Defecation Reflex Research Articles

Interpretation of Chinese guidelines for the diagnosis and treatment of constipation surgery (2017)

The Chinese Society of Coloproctology (CSCP) released the updated "guidelines for the diagnosis and treatment of constipation surgery" in 2017. The major amendments include the following aspects: (1) According to defecation reflex involving parts of the classification, the cause of constipation is divided into three parts, including colorectal factors, internal and external colorectal factors. The new division is more rational, easy to make clear the location and the possible pathogenesis. (2) Constipation is divided into slow transit constipation, outlet obstructive constipation and mixed constipation. The main consideration of this division is the name of the surgery for the outlet obstructive constipation, such as the rectal prolapse and the rectocele. (3) The 6-hour observation time point is added in the colonic transit test and to make clear whether the stomach and the small intestine has slow transit. (4) Micro ecological preparations, promoting dynamic drugs and promoting secretion drugs as well as psychological treatment and acupuncture treatment are added in non-surgical treatment of constipation (5) The antegrade colonic enema is removed from surgical treatment of slow transit constipation; in the surgical treatment of internal rectal prolapse, STARR surgery is added and Delorme surgery is deleted; transrectal and transperineal approach are added in the surgical treatment of rectocele. In this paper, we compare the domestic and international constipation-related guidelines, and summarize the main revisions in the 2017 edition of "guidelines for the diagnosis and treatment of constipation surgery".

Opioid induced constipation in cancer patients: pathophysiology, diagnosis and treatment

ABSTRACTOpioid-induced constipation (OIC) has emerged as a major contributor to morbidity in cancer patients. OIC is common, difficult to treat and causes significant reductions in the quality-of-life of cancer patients. It results from opioid action on gut mu-receptors, which leads to the disruption of bowel motility, mucosal transport and defecation reflexes. Laxatives are cornerstone in the management of OIC despite their relatively limited effectiveness and lack of strong evidence supporting their use. In the past few years, novel therapeutics have emerged for the management of OIC. These include; prokinetic agents, peripherally-acting mu-opioid receptor antagonists (PAMORAs), secretagogues and opioid receptor agonist/antagonist combination tablets. This article will review the mechanism of OIC in cancer patients and describe the novel therapeutic options for its prevention and management.

Ghrelin receptors as targets for novel motility drugs.

Constipation arises from a multitude of causes, including aging, spinal cord injury (SCI), and dietary issues. The heterogeneity of inciting factors has made the treatment of constipation particularly challenging. Agonists of ghrelin receptors have beneficial effects on delayed gastric emptying, but less is known about their ability to improve colorectal motility. Recent publications indicate that the activation of the ghrelin receptors in the spinal cord can alleviate constipation due to dietary causes, Parkinsonism, and SCI in rodents. Ghrelin-responsive neurons in the intermediolateral cell column of the lumbosacral spinal cord can activate enteric microcircuits that coordinate propulsive colorectal contractions, leading to defecation. Learning more about the properties of neurons in the spinal defecation center and the roles of ghrelin receptors in the defecation reflex will accelerate the development of improved treatments of constipation.

Safety and usefulness of Laghu shankha prakshalana in patients with essential hypertension: A self controlled clinical study.

