Transient receptor potential vanilloid-1 (TRPV1), a nonselective cation channel, is activated by capsaicin, a pungent ingredient of hot pepper. Previous studies have suggested a link between obesity and capsaicin-associated pathways, and activation of TRPV1 may provide an alternative approach for obesity treatment. However, data on the TRPV1 distribution in human gastric mucosa are limited, and the degree of TRPV1 distribution in the gastric and duodenal mucosal cells of obese people in comparison with normal-weight individuals is unknown.

To clarify gastric and duodenal mucosal expression of TRPV1 in humans and compare TRPV1 expression in obese and healthy individuals.

Forty-six patients with a body mass index (BMI) of > 40 kg/m2 and 20 patients with a BMI between 18-25 kg/m2 were included. Simultaneous biopsies from the fundus, antrum, and duodenum tissues were obtained from subjects between the ages of 18 and 65 who underwent esophagogastroduodenoscopy. Age, sex, history of alcohol and cigarette consumption, and past medical history regarding chronic diseases and medications were accessed from patient charts and were analyzed accordingly. Evaluation with anti-TRPV1 antibody was performed separately according to cell types in the fundus, antrum, and duodenum tissues using an immunoreactivity score. Data were analyzed using SPSS 17.0.

TRPV1 expression was higher in the stomach than in the duodenum and was predominantly found in parietal and chief cells of the fundus and mucous and foveolar cells of the antrum. Unlike foveolar cells in the antrum, TRPV1 was relatively low in foveolar cells in the fundus (4.92 ± 0.49 vs 0.48 ± 0.16, P < 0.01, Mann-Whitney U test). Additionally, the mucous cells in the duodenum also had low levels of TRPV1 compared to mucous cells in the antrum (1.33 ± 0.31 vs 2.95 ± 0.46, P < 0.01, Mann-Whitney U test). TRPV1 expression levels of different cell types in the fundus, antrum, and duodenum tissues of the morbidly obese group were similar to those of the control group. Staining with TRPV1 in fundus chief cells and antrum and duodenum mucous cells was higher in patients aged ≥ 45 years than in patients < 45 years (3.03 ± 0.42, 4.37 ± 0.76, 2.28 ± 0.55 vs 1.9 ± 0.46, 1.58 ± 0.44, 0.37 ± 0.18, P = 0.03, P < 0.01, P < 0.01, respectively, Mann-Whitney U test). The mean staining levels of TRPV1 in duodenal mucous cells in patients with diabetes and hypertension were higher than those in patients without diabetes and hypertension (diabetes: 2.11 ± 0.67 vs 1.02 ± 0.34, P = 0.04; hypertension: 2.42 ± 0.75 vs 1.02 ± 0.33, P < 0.01 Mann-Whitney U test).

The expression of TRPV1 is unchanged in the gastroduodenal mucosa of morbidly obese patients demonstrating that drugs targeting TRPV1 may be effective in these patients.

Capsaicin, which is the major pungent principle in chili peppers, is able to induce satiety and reduce caloric intake. The exact mechanism behind this satiating effect is still unknown. We hypothesized that capsaicin induces satiety through the release of gastrointestinal peptides, such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), from enteroendocrine cells in the small intestine.

We investigate the effects of an intraduodenal capsaicin infusion (1.5 mg pure capsaicin) in healthy volunteers on hunger, satiety, and gastrointestinal symptoms and the release of GLP-1 and PYY.

Thirteen participants (7 women) [mean ± SEM age: 21.5 ± 0.6 y; body mass index (in kg/m(2)): 22.8 ± 0.6] participated in this single-blind, randomized, placebo-controlled crossover study with 2 different treatments. During test days, an intraduodenal infusion of either capsaicin or a placebo (physiologic saline) was performed with the use of a nasoduodenal catheter over a period of 30 min. Visual analog scale scores were used to measure hunger, satiety, and gastrointestinal symptoms. Blood samples were drawn at regular intervals for GLP-1 and PYY. Gallbladder volumes were measured with the use of real-time ultrasonography.

