Adult zymosan re-exposure exacerbates the molecular alterations in the brainstem rostral ventromedial medulla of rats with early life zymosan-induced cystitis.

Recent evidence suggests that the descending modulatory pathways from the brainstem rostral ventromedial medulla (RVM) are important for bladder inflammatory pain. This study aimed to identify the long-term molecular changes in RVM neurons due to early life cystitis during neuronal development and the effect of reexposure later in adulthood. RVM tissues from two treatment protocols were used: (1) neonatal zymosan exposures with acute adult rechallenge (RC) and (2) only neonatal zymosan exposures (NRC).

Biomechanical increase in cervical esophageal wall tension during peristalsis.

During pharyngeal phase of swallowing, circumferential tension of the cervical esophagus (CTE) increases caused by a biomechanical process of laryngeal elevation pulling the cervical esophagus orad. The esophagus contracts longitudinally during esophageal peristalsis, therefore, we hypothesized that CTE increases during esophageal peristalsis by a biomechanical process. We investigated this hypothesis using 28 decerebrate cats instrumented with electromyographic (EMG) electrodes on the pharynx and esophagus, and esophageal manometry.

Biomechanical effects of esophageal elongation on the circumferential tension of the cervical esophagus in vivo.

Evidence obtained ex vivo suggests that physical elongation of the esophagus increases esophageal circumferential stress-strain ratio, but it is unknown whether this biomechanical effect alters esophageal function in vivo. We investigated the effects of physical or physiological elongation of the cervical esophagus on basal and active circumferential tension in vivo. The esophagus was elongated, using 29 decerebrate cats, either physically by distal physical extension of the esophagus or physiologically by stimulating the hypoglossal nerve, which activates laryngeal elevating muscles that elongate the esophagus.

A biomechanical response of the esophagus participates in swallowing.

Evidence suggests that a biomechanical process participates in esophageal function, but no such function has yet been identified. We investigated the role of a biomechanical process during swallowing in 30 decerebrate cats instrumented using electromyogram (EMG) electrodes, strain gauge force transducers, and manometry. We found that the cervical esophagus has a short-lasting circumferential tension response during the pharyngeal phase of swallowing (CTPP), and a concomitant EMG response.

Identification and characterization of rostral ventromedial medulla neurons synaptically connected to the urinary bladder afferents in female rats with or without neonatal cystitis.

The neurons in the rostral ventromedial medulla (RVM) play a major role in pain modulation. We have previously shown that early-life noxious bladder stimuli in rats resulted in an overall spinal GABAergic disinhibition and a long-lasting bladder/colon sensitization when tested in adulthood. However, the neuromolecular alterations within RVM neurons in the pathophysiology of early life bladder inflammation have not been elucidated.

Peripheral antinociceptive effects of a bifunctional μ and δ opioid receptor ligand in rat model of inflammatory bladder pain.

There is a need to develop a novel analgesic for pain associated with interstitial cystitis/painful bladder syndrome (IC/PBS). The use of the conventional μ-opioid receptor agonists to manage IC/PBS pain is controversial due to adverse CNS effects. These effects are attenuated in benzylideneoxymorphone (BOM), a low-efficacy μ-opioid receptor agonist/δ-opioid receptor antagonist that attenuates thermal pain and is devoid of reinforcing effects.

Characterization and mechanism of the esophago-esophageal contractile reflex of the striated muscle esophagus.

An esophago-esophageal contractile reflex (EECR) of the cervical esophagus has been identified in humans. The aim of this study was to characterize and determine the mechanisms of the EECR. Cats ( = 35) were decerebrated, electrodes were placed on pharynx and cervical esophagus, and esophageal motility was recorded using manometry.

Interplay of spinal and vagal pathways on esophageal acid-related anterior cingulate cortex functional networks in rats.

Esophageal acid sensory signals are transmitted by both vagal and spinal pathways to the cerebral cortex. The influence and interplay of these pathways on esophageal acid-related functional connectivity has been elusive. Our aim was to evaluate the esophageal acid exposure-related effect on the anterior cingulate cortex (ACC) functional connectivity networks using functional MRI-guided functional connectivity MRI (fcMRI) analysis.

Effects of esophageal acidification on esophageal reflexes controlling the upper esophageal sphincter.

