Impaired adaptation of gastrointestinal motility following chronic stress in maternally separated rats.

Exposure to early life stress causes increased stress responsiveness and permanent changes in the central nervous system. We recently showed that delayed gastric emptying (GE) and accelerated colonic transit (CT) in response to acute restraint stress (ARS) were completely restored following chronic homotypic stress (CHS) in rats via upregulation of hypothalamic oxytocin (OXT) expression. However, it is unknown whether early life stress affects hypothalamic OXT circuits and gastrointestinal motor function. Neonatal rats were subjected to maternal separation (MS) for 180 min/day for 2 wk. Anxiety-like behaviors were evaluated by the elevated-plus-maze test. GE and CT were measured under nonstressed (NS), ARS, and CHS conditions. Expression of corticotropin-releasing factor (CRF) and OXT in the paraventricular nucleus (PVN) of the hypothalamus was evaluated by real time RT-PCR and immunohistochemistry. MS increased anxiety-like behaviors. ARS delayed GE and accelerated CT in control and MS rats. After CHS, delayed GE and accelerated CT were restored in control, but not MS, rats. CRF mRNA expression was significantly increased in response to ARS in control and MS rats. Increased CRF mRNA expression was still observed following CHS in MS, but not control, rats. In response to CHS, OXT mRNA expression was significantly increased in control, but not MS, rats. The number of OXT-immunoreactive cells was increased following CHS in the magnocellular part of the PVN in control, but not MS, rats. MS impairs the adaptation response of gastrointestinal motility following CHS. The mechanism of the impaired adaptation involves downregulation of OXT and upregulation of CRF in the hypothalamus in MS rats.

Hypothalamic circuit regulating colonic transit following chronic stress in rats.

Although acute stress accelerates colonic transit, the effect of chronic stress on colonic transit remains unclear. In this study, rats received repeated restraint stress (chronic homotypic stress) or various types of stress (chronic heterotypic stress) for 5 and 7 days, respectively. Vehicle saline, oxytocin (OXT), OXT receptor antagonist or corticotropin-releasing factor (CRF) receptor antagonists were administered by intracerebroventricular (ICV) injection prior to restraint stress for 90 min. Immediately after the stress exposure, the entire colon was removed and the geometric center (GC) of Na51CrO4 (a nonabsorbable radioactive marker; 0.5 µCi) distribution was calculated to measure the transit. Gene expression of OXT and CRF in the paraventricular nucleus (PVN) was evaluated by in situ hybridization. Accelerated colonic transit with the acute stressor was no longer observed following chronic homotypic stress. This restored colonic transit was reversed by ICV injection of an OXT antagonist. In contrast, chronic heterotypic stress significantly accelerated colonic transit, which was attenuated by ICV injection of OXT and by a CRF receptor 1 antagonist. OXT mRNA expression in the PVN was significantly increased following chronic homotypic stress, but not chronic heterotypic stress. However, CRF mRNA expression in the PVN was significantly increased following acute and chronic heterotypic stress, but not chronic homotypic stress. These results indicate that central OXT and CRF play a pivotal role in mediating the colonic dysmotility following chronic stress in rats.

Anti-stress effects of transcutaneous electrical nerve stimulation (TENS) on colonic motility in rats.

BACKGROUND: Disorders of colonic motility may contribute to symptoms in patients with irritable bowel syndrome (IBS), and stress is widely believed to play a major role in developing IBS. Stress increases corticotropin releasing factor (CRF) of the hypothalamus, resulting in acceleration of colonic transit in rodents. In contrast, hypothalamic oxytocin (OXT) has an anti-stress effect via inhibiting CRF expression and hypothalamic-pituitary-adrenal axis activity. Although transcutaneous electrical nerve stimulation (TENS) and acupuncture have been shown to have anti-stress effects, the mechanism of the beneficial effects remains unknown. AIMS: We tested the hypothesis that TENS upregulates hypothalamic OXT expression resulting in reduced CRF expression and restoration of colonic dysmotility in response to chronic stress. METHODS: Male SD rats received different types of stressors for seven consecutive days (chronic heterotypic stress). TENS was applied to the bilateral hind limbs every other day before stress loading. Another group of rats did not receive TENS treatment. RESULTS: TENS significantly attenuated accelerated colonic transit induced by chronic heterotypic stress, which was antagonized by a central injection of an OXT antagonist. Immunohistochemical study showed that TENS increased OXT expression and decreased CRF expression at the paraventricular nucleus (PVN) following chronic heterotypic stress. CONCLUSIONS: It is suggested that TENS upregulates hypothalamic OXT expression which acts as an anti-stressor agent and mediates restored colonic dysmotility following chronic stress. TENS may be useful to treat gastrointestinal symptoms associated with stress.