The intraduodenal capsaicin infusion significantly increased satiety (P-treatment effect < 0.05) but also resulted in an increase in the gastrointestinal symptoms pain (P-treatment × time interaction < 0.0005), burning sensation (P-treatment × time interaction < 0.0001), nausea (P-treatment × time interaction < 0.05), and bloating (P-treatment × time interaction < 0.001) compared with the effects of the placebo infusion. Satiety scores had a positive correlation with all gastrointestinal symptoms. No differences in GLP-1 and PYY concentrations and gallbladder volumes were observed after the capsaicin infusion compared with after the placebo infusion.

An intraduodenal infusion of capsaicin significantly increases satiety but does not affect plasma concentrations of GLP-1 and PYY. Rather, the effect on satiety seems related to gastrointestinal stress as shown by the associations with pain, burning sensation, nausea, and bloating scores. This trial was registered at clinicaltrials.gov as NCT01667523.

We, herein, examined the role of the intraluminal contents and continuity of colonic intrinsic neurons in intracolonic capsaicin-induced enhancement of colonic motility and defecation.

Five beagle dogs were equipped with three strain gauge force transducers throughout the colon. The colonic contractile activity in response to intracolonic capsaicin was studied in intact dogs, dogs after colonic cleansing and dogs with transection/re-anastomosis (T/R) between the proximal and middle colon. The effects of intravenous yohimbine, a α2 adrenergic antagonist, on the colonic motility and defecation were also studied in the same models.

In intact dogs, capsaicin (10 mg) and yohimbine (2 mg/kg) immediately induced contractions throughout the colon, with defecation occurring in all experiments. In dogs after colonic cleansing and T/R, the capsaicin (10 mg)-induced enhancement of colonic motility was decreased in the middle and distal colon, and capsaicin-induced defecation was observed in 0-20 % of experiments (p < 0.05 compared to intact dogs). The effect of yohimbine (2 mg/kg) in inducing colonic contractions was unaltered after colonic cleansing and T/R; in contrast, yohimbine-induced defecation was not observed after colonic cleansing, but was unchanged after T/R.

The continuity of the colonic intrinsic nerves as well as the intraluminal contents appear to play an important role in the colonic motor response to intracolonic capsaicin.

The aim of this study was to investigate the effects of intracolonic capsaicin on colonic motility and defecation.

The effects of capsaicin (1, 2, 5, and 10 mg) administrated into the proximal colon on ileocolonic motility and defecation were studied in neurally intact dogs with or without various antagonists (atropine, hexamethonium, ondansetron, propranolol, and FK224), dogs with extrinsic denervation of an ileocolonic segment, and dogs with enterically isolated ileocolonic loops equipped with strain gauge force transducers.

Capsaicin at 5 and 10 mg evoked giant migrating contractions in a dose-independent manner, and it induced defecations with more than 90% probability in neurally intact dogs. These effects of capsaicin were abolished by atropine and hexamethonium. Ondansetron inhibited the capsaicin-induced increase in colonic motility but did not affect the induction of defecation. The other antagonists had no effect. In dogs with extrinsic denervation, capsaicin did not evoke giant migrating contractions in the colon but still induced defecation in 30-40% of experiments. In dogs with ileocolonic loops, capsaicin did not stimulate colonic motility nor induce defecation.

These results indicate that intracolonic capsaicin causes giant migrating contractions and defecation. Intact extrinsic innervation, continuity of the colon, and intraluminal contents were considered necessary for this effect.

The administration of stimuli to the ileum inhibits upper gastrointestinal motility. The aim of this study was to determine whether a total colectomy can alter this motor inhibitory effect.

