Gastrointestinal Motility Issues in Cancer Patients.

PURPOSE OF REVIEW: This paper seeks to highlight GI motility disorders that are frequently present in patients with a malignancy. GI dysmotility can occur due to the cancer itself or as a consequence of medical and surgical treatments. Often, symptoms are nonspecific and the diagnosis requires a high index of suspicion. The goal of the paper is to review the common motility problems seen in patients with cancer, their clinical manifestations, and options for management. RECENT FINDINGS: Studies show that newer endoscopy techniques such as endoscopic mucosal dissection can cause esophageal dysmotility. Opioid-induced constipation is frequently encountered in patients with cancer. Motility disorders in cancer patient can lead to clinical morbidity, poor quality of life, and malnutrition. Newer diagnostic tests and medical and surgical treatments may be helpful in improving the diagnosis and management of these disorders.

High-Dose Radiation-Induced Changes in Murine Small Intestinal Motility: Are the Changes in the Interstitial Cells of Cajal or in the Enteric Nervous System?

Murine small intestinal motility consists of phasic contraction from interstitial cells of Cajal (ICC) and migrating motor complexes (MMCs) from the enteric nervous system. The number of ICC is reduced in various gastrointestinal disorders, and this effect can be reversed once the disorder is resolved through cellular and tissue remodelling. Exposure to high-dose radiation can induce inflammation and alter intestinal motility. In this study, we investigated the changes in the small intestinal motility of 8- to 10-week-old male C3H/HeN mice after high-dose (13 Gy) irradiation. The aim of this study was to determine whether those changes are caused by changes in the ICC or enteric nervous system. After irradiation, the small intestine was dissected and stored in oxygenated Krebs-Ringer bicarbonate solution. The tension of contractions and intracellular membrane potentials were recorded at day 0, 1, 3 and 5 after irradiation and compared with those of sham-irradiated mice. Histological evaluation was performed by immunohistochemistry and apoptosis was evaluated. Quantitative real-time polymerase chain reaction (qPCR) for c-kit mRNA was also performed. Phasic contractions were not changed at day 0, 1, 3 and 5 after irradiation and did not significantly differ from those in the control mice. Slow waves were also sustained after irradiation. However, the frequency of migrating motor complexes (MMCs) was significantly higher at day 0 and 1 after exposure and the amplitude and area under the curve were significantly lower at day 3 after exposure compared with control mice. MMCs were recovered at day 5 with no difference from those of the control mice. ICC were detected after irradiation by immunohistochemistry for c-kit, and c-kit mRNA levels did not differ between sham-irradiated and irradiated mice. Histological evaluation showed that the most severe inflammation was detected at day 3 after irradiation, and apoptosis was detected only in the mucosa. Acetylcholine increased the contractility after irradiation, and tetrodotoxin decreased the number of MMCs in sham-irradiated and irradiated mice. N(w)-oxide-l-arginine (L-NA) increased the number of MMCs. MMCs were recovered after L-NA treatment at day 3 after irradiation. Sodium nitroprusside decreased the MMCs in sham-irradiated and irradiated mice. Exposure to high-dose radiation did not alter phasic contractions and slow waves in the small intestine of mice, which suggests that ICC and their functions may be sustained after high-dose irradiation. Mucosal inflammation was severe after irradiation and there were some changes in MMCs related to the enteric nervous system.

Gut fibrosis with altered colonic contractility in a mouse model of scleroderma.