Esophageal acid exposure can alter upper esophageal sphincter (UES) function, but the mechanism is unknown. The aim of this study was to determine the effects of esophageal acid exposure on esophago-UES relaxation (EURR) and contractile (EUCR) reflexes. Cats, decrebrate ( n = 27) or chronic ( n = 4), were implanted with electromyographic electrodes on pharynx, larynx, and esophagus.

The effect of body position on esophageal reflexes in cats: a possible mechanism of SIDS?

BackgroundIt has been hypothesized that life-threatening events are caused by supraesophageal reflux (SER) of gastric contents that activates laryngeal chemoreflex-stimulated apnea. Placing infants supine decreases the risk of sudden infant death syndrome (SIDS). The aim of this study was to determine whether body position affects esophageal reflexes that control SER.

MicroRNA-mediated downregulation of potassium-chloride-cotransporter and vesicular γ-aminobutyric acid transporter expression in spinal cord contributes to neonatal cystitis-induced visceral pain in rats.

Loss of GABAergic inhibition in pain pathways has been considered to be a key component in the development of chronic pain. In the present study, we intended to examine whether miR-92b-mediated posttranscriptional dysregulation of spinal potassium chloride cotransporter (KCC2) and vesicular γ-aminobutyric acid transporter (VGAT) plays a major role in the development and maintenance of long-term visceral hyperalgesia in neonatal zymosan-treated rats. Neonatal cystitis was induced by transurethral zymosan administration from postnatal (P) days 14 to 16 (protocol 1).

Characterization and mechanisms of the supragastric belch in the cat.

A response in which a belch occurs without gastric involvement, i.e., the supragastric belch (SGB), has been characterized in humans.

Characterization and mechanisms of the pharyngeal swallow activated by stimulation of the esophagus.

Stimulation of the esophagus activates the pharyngeal swallow response (EPSR) in human infants and animals. The aims of this study were to characterize the stimulus and response of the EPSR and to determine the function and mechanisms generating the EPSR. Studies were conducted in 46 decerebrate cats in which pharyngeal, laryngeal, and esophageal motility was monitored using EMG, strain gauges, or manometry.

Prolonged esophageal acid exposures induce synaptic downscaling of cortical membrane AMPA receptor subunits in rats.

Background: We recently reported the involvement of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor subunit upregulation and phosphorylation in the rostral cingulate cortex (rCC) as the underlying mechanism of acute esophageal acid-induced cortical sensitization. Based on these findings, we proposed to investigate whether prolonged esophageal acid exposures in rats exhibit homeostatic synaptic scaling through downregulation of AMPA receptor expression in rCC neurons. We intended to study further whether this compensatory mechanism is impaired when rats are pre-exposed to repeated esophageal acid exposures neonatally during neuronal development.

Mechanisms of airway responses to esophageal acidification in cats.

Acid in the esophagus causes airway constriction, tracheobronchial mucous secretion, and a decrease in tracheal mucociliary transport rate. This study was designed to investigate the neuropharmacological mechanisms controlling these responses. In chloralose-anesthetized cats (n = 72), we investigated the effects of vagotomy or atropine (100 μg·kg(-1)·30 min(-1) iv) on airway responses to esophageal infusion of 0.

Mechanism of UES relaxation initiated by gastric air distension.

The aim of this study was to determine the mechanism of initiation of transient upper esophageal sphincter relaxation (TUESR) caused by gastric air distension. Cats (n = 31) were decerebrated, EMG electrodes were placed on the cricopharyngeus, a gastric fistula was formed, and a strain gauge was sewn on the lower esophageal sphincter (n = 8). Injection of air (114 ± 13 ml) in the stomach caused TUESR (n = 18) and transient lower esophageal sphincter relaxation (TLESR, n = 6), and this effect was not significantly (P > 0.

Role of peripheral reflexes in the initiation of the esophageal phase of swallowing.

The aim of this study was to determine the role of peripheral reflexes in initiation of the esophageal phase of swallowing. In 10 decerebrate cats, we recorded electromyographic responses from the pharynx, larynx, and esophagus and manometric data from the esophagus. Water (1-5 ml) was injected into the nasopharynx to stimulate swallowing, and the timing of the pharyngeal and esophageal phases of swallowing was quantified.