Background:Yoga and Ayurveda texts emphasize the role of cleansing the bowel as an important component of management of hypertension (HTN). Observations during our clinical experience and pilot studies on Laghu shankha prakshalana kriya (LSP), a yogic bowel cleansing technique, appeared to be safe and complimentary.Objective:To test the safety and effectiveness of LSP in patients with essential hypertension.Materials and Methods:This self control study recruited 32 patients with mild to moderate essential HTN admitted for a week long residential integrated yoga therapy program at the integrative health home in Bengaluru. Patients had a daily routine of 6 hours of integrated approach of yoga therapy (IAYT) module for HTN that included physical postures, relaxation sessions, pranayama and meditations. LSP, an additional practice, that involved drinking of luke-warm water (with or without a herbal combination, triphala) followed by a set of specific yoga postures that activates defecation reflex, was administered on 2nd (LSP without triphala) and 5th day (LSP with triphala). Assessments (sitting blood pressure and pulse rate) were done just before and after both the sessions of LSP. Secondary outcome measures such as body mass index (BMI), symptom scores, medication scores, fatigue, state and trait anxiety, general health and quality of life were assessed on 1st and 6th day of IAYT intervention.Results:There was significant (P < 0.001, paired t test) reduction in blood pressure (systolic and diastolic) and pulse rate immediately after both the sessions (LSP with and without triphala). There were no adverse effects reported during or after LSP. There was no significant difference between the two techniques (P < 0.505, independent samples t test), although the percentage change appeared to be higher after triphala LSP session. The number of visits to clear the bowel during the procedure was significantly (P < 0.001, independent samples t test) higher after LSP with triphala than LSP without triphalā. After weeklong IAYT, there were significant reductions in blood pressure (P < 0.001), BMI (P < 0.004), medication score (P < 0.001), symptoms score (P < 0.001), fatigue (P < 0.001), state and trait anxiety (STAI, P < 0.001), scores of general ill health (GHQ, P < 0.001), and increase in comfort level (P < 0.001) and quality of sleep (P < 0.001).Conclusion:LSP (a part of IAYT) is a safe and useful procedure for patients with essential hypertension. LSP with triphala is more useful.

Impact of disrupting adenosine A3 receptors (A3−/−AR) on colonic motility or progression of colitis in the mouse

Pharmacological studies suggest that adenosine A₃AR influences motility and colitis. Functional A₃⁻/⁻AR knockout mice were used to prove whether A₃AR activation is involved in modulating either motility or colitis. A₃AR was probed by polymerase chain reaction (PCR) genotyping, Western blot, and immunochemistry. Motility was assessed in vivo by artificial bead-expulsion, stool-frequency, and FITC-dextran transit. Colitis was induced with dextran sodium sulfate (DSS) in A₃⁻/⁻AR or wildtype (WT) age- and sex-matched controls. Progression of colitis was evaluated by histopathology, changes in myeloperoxidase (MPO), colon length, CD4(+) -cells, weight-loss, diarrhea, and the guaiac test. Goat anti-hu-A₃ antiserum identified a 66 kDa immunogenic band in colon. A₃AR-immunoreactivity is expressed in SYN(+) -nerve varicosities, s-100(+) -glia, and crypt cells, but not 5-HT(+) (EC), CD4(+) (T), tryptase(+) (MC), or muscle cells. A₃AR immunoreactivity in myenteric ganglia of distal colon >> proximal colon by a ratio of 2:1. Intestinal transit and bead expulsion were accelerated in A₃⁻/⁻AR mice compared to WT; stool retention was lower by 40%-60% and stool frequency by 67%. DSS downregulated A₃AR in epithelia. DSS histopathology scores indicated less mucosal damage in AA₃⁻/⁻AR mice than WT. A₃⁻/⁻AR phenotype protected against DSS-induced weight loss, neutrophil (MPO), or CD4(+) -T cell infiltration, colon shortening, change in splenic weight, diarrhea, or occult-fecal blood. Functional disruption of A₃AR in A₃⁻/⁻AR mice alters intestinal motility. We postulate that ongoing release of adenosine and activation of presynaptic-inhibitory A₃AR can slow down transit and inhibit the defecation reflex. A₃AR may be involved in gliotransmission. In separate studies, A₃⁻/⁻AR protects against DSS colitis, consistent with a novel hypothesis that A₃AR activation contributes to development of colitis.