OBJECTIVE: Gastrointestinal involvement occurs in up to 90% of patients with SSc. Animal models of SSc mimic some of the pathophysiological disease processes of SSc. The transgenic (TG) mouse strain TßRIIΔk-fib is characterized by ligand-dependent up-regulation of TGF-ß signalling and has been shown to develop skin fibrosis, lung fibrosis and diminished aortic ring contractility and adventitial fibrosis. We investigated if similar changes are observed in the gut tissue in this mouse model. METHODS: Colonic tissue was examined using histology and immunohistochemistry analyses. Tissue architecture was examined by haematoxylin and eosin (H&E), picrosirius red and immunohistochemical markers for α-smooth muscle actin (α-SMA), phospho-Smad 2/3 (pSmad2/3), Ki-67, protein gene product 9.5 and S-100. Fibrosis was quantified using the NIS Elements BR 2.30 system and by Sircol assay. Colonic strip contractile responses to potassium chloride (KCl) and carbachol were assessed in isolated organ baths. Confirmatory gut fibroblast and intestinal tissue biochemical assays, including cellular signalling mechanisms, were performed. RESULTS: H&E staining and staining for α-SMA, Ki-67, pSmad2/3 or neural tissue staining showed no differences between TG and wild-type (WT) mice gut tissue. There was increased collagen deposition in the gut of TG mice. Quantitative PCR results of TG gut fibroblasts showed evidence of up-regulated collagen and CTGF transcription, and non-canonical TGF-ß signalling pathways were also up-regulated. The organ bath studies showed diminished colonic strip contractility in TG mice compared with WT control mice to KCl and carbachol. CONCLUSION: We have shown that this TG mouse model, previously shown to develop skin and lung, develops colonic fibrosis with associated effects on colonic tissue contractility. This may offer further insight in pathological processes leading to the development of gut fibrosis.

Propagation of giant migrating contractions between the small intestine, cecum and colon during radiation.

BACKGROUND: Radiation increases the frequency of small intestinal and colonic giant migrating contractions (GMCs). These contractions contribute to the diarrhea and cramping after radiation therapy and are coordinated with one another across the ileocolonic (IC) junction. METHODS: We investigated the coordination of contractile activity between the small intestine, cecum and colon in five canines following circumferential myotomy on the ileum at the IC junction and compared it to intact animals. Studies were performed before and during a radiation schedule. KEY RESULTS: Myotomy increased the frequency of small intestinal GMCs prior to irradiation. In intact animals, the duration and amplitude of cecal GMCs decreased when multiple contractions occurred in rapid succession. This is in contrast to small intestinal and colonic GMCs and suggests a different mechanism of propagation for GMCs within the cecum. Ileal myotomy dramatically decreased the frequency of propagating radiation-induced colonic GMCs. The total number of colonic GMCs was not altered. Colonic contractile activity was disrupted in intact animals during irradiation. However, after ileal myotomy, irradiation did not affect the pattern of colonic contractile states. Diarrhea in irradiated animals with myotomy started earlier than intact animals. This may be related to the frequency of small intestinal GMCs. CONCLUSIONS & INFERENCES: Our findings suggest importance of the enteric neural connections at the IC region to contractile disorders of both the small and large intestine. The anatomic relationship between the canine IC junction is similar to the human ileo-appendiceal-colonic region and surgical manipulations of this area may likewise affect human contractile activity.

micro-Opioid receptor stimulation in the medial subnucleus of the tractus solitarius inhibits gastric tone and motility by reducing local GABA activity.

We examined the effects of altering mu-opioid receptor (MOR) activity in the medial subnucleus of the tractus solitarius (mNTS) on several gastric end points including intragastric pressure (IGP), fundus tone, and the receptive relaxation reflex (RRR). Microinjection of the MOR agonist [d-Ala(2),MePhe(4),Gly(ol)(5)]enkephalin (DAMGO; 1-10 fmol) into the mNTS produced dose-dependent decreases in IGP. Microinjection of the endogenous MOR agonists endomorphin-1 and endomorphin-2 (20 fmol) into the mNTS mimicked the effects of 10 fmol DAMGO. Microinjection of 1 and 100 pmol DAMGO into the mNTS produced a triphasic response consisting of an initial decrease, a transient increase, and a persistent decrease in IGP. The increase in IGP appeared to be due to diffusion to the dorsal motor nucleus of the vagus. The effects of 10 fmol DAMGO in the mNTS were blocked by vagotomy and by blockade of MORs, GABA(A) receptors, and ionotropic glutamate receptors in the mNTS. The RRR response was abolished by bilateral microinjection of the opioid receptor antagonist naltrexone into the mNTS and reduced by intravenous administration of naltrexone. Our data demonstrate that 1) activation of MORs in the mNTS with femtomole doses of agonist inhibits gastric motility, 2) the mechanism of MOR effects in the mNTS is through suppression of local GABA activity, and 3) blockade of MORs in the mNTS prevents the RRR response. These data suggest that opioids play an important role in mediating a vagovagal reflex through release of an endogenous opioid in the mNTS, which, in turn, inhibits ongoing local GABA activity and allows vagal sensory input to excite second-order mNTS neurons.