AMPA receptor subunits expression and phosphorylation in cingulate cortex in rats following esophageal acid exposure.

Background: We recently reported an increase in N-methyl-d-aspartate (NMDA) receptor subunit expression and CaMKII-dependent phosphorylation of NR2B in the rostral cingulate cortical (rCC) neurons following esophageal acid exposure in rats. As α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors mediate the fast excitatory transmission and play a critical role in synaptic plasticity, in this study, we investigated the effect of esophageal acid exposure in rats on the expression of AMPA receptor subunits and the involvement of these molecular alterations in acid-induced sensitization of neurons in the anterior cingulate (ACC) and midcingulate (MCC) cortices.

Methods: In molecular study, we examined GluA1 and GluA2 expression and phosphorylation in membrane preparations and in the isolated postsynaptic densities (PSDs) from rats receiving acute esophageal exposure of either saline (control group) or 0.

Digestive and respiratory tract motor responses associated with eructation.

We studied the digestive and respiratory tract motor responses in 10 chronically instrumented dogs during eructation activated after feeding. Muscles were recorded from the cervical area, thorax, and abdomen. The striated muscles were recorded using EMG and the smooth muscles using strain gauges.

The role of the superior laryngeal nerve in esophageal reflexes.

The aim of this study was to determine the role of the superior laryngeal nerve (SLN) in the following esophageal reflexes: esophago-upper esophageal sphincter (UES) contractile reflex (EUCR), esophago-lower esophageal sphincter (LES) relaxation reflex (ELIR), secondary peristalsis, pharyngeal swallowing, and belch. Cats (N = 43) were decerebrated and instrumented to record EMG of the cricopharyngeus, thyrohyoideus, geniohyoideus, and cricothyroideus; esophageal pressure; and motility of LES. Reflexes were activated by stimulation of the esophagus via slow balloon or rapid air distension at 1 to 16 cm distal to the UES.

Neuronal plasticity in the cingulate cortex of rats following esophageal acid exposure in early life.

Background & Aims: The cingulate cortex has been reported to be involved in processing pain of esophageal origin. However, little is known about molecular changes and cortical activation that arise from early-life esophageal acid reflux. Excitatory neurotransmission via activation of the N-methyl-d-aspartate (NMDA) receptor and its interaction with postsynaptic density protein 95 (PSD-95) at the synapse appear to mediate neuronal development and plasticity.

Differential activation of medullary vagal nuclei caused by stimulation of different esophageal mechanoreceptors.

Esophageal mechanoreceptors, i.e. muscular slowly adapting tension receptors and mucosal rapidly adapting touch receptors, mediate different sets of reflexes.

Differential activation of pontomedullary nuclei by acid perfusion of different regions of the esophagus.

The objective of this study was to determine the brain stem nuclei and physiological responses activated by esophageal acidification. The effects of perfusion of the cervical (ESOc), or thoracic (ESOt) esophagus with PBS or HCl on c-fos immunoreactivity of the brain stem or on physiological variables, and the effects of vagotomy were examined in anesthetized cats. We found that acidification of the ESOc increased the number of c-fos positive neurons in the area postrema (AP), vestibular nucleus (VN), parabrachial nucleus (PBN), nucleus ambiguus (NA), dorsal motor nucleus (DMN), and all subnuclei of the nucleus tractus solitarius (NTS), but one.

Altered expression of P2X3 in vagal and spinal afferents following esophagitis in rats.

Purinergic P2X(3) receptors are predominantly expressed in small diameter primary afferent neurons and activation of these receptors by adenosine triphosphate is reported to play an important role in nociceptive signaling. The objective of this study was to investigate the expression of P2X(3) receptors in spinal and vagal sensory neurons and esophageal tissues following esophagitis in rats. Two groups of rats were used including 7 days fundus-ligated (7D-ligated) esophagitis and sham-operated controls.

Altered mechanosensitive properties of vagal afferent fibers innervating the stomach following gastric surgery in rats.

Background And Aims: Several types of gastric surgeries have been associated with early satiety, dyspepsia and food intolerances. We aimed to examine alterations in gastric vagal afferents following gastric surgery-fundus ligation.

Methods: Six week old, male Sprague-Dawley rats underwent chronic ligation (CL) of the fundus.