Beagle dogs were each equipped with four strain gauge force transducers on the upper gastrointestinal tract. The infusion of nutrients (saline as placebo control, oleate, butyrate, and glucose) began 90 min after feeding and continued for 30 min via a silicone catheter placed in the ileal lumen. Capsaicin (10 mg) was injected into the ileum as a bolus. All of the dogs underwent a relaparotomy and a total colectomy, and the same experiments were performed on all dogs.

Before performing a colectomy, the oleate, the glucose, and the capsaicin were each found to inhibit the postprandial upper gastrointestinal motility in comparison to the placebo control (P < 0.05). The butyrate had no inhibitory effect. After a total colectomy, the inhibition of upper gastrointestinal motility was observed after the intraileal infusion of the oleate and the capsaicin (P < 0.05). The motor inhibitory response to the intraileal glucose was delayed after a total colectomy, and a reduction of the motility index was not observed in the gastric antrum and the duodenum because of this delay. However, a significant reduction in the motility index was observed in the jejunum.

The intraileal stimuli-induced motor inhibition decreased after a total colectomy after the administration of glucose, but not after the administration of either oleate or capsaicin.

The aim of this study was to evaluate the effect of growth hormone releasing peptide (GHRP)-2, a synthetic ligand for the growth hormone secretagogue receptor, on upper gastrointestinal motility and food intake.

Five neurally intact dogs and five dogs with vagotomy and pyloroplasty were equipped with strain gauge force transducers on the stomach, duodenum and jejunum. GHRP-2 (0.5-10 microg/kg) was administered intravenously in neurally intact dogs in the interdigestive state and after feeding. To study the mechanism of GHRP-2-induced inhibition on postprandial contractions, various antagonists were administered intravenously prior to GHRP-2. The effect of GHRP-2 on postprandial contractions was also studied in dogs with vagotomy. GHRP-2 was also administered immediately before feeding in each group, and its effect on food intake was assessed.

GHRP-2 did not evoke gastrointestinal contractions in the interdigestive state. GHRP-2 induced contractile inhibition continuing for 2-3 min in neurally intact dogs and dogs with vagotomy. This inhibitory effect was reversed by the alpha- and alpha(2)-blockers. GHRP-2 increased food intake in neurally intact dogs, but not in dogs with vagotomy.

These results indicate that in the upper gut GHRP-2 inhibits postprandial contractions via alpha(2)-receptors on the enteric nervous system, whereas an intact vagal nerve is necessary for a GHRP-2-induced increase in food intake.

Repeated ingestion of capsaicin over a prolonged period reduces symptoms in functional dyspepsia, but initially induces upper abdominal symptoms. Sensitizing chemonociception might be the cause for this initial effect of capsaicin. The aim was to evaluate the effect of prolonged capsaicin ingestion on duodenal chemo- and mechanonociception. Healthy subjects ingested capsules containing either 0.25 mg capsaicin tid (n = 8) or placebo (n = 8) for 28 days. Before (day 0) and after (day 29) capsule ingestion the duodenum was distended with a balloon and perfused with a capsaicin solution. Mechanically and chemically induced sensation was evaluated by a graded questionnaire. Aggregate perception scores were calculated. Perception scores during balloon distensions with 12 and 18 mmHg were significantly lower after 4 weeks capsaicin when compared to baseline (P < 0.05). Balloon volumes to induce first sensation (63 +/- 14 mL (day 0) vs 92 +/- 22 mL (day 29); P < 0.05) and discomfort (101 +/- 12 mL vs 137 +/- 22 mL; P = 0.05) where significantly higher after 4 weeks capsaicin application; balloon pressures to induce sensations were not significantly different. Intraluminal capsaicin application induced first sensation after 3.4 +/- 1.5 min (day 0) and 7.5 +/- 4.6 min (day 29) (P < 0.05) and discomfort after 15.9 +/- 9.8 min and 22.4 +/- 7.3 min (P < 0.05). The quality of perception was not altered by repeated capsaicin ingestion. In the placebo group, mechano- and chemonociception remained unaltered at day 29. Four weeks ingestion of capsaicin desensitized both chemonociceptive and mechanonociceptive pathways in healthy volunteers. Symptom reduction after prolonged treatment with capsaicin in dyspeptic patients might be attributed to a dual desensitizing effect of capsaicin on chemonociceptors and mechanonociceptors.