Disturbed colonic motility contributes to anorectal symptoms and dysfunction after radiotherapy for carcinoma of the prostate.

PURPOSE: To evaluate the role of colonic motility in the pathogenesis of anorectal symptoms and dysfunction after radiotherapy (RT) for carcinoma of the prostate. PATIENTS AND METHODS: Thirty-eight patients, median age 71 (range, 50-81) years with localized prostate carcinoma randomized to one of two radiation dose schedules underwent colonic transit scintigraphy and assessment of anorectal symptoms (questionnaire), anorectal function (manometry), and anal sphincteric morphology (endoanal ultrasound) before and at 1 month and 1 year after RT. RESULTS: Whole and distal colonic transit increased 1 month after RT, with faster distal colonic transit only persisting at 1 year. Frequency and urgency of defecation, fecal incontinence, and rectal bleeding increased 1 month after RT and persisted at 1 year. Basal anal pressures remained unchanged, but progressive reductions occurred in anal squeeze pressures and responses to increased intra-abdominal pressure. Rectal compliance decreased progressively in the patients, although no changes in anorectal sensory function ensued. Radiotherapy had no effect on the morphology of the internal and external anal sphincters. Distal colonic retention was weakly related to rectal compliance at 1 month, but both faster colonic transit and reduced rectal compliance were more frequent with increased fecal urgency. At 1 year, a weak inverse relationship existed between colonic half-clearance time and frequency of defecation, although both faster whole-colonic transit and reduced rectal compliance occurred more often with increased stool frequency. CONCLUSION: Colonic dysmotility contributes to anorectal dysfunction after RT for carcinoma of the prostate. This has implications for improving the management of anorectal radiation sequelae.

Monitorización ambulatoria del pH esofágico con pH-metría sin sonda (sistema Bravo®). Estudio de tolerancia, seguridad y eficacia / Outpatient monitoring of oesophageal pH with a catheter-free pH-meter (Bravo® System). A Study of tolerance, safety and efficacy

Fundamento y objetivo. Recientemente se ha desarrollado un nuevo sistema de pH-metría esofágica ambulatoria sin catéter, el sistema Bravo®. El objetivo de este estudio es comprobar la tolerancia, la seguridad y la eficacia del sistema en la medición del reflujo gastroesofágico, en comparación con la pH-metría convencional. Pacientes y método. El estudio se realizó en un grupo control constituido por 10 voluntarios sanos (grupo 1) y en un grupo de 40 pacientes con síntomas de enfermedad por reflujo gastroesofágico (grupos 2 y 3). A todos los pacientes se les realizó endoscopia digestiva alta, manometría esofágica y pH-metría esofágica convencional y/o pH-metría sin catéter con el sistema Bravo®. Todos los pacientes a los que se realizaron ambas pruebas (grupos 1 y 3) rellenaron un cuestionario sobre molestias físicas y alteraciones de su actividad diaria. Resultados. La tolerancia de la prueba fue mejor con el sistema Bravo® en 9 de los 10 parámetros estudiados. En el grupo de voluntarios sanos (grupo 1), la mediana (intervalo) del porcentaje total de pH < 4 fue del 1,1% (0,5-3,1%) con la pH convencional y el 1,7% (0-3,4%) con el sistema Bravo®. En cuanto a los pacientes con síntomas de enfermedad con reflujo gastroesofágico (grupo 2) a los que se realizó sólo un tipo de pH-metría, el reflujo ácido fue significativamente mayor en los pacientes con esófago de Barrett que en el resto de los grupos, tanto con la pH convencional como con el Bravo®. Si analizamos al grupo de pacientes con enfermedad por reflujo gastroesofágico a los que se realizaron ambas técnicas (grupo 3), 7 de los 10 pacientes tenían un reflujo patológico que sólo se evidenció al realizar pH-metría con el sistema Bravo®. Conclusiones. La pH-metría sin sonda (Bravo®) es mejor tolerada y de mayor satisfacción para los voluntarios sanos y los pacientes que la pH-metría convencional, en ocasiones incluso es más eficaz para el estudio del reflujo ácido por la menor frecuencia de resultados negativos (AU)