Effect of the artificial somato-autonomic neuroanastomosis on defecation after spinal cord injury and its underlying mechanisms

Objective A new artificial somatic-autonomic neuroanastomosis has been established in male rats with spinal cord injury (SCI). Anorectal manometry and neural retrograde tracing were conducted in such animal model after establishing the regenerated reflex pathway to analyze the mechanisms,and the effects on restoring anorectal function and rectum external sphincter synergetic status. Methods In normal male Sprague-Dawley rats weighing 280-300 g, under anesthesia the rats were subjected to limited laminectomy of L4-L6 vertebrae to expose the spinal cord, and the new reflex pathways were established by intradural microanastomosis of left L4 ventral root to the L6 ventral root while leaving the L4 dorsal root intact to trigger the new defecation reflex pathway. Then L4VR-L6VR formed the foreign nerve root. Three months later the spinal cord was completely transected at the T9-10 level. Eight weeks later the model rats were randomly divided into two groups (n1=8,n2=4). The rats in the group 1 were applied in anorectal manometry, and those in the group 2 for neural retrograde tracing study. Results Stimulation of the L4VR proximal end to the anastomosis and the left sciatic nerve induced rectum to contract, and simultaneously greatly weakened electric activity of external anal sphincter (EAS) ( indicating synergetic relaxation of EAS). But stimulation of the contralateral L6VR evoked simultaneous contraction of rectum and EAS. After FG was injected into the left major pelvic ganglia (MPG) and TMR into the EAS, FG-TMR dual labeled neurons and FG or TMR single labeled neurons were mainly observed in the angulus anterior of L4segment in the model rats. FG-TMR positive neurons were not observed in the spinal cord of the normal rats. Conclusion After establishment of the artificial somato-autonomic neuroanastomosis the regenerated neural pathways can effectively improve the rectum EAS synergetic status and restore the anorectal function.Simultaneous reinnervation of MPG and EAS by one group of the dual labeled neurons in L4 may be the key neural anatomy infrastructure for controllable defecation via the somatic-autonomic reflex pathway. Key words: Somato-autonomic neuroanastomosis; Spinal cord injury; Synergetic defecation

A 5-HT4-receptor activation-induced neural plasticity enhances in vivo reconstructs of enteric nerve circuit insult

It was recently reported that some 5-HT(4)-receptor agonists increased neuronal numbers and length of neurites in enteric neurons developing in vitro from immunoselected neural crest-derived precursors. We aimed to explore a novel approach in vivo to reconstruct the enteric neural circuitry that mediates a fundamental distal gut reflex. The neural circuit insult was performed in guinea pigs by rectal transection and subsequent end-to-end one layer anastomosis. A 5-HT(4)-receptor agonist, mosapride citrate (10-100 micromol L(-1)) (applied for a patent) was applied locally at the anastomotic site. Mosapride promoted the regeneration of the neural circuit in the impaired myenteric plexus and the recovery of the defecation reflex in the distal gut. Furthermore, mosapride generated neurofilament (NF)-, 5-HT(4)-receptor- and 5-bromo-2'-deoxyuridine (BrdU)-positive cells and surprisingly formed neural network in the newly formed granulation tissue at the anastomotic site 2 weeks after enteric nerve circuit insult. Possible neural stem cell markers, anti-distal less homeobox 2 (DLX2)- and p75-positive and NF-positive cells increased during the same time period. All actions by mosapride were inhibited by the specific 5-HT(4)-receptor antagonist, GR113808 (10 micromol L(-1)). These results indicate that activation of enteric neural 5-HT(4)-receptors promotes reconstruction of an enteric neural circuit leading to the recovery of the defecation reflex in the distal gut, and that this reconstruction involves possibly neural stem cells. These findings indicate that treatment with 5-HT(4) agonists could be a novel therapy for generating new enteric neurons to rescue aganglionic gut disorders.

The plasticity of the defecation reflex pathway in the enteric nervous system of guinea pigs