Capsaicin is known to have regulatory effects on gastrointestinal functions via the vanilloid receptor (VR1). We reported previously that endocrine-like cells in the human antrum express VR1.

To identify VR1-expressing endocrine-like cells in human antral glands and to examine whether stimulation with capsaicin causes release of gastrin, somatostatin, and serotonin. Further, to investigate the effects of a chilli-rich diet.

Gastroscopic biopsies were received from 11 volunteers. Seven of the 11 subjects agreed to donor gastric biopsies a second time after a 3-week chilli-rich diet containing 1.4-4.2 mg capsaicin/day. VR1-immunoreactive cells were identified by double-staining immunohistochemistry against gastrin, somatostatin, and serotonin. For the stimulation studies, we used an in vitro method where antral glands in suspension were stimulated with 0.01 mM capsaicin and physiological buffer was added to the control vials. The concentrations of secreted hormones were detected and calculated with radioimmunoassay (RIA). Results The light microscopic examination revealed that VR1 was localized in gastrin cells. The secretory studies showed an increase in release of gastrin and somatostatin compared to the control vials (P = 0.003; P = 0.013). Capsaicin-stimulation caused a consistent raise of the gastrin concentrations in the gland preparations from all subjects. A chilli-rich diet had an inhibitory effect on gastrin release upon stimulation compared to the results that were obtained before the start of the diet.

This study shows that capsaicin stimulates gastrin secretion from isolated human antral glands, and that a chilli-rich diet decreases this secretion.

The aim was to investigate the effects of alpha(2)-adrenoceptor antagonist yohimbine on colonic motility and defecation. The effects of yohimbine (0.5, 1.0, and 3.0 mg/kg) on colonic motility and defecation were studied in neurally intact dogs (N=6), dogs with extrinsic denervation of the ileocolon (N=4), and dogs with enterically isolated ileocolnic loops (N=5) equipped with strain gauge force transducers on the ileocolon. The effects of yohimbine on colonic motility and defecation were also studied in the presence of various antagonists (atropine, hexamethonium, ondansetron, FK224, and naloxone). Yohimbine evoked giant migrating contractions and defecation in a dose-independent manner in neurally intact dogs. These stimulatory effects of yohimbine were abolished by atropine and hexamethonium. In dogs with extrinsic denervation, yohimbine induced giant migrating contractions in the colon but did not stimulate defecation. In dogs with ileocolonic loops, yohimbine induced colonic motor complexes but not giant migrating contractions in the enterically isolated colon. These results indicate that alpha(2)-adrenoceptors in the peripheral nervous system regulate giant migrating contractions by controlling the release of acetylcholine, while those in the central nervous system must be important in the regulation of defecation.

Slow waves play an important role in controlling the frequency and propagation of gastrointestinal contractions. However, mechanisms involved in the modulation of slow wave activity in vivo are still unclear. In this study, the roles of different neurotransmitters in the regulation of gastrointestinal slow waves were investigated in conscious dogs.

Female dogs implanted with electrodes in the stomach and the small bowel were used in a seven-session study. Gastrointestinal myoelectrical activity was recorded at baseline and after i.v. saline, atropine, atropine methyl nitrate, guanethidine, Nomega-nitro-L-arginine (L-NNA), ondansetron or naloxone.

Both atropine and atropine methyl nitrate induced tachygastria, bradygastria and arrhythmia. No difference was noted in the effects between atropine and atropine methyl nitrate. L-NNA increased the dominant frequency of small-intestinal slow waves but had no effect on gastric slow waves. Guanethidine, ondansetron and naloxone did not affect the dominant frequency, power or percentage of normal gastrointestinal slow waves.