The role of 5-HT3 and 5-HT4 receptors in the adaptive mechanism of colonic transit following the parasympathetic denervation in rats.

BACKGROUND: Clinical studies show that disturbed colonic motility induced by extrinsic nerves damage is restored over time. We studied whether 5-HT3 and 5HT4 receptors are involved in mediating the adaptive mechanisms following parasympathetic denervation. METHODS: Parasympathetic denervation of the entire colon was achieved by bilateral pelvic nerve transection and truncal vagotomy in rats. Colonic transit was measured by calculating the geometric center (GC) of 51Cr distribution. Expression of 5-HT3 and 5HT4 receptor mRNA was determined by real time RT-PCR. RESULTS: Parasympathetic denervation caused a significant delay in colonic transit (GC=4.36) at postoperative day (POD) 1, compared with sham operation (GC=6.31). Delayed transit was gradually restored by POD 7 (GC=5.99) after the denervation. Restored colonic transit was antagonized by the administration of 5-HT3 and 5HT4 receptors antagonists at POD 7. 5-HT3 and 5HT4 receptors mRNA expression were significantly increased in the mucosal/submucosal layer at POD 3 or POD 7, whereas no significant difference was observed in the longitudinal muscle layers adherent with the myenteric plexus (LMMP). CONCLUSIONS: It is suggested that up-regulation of 5-HT3 and 5-HT4 receptors expression in the mucosal/submucosal layer is involved to restore the delayed transit after the parasympathetic denervation in rats.

Recovery of colonic transit following extrinsic nerve damage in rats.

INTRODUCTION: Injury to pelvic sympathetic and parasympathetic nerves from surgical and obstetrical trauma has long been cited as a cause for abnormal colorectal motility in humans. Using a rat model, acute transaction of these extrinsic nerves has been shown to effect colorectal motility. The aim of this study is to determine in a rat model how transection of these extrinsic nerves affects colonic transit over time. METHODS: Eighty-two Sprague-Dawley rats underwent placement of a tunneled catheter into the proximal colon. Bilateral hypogastric, pelvic nerves (HGN and PN) or both were transected in 66 rats. The remaining 16 rats received a sham operation. Colonic transit was evaluated at postoperative days (PODs) 1, 3, and 7 by injecting and calculating the geometric center (GC) of the distribution of (51)Cr after 3 h of propagation. RESULTS: At POD 1, transection of PNs significantly delayed colonic transit (GC = 4.9, p < 0.05), while transection of HGNs (GC = 8.5, p < 0.05) or transection of both nerves (GC = 7.8, p < 0.05) significantly accelerated colonic transit, when compared with sham operation (GC = 6.0). A significant trend toward recovery was noted in both the HGN and PN transection groups at POD 7. CONCLUSIONS: Damage to the extrinsic sympathetic and/or parasympathetic PNs affects colonic transit acutely. These changes in large bowel motor function normalize over time implicating a compensatory mechanism within the bowel itself.

Mechanism of acupuncture on neuromodulation in the gut--a review.

INTRODUCTION: Acupuncture has been used for treating various gastrointestinal (GI) diseases. However, the mechanism of acupuncture remains unclear. METHODS: The aim of this article is to review the published literature on the mechanism of acupuncture on neuromodulation in the gut. RESULTS: Acupuncture treatment involves the insertion of thin needles into the skin and underlying muscle and the subsequent stimulation of the needles manually or electrically. Thus, acupuncture stimulates the somatic afferent nerves of the skin and muscles. The somatic sensory information from the body is carried to the cortex area of the brain. Somatic sensory fibers also project to the various nuclei at the brain stem and hypothalamus. Via somato-autonomic reflex, acupuncture modulates various biomechanical responses, such as prokinetic, antiemetic, and anti-nociceptive effects. CONCLUSION: According to traditional Chinese medicine, "Acupuncture is believed to restore the balance of Yin and Yang." This can be translated into the Western medicine terminology that "Acupuncture modulates the imbalance between the parasympathetic and sympathetic activity." Acupuncture may be effective in patients with functional GI disorders because of its effects on GI motility and visceral pain.