The enteric nervous system, the "second" brain, is an independent nervous system that structurally resembles the "first" brain. Appropriate rectal distension elicits rectal (R-R) reflex contractions and simultaneous internal anal sphincter (R-IAS) reflex relaxations that together comprise the defecation reflex. The enteric nervous system, pelvic nerves and lumbar colonic nerves control both reflexes. Using the plasticity of enteric nervous pathways, a new therapy for repairing enteric neural dysfunction could be developed. In vivo experiments were performed on guinea pigs anesthetized with ethyl carbamate. We performed either a lower anterior resection as used for rectal cancer, without damaging the extrinsic nerves or a resection of a 2-cm segment of distal colon, 30 mm orally from the anal verge, with subsequent end-to-end one layer anastomosis of the exposed ends. The recovery of the defecation reflex was found to be the same in both the rectal transection and distal colonic resection procedures. Eight weeks after sectioning the intrinsic reflex nerve pathways in the rectum, the defecation reflex recovered to control levels, accompanied by a regeneration of the reflex pathways. The 5-HT(4) receptor agonist, mosapride (0.5 and 1.0 mg/kg), significantly (P<0.01) enhanced the recovered defecation reflex at this stage. Two weeks after local treatment with brain-derived neurotrophic factor (BDNF: 10(-6) g/ml) at the rectal anastomotic site, the R-IAS reflex relaxations recovered and some bundles of fine nerve fibers were able to be seen interconnecting the oral and anal ends of the myenteric plexus. Also surprisingly, new neurons were found to have generated from neural stem cells at the anastomotic ends. These new neurons had constructed mature enteric neural networks including ganglionic-like structures eight weeks after surgery. These results revealed the plasticity of enteric neurons, allowing the proposal of a new therapy for repairing enteric neural dysfunction at least after surgery.

A new possibility for repairing the anal dysfunction by promoting regeneration of the reflex pathways in the enteric nervous system

Moderate rectal distension elicits recto-rectal reflex contractions and simultaneous recto-internal anal sphincter reflex relaxations that together comprise the defecation reflex. Both reflexes are controlled by 1) pelvic nerves, 2) lumbar colonic nerves, and 3) enteric nervous system. The aim of the present study was to explore a novel approach to repairing the defecation reflex dysfunction by using the plasticity of enteric nervous pathways. Experiments were performed in anesthetized guinea pigs with ethyl carbamate. The rectum 30 mm oral from the anal verge was transected without damage to extrinsic nerves, and subsequent end-to-end one-layer anastomosis was performed. Recovery of the defecation reflex and associated reflex pathways were evaluated. Eight weeks after sectioning of intrinsic reflex nerve pathways in the rectum, the defecation reflex recovered to the control level, accompanied with regeneration of reflex pathways. The 5-HT(4)-receptor agonist mosapride (0.5 and 1.0 mg/kg) significantly (P < 0.01) enhanced the recovered defecation reflex 8 wk after surgery. Two weeks after local treatment with brain-derived neurotrophic factor (BDNF: 10(-6) g/ml) at the rectal anastomotic site, the recto-internal anal sphincter reflex relaxations recovered and some bundles of fine nerve fibers were shown to interconnect the oral and anal ends of the myenteric plexus. These results suggested a possibility for repairing the anal dysfunction by promoting regeneration of the reflex pathways in the enteric nervous system with local application of BDNF.

BDNF-induced facilitation on regeneration of enteric nerve pathways for the defecation reflex in guinea pigs

Moderate rectal distension elicits rectal reflex contractions and simultaneous internal anal sphincter reflex relaxations, composed of defecation reflex. Both reflexes are controlled by (1) sacral excitatory reflexes mediated via pelvic nerves, (2) lumbar inhibitory reflexes mediated via lumbar colonic nerves, which are suppressed by pontine defecation reflex center, (3) intrinsic reflexes mediated via enteric nervous system. The plasticity of the intrinsic reflex pathway has been shown in the guinea pig that underwent chronic destruction of lumbar and sacral cords as follows: after removal of extrinsic reflex pathways, unchanged recto-rectal (R-R) reflex contractions and synchronous recto-IAS (R-IAS) reflex relaxations occurred, indicating intrinsic reflexes are able to compensate the defect of extrinsic reflex pathways.