Acetylcholine acting at muscarinic receptors seems to play an important role in the regulation of gastric slow waves. Nitric oxide may play a role in modulating intestinal slow waves but not gastric slow waves. Sympathetic pathways, 5-HT(3) receptors and opioid receptors (especially micro-opioid receptors) do not play a role in the regulation of gastric or intestinal slow waves under normal physiological conditions.

Ingestion of capsaicin reduces symptoms in functional dyspepsia but induces upper abdominal symptoms initially.

To evaluate the effects of one week of oral dosing with capsaicin on mechanonociception and chemonociception.

Healthy subjects ingested capsules containing 0.5 mg capsaicin t.d.s (n = 8) or placebo (n = 5) for 7 days. Before (day 0) and after (day 8) capsule ingestion the jejunum was distended with a balloon and perfused with a capsaicin solution. A graded questionnaire evaluated distension- and capsaicin-induced sensation, aggregate perception scores were calculated.

Infusion of capsaicin induced sensations similar to distension. In subjects receiving capsaicin capsules, mean +/- S.E.M. perception scores at 24 mL distension volumes were 4.7 +/- 1.2 (day 0) and 3.2 +/- 1.3 (day 8, N.S.). Distension with 40 mL induced perception scores of 10.3 +/- 1.0 vs. 8.2 +/- 1.0 (P < 0.05). During capsaicin perfusion, first sensation was reported after 13.2 +/- 1.9 min (day 0) and 8.1 +/- 0.8 min (day 8, N.S.), discomfort thresholds after 44.1 +/- 6.0 and 31.2 +/- 5.7 min (P < 0.05). In the placebo group, mechano- and chemonociception remained unaltered on days 0 and 8.

One week of ingestion of capsaicin sensitized chemonociceptors, while sensitivity of mechanonociceptors for distension decreased. Painful sensations during the first week of treatment with capsaicin can be attributed to a sensitizing effect of capsaicin on vanilloid receptors.

The effects and mechanisms of intestinal electrical stimulation (IES) with long pulses on intestinal motility were investigated in conscious dogs. Eighteen dogs were equipped with serosal electrodes and an intestinal cannula in the small bowel. The first experiment was designed to study the effect of one-channel IES on intestinal motility and the extent of this effect. The second experiment was conducted to study the effect of IES on intestinal motility and the involvement of neural pathway. The IES with long pulses significantly inhibited intestinal motility. Intestinal motility of the entire measured segment (40-220 cm distal to the stimulation electrodes) was inhibited by 60-74% with the single-channel IES with long pulses. Hexamethonium, guanethidine, phentolamine, propranolol partially, but not N(omega)-nitro-L-arginine (L-NNA), ondansetron and naloxone prevented the inhibitory effect of IES on intestinal motility. We conclude that single-channel IES inhibits intestinal motility within a distance of at least 2 m. This inhibitory effect induced by IES with long pulses is mediated via sympathetic but not nitrergic, serotoninergic 5-HT(3) and opiate pathway.

In the past year, many studies were published in which new and relevant information on small intestinal motility in humans and laboratory animals was obtained.

Although the reported findings are heterogeneous, some themes appear to be particularly interesting and novel. Among these is the association between disordered small intestinal motility and bacterial overgrowth of the small intestine. Studies in patients with portal hypertension, in patients with chronic renal failure, and in a rat model of experimental acute pancreatitis all point in the same direction. Another topic of particular interest is the relation between duodenal motility and glucose absorption; propagated duodenal pressure wave sequences are positively related to glucose absorption. Finally, many studies addressed the mechanisms involved in the regulation of interdigestive and postprandial small intestinal motility. These confirmed the key role of cholecystokinin and provided new information on the role of orexin A and leptin.

The new information on intestinal motility gathered in the past year provides a greater insight in the pathophysiology of a number of diseases and will stimulate further studies in laboratory animals and in human subjects.