Background and objective. A new catheter-free outpatient oesophageal pH-meter system (Bravo®), has recently been developed. The objective of this study is to test the tolerance, safety and efficacy of the system in the measurement of gastric-oesophageal reflux by comparing it with a conventional pH system. Patients and method. The study was performed on a control group consisting of 10 healthy volunteers (group 1) and in a group of 40 patients with symptoms of gastric-oesophageal reflux disease (groups 2 and 3). An upper digestive sytem endoscopy, oesophageal manometry and oesophageal pH measurements with a conventional system and/or with the Bravo® catheter-free system, was performed on all patients. All patients who had both tests done (groups 1 and 2) filled in a questionnaire on any physical problems and changes in their daily activity. Results. The test tolerance was higher with the Bravo® system in the 9 parameters studied. In the group of healthy volunteers (group 1), the median (range) of the total percentage of pH < 4 was 1.1% (0.5-3.1) with the conventional pH and 1.7% (0-3.4) with the Bravo®. When comparing the patients with symptoms of gastric-oesophageal reflux disease (group 2) with those who had only one type of pH measurement made, the acid reflux was significantly higher in patients with Barrett’s oesophagus than in the rest of the groups, with conventional pH as well as with the Bravo®. If we analyse the patient group with disease due to gastric-oesophageal reflux with those on whom both techniques were used (group 3), 7 of the 10 patients had a pathological reflux that only showed up on measuring pH with the Bravo® system. Conclusions. Catheter-free pH measurements (Bravo®) is better tolerated and with better satisfaction for the healthy volunteers and patients than with conventional PH, even, on occasions being more efficient for studying acid reflux due to the lower incidence of negative results (AU)

Effects of radiation upon gastrointestinal motility.

Whether due to therapeutic or belligerent exposure, the gastrointestinal effects of irradiation produce symptoms dreaded by a majority of the population. Nausea, vomiting, diarrhea and abdominal cramping are hallmarks of the prodromal phase of radiation sickness, occurring hours to days following radiation exposure. The prodromal phase is distinct from acute radiation sickness in that the absorptive, secretory and anatomic changes associated with radiation damage are not easily identifiable. It is during this phase of radiation sickness that gastrointestinal motility significantly changes. In addition, there is evidence that motor activity of the gut contributes to some of the acute and chronic effects of radiation.

Roles of muscarinic receptor subtypes in small intestinal motor dysfunction in acute radiation enteritis.

Administration of abdominal radiotherapy results in small intestinal motor dysfunction. We have developed a rat radiation enteritis model that, after exposure in vivo, shows high-amplitude, long-duration (HALD) pressure waves in ex vivo ileal segments. These resemble in vivo dysmotility where giant contractions migrate both antegradely and retrogradely. Mediation of these motor patterns is unclear, although enteric neural components are implicated. After the induction of acute radiation enteritis in vivo, ileal segments were isolated and arterially perfused. TTX, hexamethonium, atropine, or the selective muscarinic antagonists pirenzepine (M(1)), methoctramine (M(2)), and 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP; M(3)) were added to the perfusate. The baseline mean rate per minute per channel of HALD pressure waves was 0.35 +/- 0.047. This was significantly reduced by TTX (83.3%, P < 0.01), hexamethonium (90.3%, P < 0.03), and atropine (98.4%, P < 0.01). The HALD pressure wave mean rate per minute per channel was significantly reduced by pirenzepine (81.1%, P < 0.03), methoctramine (96.8%, P < 0.001), and 4-DAMP (93.1%, P < 0.03) compared with predrug baseline data. As an indicator of normal motility patterns, the frequency of low-amplitude, short-duration pressure waves was also assessed. The mean rate per minute per channel of 5.15 +/- 0.98 was significantly increased by TTX (19%, P < 0.05) but significantly reduced by pirenzepine (35.1%, P < 0.02) and methoctramine (75%, P < 0.0003). However, the rate of small-amplitude pressure waves was not affected by hexamethonium, atropine, or the M(3) antagonist 4-DAMP. The data indicate a role for neuronal mechanisms and the specific involvement of cholinergic receptors in generating dysmotility in acute radiation enteritis. The effect of selective M(3) receptor antagonism suggests that M(3) receptors may provide specific therapeutic targets in acute radiation enteritis.