Using a radiopaque marker with radiography for evaluating colonic transit by geometric center in conscious rats: A novel method.

This study developed a new method using radiopaque markers under X-ray to measure rat colonic transit by geometric center repeatedly and/or over a time series in the same individually. Additionally, the utility of this method was shown by elucidating the innervation of the autonomic nerve on colonic transit in detail with a pharmacological technique in conscious rats. An in-dwelling silastic cannula was inserted into the cecum and the proximal part was moved through the abdominal wall, where it was fixed to the posterior neck skin. Twenty markers were administered from the cannula to the proximal colon with saline on the fifth day after surgery. The markers were observed with soft X-ray before required repeated short anesthesia. Experimentation 1: Rats were measured colonic transit twice over 2 days with no administration. Experimentation 2: Rats were administered saline on the first day and pharmacology on the second day intraperitoneally before measurement. Experimentation 1: The markers administrated from the cannula and transited from proximal colon to distal colon over a time series. It showed no significant difference in complication rates between 2 days. Experimentation 2: The colonic transit was increasingly accelerated by neostigmine and phentolamine but not propranolol. Significant changes in 1.0 mg/kg atropine were noted although no differences were found between control and 0.05 mg/kg atropine and between each other's. We have presented the method using radiopaque markers under X-ray with short anesthesia for evaluating the colonic transit. The methods could show rat colonic transit changes in detail with a pharmacological technique.

Hypothalamic oxytocin mediates adaptation mechanism against chronic stress in rats.

Accumulation of continuous life stress (chronic stress) often causes gastric symptoms. Although central oxytocin has antistress effects, the role of central oxytocin in stress-induced gastric dysmotility remains unknown. Solid gastric emptying was measured in rats receiving acute restraint stress, 5 consecutive days of repeated restraint stress (chronic homotypic stress), and 7 consecutive days of varying types of stress (chronic heterotypic stress). Oxytocin and oxytocin receptor antagonist were administered intracerebroventricularly (icv). Expression of corticotropin-releasing factor (CRF) mRNA and oxytocin mRNA in the paraventricular nucleus (PVN) of the hypothalamus was evaluated by real-time RT-PCR. The changes of oxytocinergic neurons in the PVN were evaluated by immunohistochemistry. Acute stress delayed gastric emptying, and the delayed gastric emptying was completely restored after 5 consecutive days of chronic homotypic stress. In contrast, delayed gastric emptying persisted following chronic heterotypic stress. The restored gastric emptying following chronic homotypic stress was antagonized by icv injection of an oxytocin antagonist. Icv injection of oxytocin restored delayed gastric emptying induced by chronic heterotypic stress. CRF mRNA expression, which was significantly increased in response to acute stress and chronic heterotypic stress, returned to the basal levels following chronic homotypic stress. In contrast, oxytocin mRNA expression was significantly increased following chronic homotypic stress. The number of oxytocin-immunoreactive cells was increased following chronic homotypic stress at the magnocellular part of the PVN. Icv injection of oxytocin reduced CRF mRNA expression induced by acute stress and chronic heterotypic stress. It is suggested that the adaptation mechanism to chronic stress may involve the upregulation of oxytocin expression in the hypothalamus, which in turn attenuates CRF expression.

Central oxytocin is involved in restoring impaired gastric motility following chronic repeated stress in mice.