Diagnosis and treatment of pediatric anismus

To explore the diagnosis and treatment methods of pediatric anismus. Twenty-nine patients with idiopathic chronic constipation, diagnosed with anismus by colon barium contrast and anorectal manometry from Nov. 2001 to Nov. 2004 in our hospital, were investigated retrospectively. This group consisted of 13 men and 16 women whose mean age was (6.7+/-4.0) years. Hirschsprung diseases were excluded from the patients by colon barium contrast and rectoanal inhibitory reflex (RAIR) examination. Normal RAIR (5-10 ml elicited) was showed on 21 cases while weakened RAIR (15-30 ml elicited) was showed on 8 cases. After the diagnosis, the patients were treated by toilet training, diet regulation and laxative for 1-2 months. 4 cases were recovered, 5 cases were improved and 20 cases were relied on glycerin suppository. Four cases, relied on glycerin suppository, underwent Lynn procedure and had good results after 5-24 months follow-up. Two cases were re-examined by anorectal manometry 3 and 6 months after surgery, the resting pressure and the high pressure zone (HPZ) decreased, but the simulation defecation reflex was still abnormal. The diagnosis of pediatric anismus relies on history of constipation, combined with anorectal manometry and colon barium contrast. Lynn procedure could be chosen for the patients unsatisfied in toilet training and other non-operative treatment.

Pharmacological and Pharmacokinetic Aspects of Functional Gastrointestinal Disorders

Medications are commonly used for the treatment of patients with functional gastrointestinal disorders. The general goal of this report is to review the pharmacokinetics and pharmacology of medications used in functional gastrointestinal disorders. Methods included literature review, consensus evaluation of the evidence for each topic assigned originally to 1 or 2 authors, and broader review at a harmonization session as part of the Rome III process. This report reviews the animal models that have been validated for the study of effects of pharmacologic agents on sensation and motility; the preclinical pharmacology, pharmacokinetics, and toxicology usually required for introduction of novel therapeutic agents; the biomarkers validated for studies of sensation and motility end points with experimental medications in humans; the pharmacogenomics applied to these medications and disorders; and the pharmacology of agents that are applied or have potential for treatment of functional gastrointestinal disorders, including psychopharmacologic agents. Clinician and basic investigators involved in the treatment or investigation of functional gastrointestinal disorders or disease models need to have a comprehensive understanding of a vast range of medications. It is anticipated that the interaction between investigators of basic science, basic and applied pharmacology, and clinical trials will lead to better treatment of these disorders.

Enhancement of the intrinsic defecation reflex by mosapride, a 5-HT4 agonist, in chronically lumbosacral denervated guinea pigs

The defecation reflex is composed of rectal distension-evoked rectal (R-R) reflex contractions and synchronous internal anal sphincter (R-IAS) reflex relaxations in guinea pigs. These R-R and R-IAS reflexes are controlled via extrinsic sacral excitatory nerve pathway (pelvic nerves), lumbar inhibitory nerve pathways (colonic nerves) and by intrinsic cholinergic excitatory and nitrergic inhibitory nerve pathways. The effect of mosapride (a prokinetic benzamide) on the intrinsic reflexes, mediated via enteric 5-HT(4) receptors, was evaluated by measuring the mechanical activity of the rectum and IAS in anesthetized guinea pigs using an intrinsic R-R and R-IAS reflex model resulting from chronic (two to nine days) lumbosacral denervation (PITH). In this model, the myenteric plexus remains undamaged and the distribution of myenteric and intramuscular interstitial cells of Cajal is unchanged. Although R-R and R-IAS reflex patterns markedly changed, the reflex indices (reflex pressure or force curve-time integral) of both the R-R contractions and the synchronous R-IAS relaxations were unchanged. The frequency of the spontaneous R and IAS motility was also unchanged. Mosapride (0.1-1.0 mg/kg) dose-dependently increased both intrinsic R-R (maximum: 1.82) and R-IAS reflex indices (maximum: 2.76) from that of the control (1.0) 6-9 days following chronic PITH. The dose-response curve was similar to that in the intact guinea pig, and had shifted to the left from that in the guinea pig after acute PITH. A specific 5-HT(4) receptor antagonist, GR 113808 (1.0 mg/kg), decreased both reflex indices by approximately 50% and antagonized the effect of mosapride 1.0 mg/kg. This was quite different from the result in the intact guinea pig where GR 113808 (1.0 mg/kg) did not affect either of the reflex indices. The present results indicate that mosapride enhanced the intrinsic R-R and R-IAS reflexes and functionally compensated for the deprivation of extrinsic innervation. The actions of mosapride were mediated through endogenously active, intrinsic 5-HT(4) receptors which may be post-synaptically located in the myenteric plexus of the anorectum.

