagomyotomy. Usually, a repeat myotomy was performed via an abdominal approach if the initial Heller's operation proved a failure, or via a thoracic approach if extensive motor disorders were discovered at manometry. Until 1978, esophagogastric resections were performed for severe esophageal injuries due to reflux after Heller's operation, but since then, duodenal diversion has obviated the need for resection. Antrectomy with Roux-en-Y gastrojejunostomy and vagotomy might be performed via an abdominal approach because the latter, always mandatory, is feasible through a transdiaphragmatic approach. Esophageal resection was reserved for major esophageal asystole, some cases of sclerosis, and carcinomas occurring or discovered after Heller's operation.     

Functional dyspepsia: recent pathophysiological advances

Functional dyspepsia is a clinical syndrome defined by upper abdominal symptoms, without identifiable cause by conventional diagnostic evaluation. New diagnostic tests, such as gastrointestinal manometry and gastric emptying, may help in a better characterization of these patients by demonstrating specific motor abnormalities, such as postprandial antral hypomotility and delayed gastric emptying of solids, or less frequently, intestinal dysmotility patterns indicating a visceral neuropathy. Nevertheless, a substantial proportion of dyspeptic patients have normal motility patterns. Interestingly, recent studies have shown that a gastric hypersensitivity to distension may be the cause of the postprandial symptoms in functional dyspepsia. These data indicate that functional dyspepsia may include an heterogeneous group of patients with different underlying disturbances.