Accumulation of continuous life stress (chronic stress) often causes gastric symptoms. The development of gastric symptoms may depend on how humans adapt to the stressful events in their daily lives. Although acute stress delays gastric emptying and alters upper gastrointestinal motility in rodents, the effects of chronic stress on gastric motility and its adaptation mechanism remains unclear. Central oxytocin has been shown to have antistress effects. We studied whether central oxytocin is involved in mediating the adaptation mechanism following chronic repeated stress. Mice were loaded with acute and chronic stress (repeated stress for five consecutive days), and solid gastric emptying and postprandial gastric motility were compared between acute and chronic repeated stress. Expression of oxytocin and CRF mRNA in the hypothalamus was studied following acute and chronic repeated stress. Delayed gastric emptying during acute stress (43.1 +/- 7.8%; n = 6, P < 0.05) was completely restored to normal levels (72.1 +/- 2.4%; n = 6) following chronic repeated stress. Impaired gastric motility induced by acute stress was also restored following chronic repeated stress. Intracerebroventricular injection of oxytocin (0.1 and 0.5 microg) restored the impaired gastric emptying and motility induced by acute stress. The restored gastric emptying and motility following chronic repeated stress were antagonized by intracerebroventricular injection of oxytocin antagonists. Oxytocin mRNA expression in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus was significantly increased following chronic repeated stress. In contrast, increased CRF mRNA expression in the SON and PVN in response to acute stress was significantly reduced following chronic repeated stress. Our study suggests the novel finding that the upregulation of central oxytocin expression is involved in mediating the adaptation mechanism following chronic repeated stress in mice.

Physiological characteristics of gastric contractions and circadian gastric motility in the free-moving conscious house musk shrew (Suncus murinus).

Although many studies have demonstrated the physiological action of motilin on the migrating motor complex, the precise mechanisms remain obscure. To obtain new insights into the mechanisms, we focused on the house musk shrew (Suncus murinus, suncus used as a laboratory name) as a small model animal for in vivo motilin study, and we studied the physiological characteristics of suncus gastrointestinal motility. Strain gauge transducers were implanted on the serosa of the gastric body and duodenum, and we recorded gastrointestinal contractions in the free-moving conscious suncus and also examined the effects of intravenous infusion of various agents on gastrointestinal motility. During the fasted state, the suncus stomach and duodenum showed clear migrating phase III contractions (intervals of 80-150 min) as found in humans and dogs. Motilin (bolus injection, 100-300 ng/kg; continuous infusion, 10-100 ng·kg(-1)·min(-1)) and erythromycin (80 µg·kg(-1)·min(-1)) induced gastric phase III contractions, and motilin injection also increased the gastric motility index in a dose-dependent manner (P < 0.05, vs. saline). Pretreatment with atropine completely abolished the motilin-induced gastric phase III contractions. On the other hand, in the free-feeding condition, the suncus showed a relatively long fasting period in the light phase followed by spontaneous gastric phase III contractions. The results suggest that the suncus has almost the same gastrointestinal motility and motilin response as those found in humans and dogs, and we propose the suncus as a new small model animal for studying gastrointestinal motility and motilin in vivo.

Sensory Stimulation of Oxytocin Release Is Associated With Stress Management and Maternal Care.

It has been shown that various types of stress initiate different physiological and neuroendocrine disorders. Oxytocin (OT) is mainly produced in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus. Hypothalamic OT has antistress effects and attenuates the hypothalamic-pituitary-adrenal (HPA) axis. One mechanism behind the antistress effects of OT is mediated through the inhibition from GABAA receptors on corticotropin-releasing factor (CRF) expression at the PVN. Various manual therapies such as acupuncture, transcutaneous electrical nerve stimulation (TENS), and massage initiate the stimulation of somatosensory neurons of the body. It is well-known that TENS simulates OT expression, while it inhibits CRF expression at the PVN following chronic stress loading in rodents. Upregulation of OT expression at the hypothalamus is activated by the somatosensory stimulation, which is mediated via the spinothalamic pathway (the connection between the spinal cord and hypothalamus). Thus, somatosensory stimulation is beneficial in treating stress-associated symptoms. Hypothalamic OT is associated with the social behaviors, including maternal care and affiliation. Childhood neglect and/or child abuse are severely responsible for deleterious long-term effects on the cognitive/social activity and behavioral development. At parturition, a profound amount of OT is released into the systemic circulation in response to vaginal and cervical stimulation caused by the body of fetus, which induces the onset of maternal behavior. Peridural anesthesia effectively impairs the sensitivity to vaginal and cervical stimulation at parturition. OT levels in cerebrospinal fluid is significantly reduced following peridural anesthesia. The vaginal delivery mothers had significantly more OT pulses than the caesarian section (CS) mothers. Due to low levels of endogenous OT, maternal behavior could be interrupted by epidural anesthesia and CS at parturition because of the reduction of the usual sensory input from the genitalia.