Functional activity of the rectum: A conduit organ or a storage organ or both

To investigate whether the degree of rectal distension could define the rectum functions as a conduit or reservoir. Response of the rectal and anal pressure to 2 types of rectal balloon distension, rapid voluminous and slow gradual distention, was recorded in 21 healthy volunteers (12 men, 9 women, age 41.7 +/- 10.6 years). The test was repeated with sphincteric squeeze on urgent sensation. Rapid voluminous rectal distension resulted in a significant rectal pressure increase (P < 0.001), an anal pressure decline (P < 0.05) and balloon expulsion. The subjects felt urgent sensation but did not feel the 1st rectal sensation. On urgent sensation, anal squeeze caused a significant rectal pressure decrease (P < 0.001) and urgency disappearance. Slow incremental rectal filling drew a rectometrogram with a "tone" limb representing a gradual rectal pressure increase during rectal filling, and an "evacuation limb" representing a sharp pressure increase during balloon expulsion. The curve recorded both the 1st rectal sensation and the urgent sensation. The rectum has apparently two functions: transportation (conduit) and storage, both depending on the degree of rectal filling. If the fecal material received by the rectum is small, it is stored in the rectum until a big volume is reached that can affect a degree of rectal distension sufficient to initiate the defecation reflex. Large volume rectal distension evokes directly the rectoanal inhibitory reflex with a resulting defecation.

PSEUDODIARRHEA CAUSED BY VAGINAL PESSARY IN AN ELDERLY PATIENT

To the Editor: Diarrhea and fecal incontinence are common complaints in the geriatric population and are often challenging to evaluate and manage. We report here an obscure cause of diarrhea in an older woman that may be more common than realized and easily missed by physicians. An independent 94-year-old woman with a history of hypothyroidism, paroxysmal atrial fibrillation, and vaginal prolapse following a prior hysterectomy presented to the emergency department with weakness, lightheadedness, and 1 day of intractable, frequent bowel movements. The patient reported severe fecal urgency, with small bowel movements occurring every 10 minutes. She denied a history of recent constipation, abdominal pain, hematochezia, fever, or melena. She noted changes in her bowel movements consisting of occasional episodes of mild diarrhea dating back 6 months but no prior episode as severe as this one. These episodes had been investigated on an outpatient basis, with prior stool studies negative for clostridium difficile toxin, and a colonoscopy, which revealed only mild left-sided diverticuli. Upon admission, the patient was found to be in atrial fibrillation. Her serum electrolytes, thyroid tests, complete blood count, cardiac enzymes, and liver function tests were all normal. Her physical examination was unremarkable except for a hard extrinsically protruding object detected on digital rectal examination. This object turned out to be a vaginal pessary, placed approximately 8 months before for treatment of urinary incontinence. A radiograph of the patient's abdomen demonstrating the location of the device is shown in Figure 1. X-ray demonstrating the position of the vaginal pessary. Upon removal of the pessary, the patient's symptoms resolved. We have presented a case of fecal urgency, loose bowel movements, and incontinence caused by a vaginal pessary in an elderly woman. To our knowledge, there is only one other report in the literature of such an occurrence.1 There are several mechanisms by which this patient's symptoms may have been produced. First, the force of the pessary pressing on the rectal mucosa may have caused obstruction with paradoxical diarrhea, as occurs with fecal impaction. Secondly, when the pessary exerted pressure on normal anatomical features, such as the internal and external anal sphincter muscles, it might have stretched the anatomy and altered the normal mediators of fecal continence. Lastly, the presence of the pessary might have produced the sensation of full rectum, elucidating a defecation reflex. The patient in this case had “pseudodiarrhea,” which is defined as increased stool frequency (>3 daily) with a normal daily stool weight of less than 300 g. Conditions commonly associated with pseudodiarrhea include paradoxical diarrhea secondary to fecal impaction and irritable bowel syndrome. Physicians should be aware that there are many different symptoms that patients term as “diarrhea,” and these should be differentiated in the history taking. They include fecal incontinence, urgency, liquidity of the stool, frequency, and volume of stool. Patients are likely to define diarrhea as stool liquidity. The strict scientific definition of diarrhea is stool quantity greater than 300 g/d, although most clinicians generally also consider increased stool frequency (>3/d) as part of the definition.2