Rectal morbidity after permanent prostate brachytherapy with dose escalation to biologic target volumes identified by SPECT/CT fusion.

PURPOSE: To evaluate rectal morbidity after dose escalation to biologic target volumes identified by capromab pendetide (ProstaScint) single-photon emission tomography images coregistered with computed tomography (SPECT/CT). METHODS AND MATERIALS: Two hundred thirty-nine consecutive patients diagnosed with T1c-T3b NxM0 adenocarcinoma of the prostate were treated with brachytherapy seed implant (SI) dose escalation to SPECT/CT-identified biologic target volumes, from February 1997 through December 2002. Patients received SI (n=150) or external beam radiation therapy plus SI (n=89). Rectal morbidity was evaluated by clinician scoring using the modified Radiation Therapy Oncology Group criteria. The median followup was 47.2 (range 24.8-96.1) months. RESULTS: The rate of acute Grades I and II toxicity was 29.9% and 3.7%, respectively, and chronic Grade I toxicity was 15.4%, 12.4%, 2.3%, and 1.8% at 1, 2, 3, and 4 years postimplant, respectively. Chronic Grade II toxicities were 1.8%, 1.9%, 1.5%, and 0.9% at 1, 2, 3, and 4 years, respectively. No Grade III rectal toxicity was reported. Chronic Grade IV rectal toxicity was 0.5% and 0.6% at 1.5 and 2.5 years, respectively. Ninety-six percent of patients reported freedom from all rectal toxicity after 3 years. CONCLUSIONS: Dose intensification to occult tumor targets without increasing rectal toxicity may be achieved using SPECT/CT ProstaScint. Additional research to define the role of molecular imaging in prostate cancer is warranted.

Electro-acupuncture attenuates stress-induced defecation in rats with chronic visceral hypersensitivity via serotonergic pathway.

Acupuncture has long been used for patients with irritable bowel syndrome. However, it has remained unclear. The aim of this study was to testify the effect of electro-acupuncture(EA) on (1) visceral hypersensitivity induced by the mechanical colorectal irritation during postnatal development of rats, and (2) stress-induced colonic motility changes on rats with chronic visceral hypersensitivity. The abdominal withdrawal reflex (pain threshold and score) for visceral hypersensitivity and fecal pellet output for motor dysfunction were selected as two indexes for measurement. In addition, the effect of EA on 5-HT(4a) receptor and serotonin transporter (SERT) expression in the colon mucosa was analyzed semi-quantitatively through immunohistochemistry and 5-HT concentration in the colon tissue was observed through spectro-photo-fluorimeter detection, respectively. Our results showed that EA significantly elevated pain threshold, decreased the scores and also decreased fecal pellet output during water avoid stress. Furthermore, EA decreased 5-HT concentration in colon in rats with CVH and CVH rats with water avoidance stress, and increased the 5-HT(4a) and SERT expression in rats with CVH. Thus, it can be concluded that EA attenuates behavioral hyperalgesia and stress-induced colonic motor dysfunction in CVH rats via serotonergic pathway.

Leptin increases small intestinal response to cholecystokinin in leptin-deficient obese mice.