Extrinsic surgical denervation ameliorates TNBS-induced colitis in rats.

BACKGROUND/AIMS: Neurogenic inflammation refers to an inflammatory reflex arc by sensory neurons which transmit nocious stimulus centrally and results in both pain perception and intense local inflammatory reaction. Specific neurons, receptors, and their respective neurotransmitters have been studied in numerous organ systems including the gastrointestinal tract. Neurogenic inflammation has been suggested to play a key role in the pathogenesis of inflammatory bowel disease. In this study, we studied the effect of surgical denervation of specific somatosensory neurons in a well-established animal model of colitis. METHODOLOGY: Adult male rats were underwent surgical denervation around the inferior mesenteric artery or sham operation. After ten days trinitrobenzene sulfonic acid (TNBS) or vehicle was administered by enema. Inflammation was assessed by, histological evaluation, macroscopic damage score, myeloperoxidase (MPO) activity, and substance P receptor immunoreactivity (SPRIR). RESULTS: Compared with sham operation with TNBS administration, surgical denervation with TNBS administration suppressed the score in all of the inflammatory indices and had almost no signs of inflammation in histological evaluation. CONCLUSIONS: Surgical denervation has a protective effect on TNBS-induced colitis in rats. Thus, sensory neurons play a key role in the pathogenesis of inflammation in this well-established model of acute colitis.

Electroacupuncture improves imbalance of autonomic function under restraint stress in conscious rats.

Acupuncture may modulate the imbalance of the autonomic nervous system. It is well known that restraint stress delays gastric emptying via inhibiting parasympathetic activity and/or stimulating sympathetic activity in rats. We have previously shown that electroacupuncture (EA) improves delayed gastric emptying induced by restraint stress in rats. To investigate whether the beneficial effect of EA on delayed gastric emptying is associated with its modulatory effects on autonomic nervous activity, we utilized spectral analysis of heart rate variability (HRV). In rats, the power in the low frequency (LF; 0.04-1.0 Hz) and high frequency (HF; 1.0-3 Hz) band of HRV represent sympathetic and parasympathetic activities, respectively. Electrocardiography (ECG)-electrodes were implanted on the subcutaneous tissues of the back. One week after the surgery, ECG was recorded before, during and after the restraint stress loading in a conscious state. EA (10 Hz) was applied at bilateral acupuncture points [ST-36 (lower leg) or BL-21 (back)] during restraint stress loading. In response to restraint stress, heart rate and LF component were increased, suggesting the increased activity of sympathetic tone. EA at ST-36 significantly reduced the elevated heart rate and LF, compared to that of control group. EA at ST-36 also significantly increased HF component after finishing the stress loading. In contrast, EA at BL-21 had no significant effect on the heart rate, LF and HF. It is suggested that EA at ST-36 stimulates parasympathetic activity and inhibits sympathetic activity under the restraint stress in rats.

Ghrelin accelerates gastric emptying via early manifestation of antro-pyloric coordination in conscious rats.

Ghrelin is known to enhance gastric motility and accelerate gastric emptying of liquid and solid food in rats. As solid gastric emptying is regulated by the coordinated motor pattern between the antrum and pylorus (antro-pyloric coordination), we studied the correlation between solid gastric emptying and antro-pyloric coordination in response to ghrelin. Rats were given 1.5 g of solid food after a 24-h fasting. Immediately after the ingestion, ghrelin (0.4-8.0 microg/kg) or saline was administered by intraperitoneal (i.p.) injection. Ninety minutes after the feeding, rats were euthanized and gastric content was removed to calculate gastric emptying. To evaluate the antro-pyloric coordination, strain gauge transducers were sutured on the antrum and pylorus. The incidence of postprandial antro-pyloric coordination was compared between ghrelin-and saline-injected rats. In saline-injected rats, gastric emptying was 58.3+/-3.7% (n=6). Ghrelin (4.0-8.0 microg/kg), accelerated gastric emptying. Maximum effect was obtained by ghrelin (4.0 microg/kg), which significantly accelerated gastric emptying to 77.4+/-3.7% (n=6, p<0.05). The number of antro-pyloric coordination 20-40 min after feeding was significantly increased in ghrelin-injected rats, compared to that of saline-injected rats (n=4, p<0.05). It is suggested that enhanced antro-pyloric coordination play an important role in accelerated solid gastric emptying induced by ghrelin.