The defecation reflex in rats: fundamental properties and the reflex center

While pharmacological and physiological studies in rats are now increasing, physiological properties of their defecation have been scarcely investigated. This study was performed to define the properties of defecation in decerebrate rats, with special reference to the pontine defecation reflex center, which has been postulated in dogs. Intraluminal pressure was recorded from the colon and rectum with balloon-pressure transducer method using balloons of 15–20 mm in length and 0.1–0.3 ml in volume. Distention of a balloon in the descending colon and rectum with an additional injection of 0.03–0.1 ml air induced propulsive contractions on the descending colon and rectum. The mean of threshold pressures to induce propulsive contraction was 17.0±5.8 mm Hg (mean±S.E.) in the proximal part and 18.3±3.3 mm Hg in the distal part of the descending colon, and 11.8±1.3 mm Hg in the rectum. The maximum amplitude of propulsive contractions was 55 mm Hg in the rectum, 47 mm Hg in the distal part of the descending colon and 38 mm Hg in the proximal part. Similar colorectal propulsive contractions were produced by gastric distention (5–10 ml, 20–30 mm Hg) and electrical stimulation of the anal canal. Contrarily, spontaneous contractions of the proximal colon were suppressed by rectal distention and anal-canal stimulation. These results suggest that the descending colon and rectum, but not the proximal colon, were innervated by the pelvic afferent and efferent fibers mediating the defecation reflex. Pontine transection at the cerebellar peduncle level abolished colorectal propulsive contractions induced by distention of the stomach, descending colon and rectum, and stimulation of the anal canal, although much smaller contractions were still induced after the pontine transection. These results suggest that the pontine defecation reflex center exists and works in rats, as in dogs.

Excitatory neurotoxic properties of pontamine sky blue make it a useful tool for examining the functions of focal brain parts.

Pontamine sky blue (PSB) is used in brain studies to mark the position of microelectrode and micropipette tips. However, few studies have been made on the effects of PSB on neurons; therefore we examined these effects. When puffed on isolated sensory ganglion cells of rats, PSB increased membrane conductance, depolarized membrane potential, and reduced the amplitude of action potentials. When dripped on frog sympathetic ganglion, much like hexamethonium, PSB decreased the amplitude of compound action potentials of the postganglionic strand. A bath application of PSB to sartorius muscle fibers that had been treated with tetrodotoxin depolarized the membrane potential and increased the frequency and amplitude of miniature end-plate potentials. All these effects were reversible. When injected into the rat's pontine part corresponding to the location of the canine pontine defecation reflex center, PSB produced repetitive colorectal contractions and irreversibly abolished them in response to anal-canal stimulation. The excitatory and blocking effects of PSB and its staining ability make it a useful tool for examining the functions of focal brain parts.

Constipation--modern laxative therapy.