INTRODUCTION: Leptin receptors are present in the jejunum, ileum, and vagal neurons. Leptin increases duodenal secretion of cholecystokinin (CCK) and acts with CCK on vagal mechanoreceptors in the regulation of small intestinal motility. We have demonstrated that leptin-deficient (Lepob) obese mice have increased jejunal and normal ileal responses to CCK. Therefore, we hypothesized that leptin administration alters small intestinal motility observed in leptin-deficient obese mice. MATERIALS AND METHODS: Twelve-week-old female leptin-deficient (Lepob) obese mice received either saline (n=12) or 5 microg/g leptin ip (n=12) injections daily. After 4 weeks, jejunal and ileal segments were harvested, mounted in an organ bath, and reacted with acetylcholine (ACh, 10(-5)M) and CCK (10(-8,-7,-6)M). Data were expressed as N/cm2 and compared by ANOVA and Student's t test. RESULTS: The average body weights in the leptin-treated group were significantly decreased compared to those of the saline-treated group (34 versus 49 g, P <0.01). Jejunal responses to ACh within each group were significantly decreased (P <0.05) when compared to ileal responses. No significant differences in responses to ACh were observed between groups. Jejunal responses to 10(-7,-6)M CCK in the leptin-treated group were significantly greater than those in the saline-treated group. Ileal responses in the leptin group were similarly increased at all CCK concentrations. CONCLUSIONS: These data suggest that daily leptin administration for 4 weeks in leptin-deficient (Lepob) obese mice increases jejunal and ileal responses to CCK and does not alter responses to ACh. Therefore, we conclude that regulation of small intestinal motility may be influenced by synergistic action of cholecystokinin and leptin.

Serotonin involvement in the electroacupuncture- and moxibustion-induced gastric emptying in rats.

OBJECTIVE: Electroacupuncture (EA) as well as moxibustion stimulation has been reported to produce an excitatory effect on the gastrointestinal motility of the rat. Serotonergic neurons of the mioenteric and submucous plexus are major participants in the gastrointestinal physiology. Here, we compared the outcomes of the stimulation of a specific set of acupoints with either acupuncture or moxibustion on the gastrointestinal motility and the role of serotonin (5-HT) in this effect. METHODS: To analyze the role of 5-HT on the gastrointestinal motility of the rat, we studied the flow of 25 glass beads administered to the stomach, after treatment of the animals with a serotonin inhibitor (para-chlorophenylalanine [pCPA]). Acupuncture stimulation was performed on acupoints St-36 (Zusanli) and Sp-6 (Sanyinjiao), with electrical stimulation, or on acupoints Ren-10 (Xiawan), Ren-12 (Zhongwan) and St-25 (Tianshu), with moxibustion. Animals subjected to sham stimulation were used as controls in addition to naive, unstimulated animals. RESULTS: Stimulation of the hind limb (St-36 and Sp-6) and abdominal (Ren-10, Ren-12, St-25) acupoints resulted in effective gastric emptying, as compared with sham-stimulated animals. Pretreatment of animals with pCPA abolished either the response provided by acupuncture stimulation in animal groups subjected to hind limb acupoints or the response provided by moxibustion stimulation in abdominal acupoints. CONCLUSION: Our data suggest that moxibustion in the abdominal points and EA in the hind limb require an intact serotonergic pathway. In addition, we suggest that this involvement of serotonin is a general feature of the mediated effects of acupuncture on gastric emptying of the rat.

Anorectal dysfunction increases with time following radiation therapy for carcinoma of the prostate.

OBJECTIVES: To characterize the prevalence and pathophysiology of anorectal dysfunction up to 2 yr following radiation therapy (RT) for localized carcinoma of the prostate. METHODS: Thirty-eight patients, median age 68 (range 60-82) yr with localized prostate carcinoma randomly assigned to one of two radiation dose schedules, underwent evaluation of the following variables of anorectal function before RT, as well as 4-6 wk and 1 and 2 yr after its completion: (1) symptoms, (2) anorectal motility, (3) anorectal sensory function, and (4) anal sphincteric morphology. RESULTS: There was a persistent increase in anorectal symptoms after RT. At 2 yr, bowel frequency, urgency, and fecal incontinence were increased in 50%, 47%, and 26% of patients, respectively. After RT, there were progressive reductions of (1) basal anal pressures, (2) anal pressures in response to squeeze and increased intra-abdominal pressure, (3) rectal compliance, and (4) rectal volumes associated with sensory perception and the desire to defecate. The thickness of the external anal sphincter increased with time after RT. No difference was observed between the patients in the two radiation dose schedules. CONCLUSIONS: Anorectal dysfunction following RT for prostate carcinoma is an underestimated cause of morbidity, which progresses with time. The prevalence and pathophysiology of anorectal dysfunction is similar after treatment with two commonly used radiation dose schedules.