Effects of ghrelin on interdigestive contractions of the rat gastrointestinal tract.

Ghrelin causes interdigestive contractions of the stomach in rats. However, it remains unknown whether ghrelin causes interdigestive contractions in the small intestine. Four strain gauge transducers were implanted on the antrum, duodenum, proximal and distal jejunum. After an overnight fast, gastrointestinal (GI) contractions were recorded in freely moving conscious rats. Spontaneous phase III-like contractions were observed at every 13-16 min in rat GI tract. The fasted motor patterns were replaced by the fed motor pattern immediately after food intake. Two minutes after finishing the spontaneous phase III-like contractions in the antrum, acyl ghrelin (0.8, 2.4 and 8.0 microg/kg per min) was continuously infused for 30 min. Three-five minutes after the starting ghrelin infusion, augmented phase III-like contractions were observed at the antrum, duodenum, and jejunum. Ghrelin infusion (0.8, 2.4 and 8.0 microg/kg per min) significantly increased motility index of phase III-like contractions at the antrum and jejunum in a dose dependent manner, compared to that of saline injection. Thus, it is likely that exogenously administered ghrelin causes phase III-like contraction at the antrum, which migrates to the duodenum and jejunum. The possible role of 5-HT, in addition to ghrelin, in mediating intestinal migrating motor complex (MMC), is discussed.

Peripheral plasma corticotropin-releasing factor concentration does not correlate with augmented colonic motility in response to restraint stress in rats.

1. Corticotropin-releasing factor (CRF) alters colonic motor function in response to restraint stress. It remains unclear whether peripheral CRF released by restraint stress correlates with stress-mediated colonic motility. 2. One strain gauge transducer was sutured on the serosal surface of the mid colon and a silastic cannula was inserted into the jugular vein. Seven days after surgery, the wires from the transducers were connected to the recording system and colonic motility was recorded. Rats were subjected to restraint stress for 90 min and blood samples were obtained every 30 min. 3. Immediately after the start of stress loading, phasic contractions were observed that lasted during restraint stress loading. Intracisternal injection of CRF elicited rapid augmentation of colonic motility, similar to that of restraint stress. 4. The plasma CRF concentration (4 pg/mL) remained unaltered within the first 30 min after stress loading, but increased gradually to 23 pg/mL at 90 min after the beginning of restraint stress. There was no positive correlation observed between plasma CRF concentrations and restraint stress-stimulated colonic motility. 5. These findings indicate that central CRF has a predominant role in stress-induced augmentation of colonic motility. It remains unclear whether a delayed response of plasma CRF concentrations in response to restraint stress is involved in mediating colonic motility.

Effects of electroacupuncture on gastric motility and heart rate variability in conscious rats.

To clarify the mechanism of site-specific effects of acupuncture on gastric motor function, we studied the simultaneous recording of gastric motility and electrocardiogram (ECG) for heart rate variability (HRV) analysis in conscious rats. Gastric motility and ECG were recorded before, during and after electroacupuncture (EA) at ST-36 (hind limb) or ST-25 (abdomen). EA at ST-36 significantly increased gastric motility and decreased the ratio of low frequency (LF)/high frequency (HF) of the HRV analysis. In contrast, EA at ST-25 significantly inhibited gastric motility and increased LF/HF ratio. There was a significant correlation observed between the changes of gastric motility and LF/HF ratio in response to EA. It is suggested that the stimulatory effect of EA at ST-36 on gastric motility is associated with its stimulatory effect on vagal activity. The inhibitory effect of EA at ST-25 on gastric motility is associated with its stimulatory effect on the sympathetic nerve activity.

Functional evaluation of the grafted wall with porcine-derived small intestinal submucosa (SIS) to a stomach defect in rats.