It is estimated that one third of the population in Western industrial countries suffers from constipation at least from time to time. Constipation may have somatopathic or functional causes. Furthermore, a great number of substances are known to cause medication-induced constipation, i.e. opioid-induced constipation is caused by linkage of the opioid to opioid receptors in the bowel and the central nerve system. Whenever possible, causal therapy should be undertaken. Patients in palliative care mostly suffer from chronic functional constipation. The treatment consists of basic measures and the application of laxatives. According to their mode of action, they are divided into bulk-forming laxatives, osmotic laxatives, stimulant laxatives, lubricating agents and others. Bulk-forming laxatives are not recommended for use in palliative care patients, for such patients are normally not able to take in the required amount of fluids. Osmotic laxatives are divided into (magnesium) salts, saccharine, alcohols and macrogols. Lactulose is the most popular saccharine laxative. Because of its side effects (flatulence, bloating and abdominal cramping), lactulose is not a laxative of our choice; instead, we prefer to give macrogol. Orally administered, macrogol is not metabolised and pH value and bowel flora remain unchanged. Macrogol hydrates hardened stools, increases stool volume, decreases the duration of colon passage and dilates the bowel wall that then triggers the defecation reflex. Even when given for some time, the effectiveness of macrogol will not decrease. Because of its high effectiveness and commonly good tolerance, macrogol has become the laxative of first choice in palliative care patients with all kinds of chronic constipation, if these patients are able to take in the necessary amount of fluids. From the general medical point of view, lubricating agents have become obsolete. In palliative care patients, however, they are still important laxatives for prophylactic treatment or therapy of constipation. Due to clinical experience, in palliative care a laxative ladder has proven successful.

Study of the role of the second defecation reflex: anorectal excitatory reflex in the pathogenesis of constipation.

Previous studies have shown that anal distension caused rectal contraction, an action mediated through the anorectal excitatory reflex. Anal anesthetization aborted rectal contraction and rectal evacuation was induced by excessive straining. We investigated the hypothesis that inhibition or absence of the anorectal excitatory reflex could lead to constipation. We studied 18 patients (mean age +/- SD: 40.6 +/- 5.8 years, 14 women) with rectal inertia, 14 (41.7 +/- 6.6 years, 12 women) with puborectalis paradoxical syndrome, and 10 healthy volunteers (37.9 +/- 4.8 years, 8 women). The rectum was filled with normal saline until urge and then evacuated; residual fluid was calculated. The anal and rectal pressure response to anal balloon distension in increments of 2 mL of saline was recorded by a two-channel microtip catheter. In the healthy volunteers, saline was evacuated as a continuous stream without straining except occasionally at the start of evacuation; no residual fluid was encountered. Anal balloon distension effected notable rectal pressure increase. In rectal inertia patients, evacuation occurred in small fluid gushes produced with excessive straining; residual fluid of large volume was collected. Anal balloon distension up to 10 mL produced no notable rectal pressure changes. The patients with PPS failed to evacuate more than a few mL of fluid despite excessive straining; the volume of residual fluid was considerable. Anal balloon distension caused a notable rectal pressure rise. The results were reproducible. These results suggest that the defecation reflexes (rectoanal and anorectal) are absent in rectal inertia patients and this presumably denotes a neurogenic disorder. The anorectal reflex is active in puborectalis paradoxical syndrome, but the rectoanal reflex is not, indicating a possible myogenic defect in the puborectalis muscle.

The role of the rectal branches of pelvic plexus in defecation and colonic motility in a canine model.

The parasympathetic nerves regulate colonic motility and defecation. The vagal nerve controls the right colon and the pelvic nerve permeates the left colon and rectum via the rectal branches of the pelvic plexus (RBPP). This investigation aimed to measure the functional changes of the colon and rectum after RBPP-transection for over six months. RBPP-transection was performed in 15 dogs. Five dogs each were sacrificed immediately, one month, and six months after RBPP-transection. The stool condition, colorectal transit, defecation reflex, colorectal response to electrical stimulation, and pathological degeneration was investigated prior to, one month after, and six months after RBPP-transection. Four of the 5 dogs observed had loose stool one month after RBPP-transection, and one of the 3 had recovered six months later. Half transit time (HTT) at transverse colon got longer in six of the 8 in one month. Six months later, HTT got shorter in three of the 4 than that of one month. Defecation reflex was not observed one month after RBPP-transection, but noted in two of the 5 six months later. These results may suggest that vagal nerve compensates for the oral site of the left colon after denervation of the pelvic nerve which is originally distributed.