Involvement of primary afferent nerves after abdominal irradiation: consequences on ileal contractile activity and inflammatory mediator release in the rat.

In this study we analyzed the role of substance P (SP) from afferent nerves in ileum contractibility and in the release of inflammatory mediators (neurotensin, Il-1beta, and TNF-alpha) in ileal mucosa and muscularis layers after a 10-Gy gamma-irradiation of the abdomen. Six hours after irradiation, SP concentrations were lower than in control rats, and 3 days after irradiation SP-induced contractile activity was higher. Irradiation significantly increased the levels of neurotensin, Il-1beta, and TNF-alpha in both layers. Pretreatment with capsaicin depleted afferent nerve endings of SP and reduced SP levels by about 50%. Capsaicin treatment reduced SP concentrations further, beyond the levels due to irradiation, thereby suggesting that all sources of SP are affected by irradiation. Capsaicin treatment prevented the irradiation from affecting SP-induced contractile response or increasing neurotensin levels. This finding suggests that SP released by afferent nerve endings controls these functions. Proinflammatory cytokine release was not reduced by capsaicin treatment.

Effects of lumbar skin warming on gastric motility and blood pressure in humans.

We examined the possibility that lumbar skin warming can increase gastrointestinal motility by investigating the electrogastrogram (EGG), blood pressure, and heart rate with psychometric ratings in healthy humans. Scores of mood state profiles showed that lumbar skin warming (42 degrees C, 20 min) decreased tension-anxiety, depression, anger-hostility, fatigue, and confusion of the participants. A multiple bandpass filter analysis of EGGs showed that a postural transition from orthostatic to supine for measurement caused an increase in dominant frequency of 25-29% towards the frequencies of the normal interdigestive migrating motor complex (IMC). The spectral power of the IMC band, 2.55-3.05 cycles/min, was increased by 20 min-warming, reflecting the increase in gastric contractility. No increase in the spectral power was observed in the time-matched control group without skin warming. Therefore, an increase in contractility is a characteristic of lumbar skin warming. The systolic blood pressure increased by 15% during warm stimulation. Interbeat intervals were not influenced by warm stimulation. An analysis of interbeat intervals by a fast Fourier transform method showed that the cardiac sympathetic and parasympathetic nerves did not play a major role in raising the blood pressure. Vasoconstriction of the mesenteric artery was therefore considered to cause a blood pressure increase during warming. It is hypothesized that vasoconstriction of the visceral arteries by lumbar skin warming increases the blood pressure and gastrointestinal contractility.

Single millimeter wave treatment does not impair gastrointestinal transit in mice.

Millimeter wave treatment (MWT) is based on those biological effects that develop following skin exposure to low power electromagnetic waves. This method of treatment is in wide clinical use in several Eastern European countries for treatment of a variety of conditions, including pain syndromes. However, most treatment modes of MWT were developed empirically, and certain indications and contraindications for the use of MWT remain to be established. In our previous blind experiments we have shown that the hypoalgesic effect of MWT may be quantitatively evaluated, and most probably mediated by the neural system in general, and the system of endogenous opioids in particular. Taking in consideration a well-known ability of opioids to cause gastrointestinal disturbances, which could limit clinical application of MWT, the main aim of the present study was to investigate whether a single MWT, that can produce opioid-related hypoalgesia, may also retard gut transit and colorectal passage in mice. The charcoal meal test was used to quantitatively evaluate upper gastrointestinal transit, and the glass bead test was employed to examine colonic propulsion in mice. MWT was applied to the nose area of mice. The MWT characteristics were: frequency = 61.22 GHz; incident power density = 15 mW/cm(2); and duration = 15 min. The results obtained have shown that MWT does not significantly change small intestinal or colonic transit in mice, and thus suppression of gastrointestinal motility should not be a setback in the clinical use of MWT.