BACKGROUND: Small intestinal submucosa (SIS) represents a novel bio-scaffolding material that may be used to repair hollow-organ defects. However, it is unclear whether neurophysiologic responses return to SIS-grafted areas in the gut. We evaluated the functional recovery of a stomach defect grafted with the porcine-derived SIS. METHODS: Twelve rats had a full-thickness defect created in the stomach. SIS was secured to the gastric wall. After 6 months, muscle strips were harvested from within the grafted area to perform both a histologic and a functional study. Additional full-thickness muscle strips were harvested from the posterior in the same stomach as controls. A dose response curve was obtained with carbachol (CCH) or sodium nitroprusside (SNP). Activation of intrinsic nerves was achieved by electrical field stimulation (EFS). RESULTS: The response to CCH and amplitude in EFS showed tonic contraction in both controls and SIS strips in a concentration-dependent and frequency-dependent manner. The magnitude after each stimulation was significantly lower in SIS strips compared with controls (P < .01). However, the contraction ratio of EFS to ED(50) of CCH was not significantly different between the groups. Additionally, SNP produced relaxation in both strips in a concentration-dependent manner. Histologic findings revealed that an insufficient amount of smooth-muscle cells existed in the muscularis propria, whereas compensated growth was observed in the submucosa with nerve regeneration. CONCLUSIONS: This study demonstrates that SIS provides a template for nerve migration to the graft in the rodent stomach. Innervations showed a similar distribution to that observed in the controls. The clinical implications of such findings warrant additional investigation.

Central effects of morphine on GI motility in conscious dogs.

It has been suggested that morphine has dual effects; emetic effects and anti-emetic effects. The chemoreceptor trigger zone, which is outside the BBB, mediates the emetic effect. In contrast, the vomiting center mediates the anti-emetic effect of opioids. Thus, naloxone methiodide, which does not cross the BBB, antagonizes emetic effects of opioids. We studied whether naloxone methiodide alters abnormal motility pattern induced by morphine in gastrointestinal (GI) tract. Strain gauge force transducers were sutured on the serosal surface of upper GI tract to record the circular muscle contractions in eight dogs. The ventricular access system was implanted to inject morphine intracerebroventricularly (icv). Effects of icv-injection of morphine (0.3-3.0 mug/kg, bolus) on GI motility were studied during intravenous infusion of naloxone hydrochloride or naloxone methiodide. Icv-injection of morphine (3.0 mug/kg) induced retching and vomiting in all dogs tested. Phasic contractions of the jejunum were observed after icv-injection of morphine. These contractions in the jejunum migrated orally to the antrum (retrograde peristaltic contractions; RPCs). Both naloxone hydrochloride and naloxone methiodide treatment virtually abolished the emetic effects of morphine. Naloxone hydrochloride completely abolished morphine-induced RPCs in all dogs, whereas naloxone methiodide converted morphine-induced RPCs to anterograde peristaltic contractions (APCs) in 6 of 8 dogs. Our current study suggests that central opioids may induce APCs and prevent emesis in conscious dogs. Naloxone methiodide may be useful to prevent the undesired side effects of morphine.

Fecal pellet output does not always correlate with colonic transit in response to restraint stress and corticotropin-releasing factor in rats.

BACKGROUND: Fecal pellet output has been assessed as a colonic motor activity because of its simplicity. However, it remains unclear whether an acceleration of colonic transit correlates well with an increase in fecal pellet output. We examined the causal relationship between colonic transit and fecal pellet output stimulated by the central application of corticotropin-releasing factor (CRF) and restraint stress. METHODS: Immediately after intracisternal injection of CRF, (51)Cr was injected via a catheter positioned in the proximal colon. Ninety minutes after (51)Cr injection, the total number of excreted feces was counted, and then the rats were killed. The radioactivity of each colonic segment was evaluated, and the geometric center (GC) of the distribution of (51)Cr was calculated. For the restraint stress study, after administration of (51)Cr into the proximal colon, rats were submitted to wrapping restraint stress for 90 min. Then they were killed, and GC was calculated. RESULTS: Both restraint stress and CRF significantly accelerated colonic transit. There was a positive correlation observed between fecal pellet output and GC of colonic transit in response to restraint stress, but not CRF, when the number of excreted feces was more than three. In contrast, there was no significant correlation observed between the two in stress and CRF when the number of excreted feces was less than two. CONCLUSIONS: The acceleration of colonic transit in response to restraint stress and central administration of CRF does not always correlate with an increase in fecal pellet output.