Relaxation Of Internal Anal Sphincter Research Articles

Rectoanal reflex parameters in incontinence and constipation.

The transient relaxation of the internal anal sphincter in response to rectal distention is believed to play an important role in the continence mechanism. Most anorectal physiology laboratories merely report the rectoanal inhibitory reflex as being either present or absent. This study aimed to assess the parameters of the rectoanal inhibitory reflex in incontinent and constipated patients and healthy control subjects, in an attempt to analyze differences in internal anal sphincter function in these groups. We analyzed each response of the internal anal sphincter to rectal distention with progressively increasing volumes of air at a single site (proximal anal canal). Fifty-five constipated and 99 incontinent patients and healthy control subjects underwent manometry. Various parameters of the rectoanal inhibitory reflex were analyzed, and percentage sphincter relaxation was calculated at each volume at which rectoanal inhibitory reflex occurred. There was no difference in the volume of rectal distention required to elicit sensation (P = 0.626) or the rectoanal inhibitory reflex (P = 0.371) in the three groups. There was a significant correlation between the volume required to elicit the rectoanal inhibitory reflex and that at which sensation was first felt only in the incontinent (P = 0.0001) group. Significantly greater sphincter relaxation was seen at each volume (P = 0.001) in the incontinent as compared with the constipated patients. With progressive rectoanal inhibitory reflex, consistently progressive increases in internal anal sphincter relaxation were found only in the incontinent group. This consistent relationship was not seen in the constipated patients or in healthy control subjects. Assessment of various parameters of the rectoanal inhibitory reflex yielded important information regarding the continence mechanism. Altered responses of the internal anal sphincter in anorectal disorders plays a role in the associated physiologic impairment. This may have significant clinical implications with regard to sphincter-saving resections.

Anal achalasia after pull-through operations for Hirschsprung's disease -- preliminary experience with topical nitric oxide.

Following definitive pull-through for Hirschsprung's disease (HD), a minority of patients develop constipation, incontinence and enterocolitis. The cause for these symptoms in some of the patients is believed to be "internal sphincter achalasia" related to abnormal innervation of the sphincter, with an absent anorectal relaxation reflex. Transanal myectomy, posterior sagittal rectal myectomy, anal dilatation and even intrasphincter injection of botulinum toxin have been used to solve this problem. Nitric oxide (NO) has been identified as the chemical messenger of the intrinsic non-adrenergic, non-cholinergic pathway mediating relaxation of the normal internal anal sphincter when applied topically. To evaluate the effect of topical isosorbide dinitrate (DTN) applied to the anus and its role in the management of patients with HD after pull-through who have ongoing difficulties in stool evacuation. Four children, aged 2, 5, 7 and 13 years, who all underwent the Soave operation for Hirschsprung's disease, were assessed. Three patients had recurrent episodes of enterocolitis, and all had symptoms of difficulty in rectal/colonic evacuation. Conservative treatment of repeated anal dilatation under anaesthesia had failed to improve symptoms. A rectal myectomy and conversion of Soave to Duhamel procedure had been done in 2 without significant improvement in symptoms. In all patients, ano-rectal manometry was performed before and after application of DTN paste (1 mg/kg/day in two separate doses) which was continued for a minimum period of 3 weeks. Results. Marked symptom improvement was noted in all 4 children. On manometric assessment the median maximum pressure (pre-DTN application) was 165 mm Hg (range 96 - 250), the median sphincter length 2.7 cm (range 2.3 - 3.1) and the high-pressure zone (HPZ) median length 1.6 cm (range 1.2 - 2.1). After application of DTN paste, the maximum pressure dropped by a median of 88 mm Hg (range 46 - 90), total sphincter length shortened to a median of 2.1 cm and the HPZ by a median total length of 1.4 cm (range 0.01 - 0.9). In addition, vector volume was reduced by a median of 59 % (range 40.5 - 77). From these results, it is evident that DTN paste is not only an adjunct in the investigation, but can also be used as a temporary form of treatment of obstructive symptoms in Hirschsprung's disease patients.

Spontaneous internal anal sphincter relaxations and fecal incontinence

Spontaneous internal anal sphincter relaxations and fecal incontinence

Proctalgia fugax

Proctalgia fugax is a benign, self-limiting pain experienced in the perineum. It is common, but most sufferers do not seek medical advice. The aetiology is unclear, but a variation of irritable bowel syndrome, pelvic floor myalgia, and internal anal sphincter spasm have all been suggested. A careful history can elicit the characteristic history, and simple reassurance is often all that is necessary. For persistent symptoms, therapies that induce internal anal sphincter relaxation are of value.

The role of nitric oxide (NO) in the human internal anal sphincter.

Nitric oxide (NO) has recently been shown to be a neurotransmitter in nonadrenergic noncholinergic (NANC) inhibitory nerves in the human gut. To clarify the physiological significance of NO in the human internal anal sphincter (IAS), we investigated enteric nervous responses in normal IAS muscle strips above the dentate line, obtained from patients with rectal cancer. Normal IAS muscle strips above the dentate line, obtained from ten patients who underwent rectal amputation for low rectal cancers were used. The subjects consisted of eight men and two women, aged from 46-72 years (mean age, 54.2 years). A mechanographic technique was used to evaluate in-vitro IAS muscle responses to electrical field stimulation (EFS) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers, N(G)-nitro-L-arginine (L-NNA) and L-arginine. Excitatory nerves were mainly involved in the regulation of enteric nerve responses to EFS in the baseline condition of the study, and NANC inhibitory nerves acted on the normal IAS. L-NNA concentration-dependently inhibited the relaxation in response to EFS in the human IAS, and this inhibitory effect in the IAS was reversed by L-arginine. These findings suggest that NANC inhibitory nerves play important roles in regulating relaxation of the human IAS, and that NO plays an important role as a neurotransmitter in NANC inhibitory nerves of the human IAS.

Effect of continuous rectal distention on anal resting pressure.

Intermittent distention of the rectum induces internal anal sphincter relaxation, but whether continuous rectal distention might affect the resting pressure of the anal canal and the frequency of internal anal sphincter relaxations has not yet been investigated. The aim of this study was to record anal pressure under resting conditions and at two levels of continuous rectal distention. Anal pressure was recorded by means of water-perfused catheters under resting conditions and at two levels of rectal distention controlled by an electronic barostat in eight healthy subjects. Continuous rectal distention did not significantly change mean anal resting pressure, but it did significantly decrease the amplitude of ultraslow waves (from 29 +/- 9 mmHg under resting conditions to 23 +/- 6 and 21 +/- 3 mmHg during lesser and greater rectal distention; P = 0.017 and P = 0.012, respectively) and increase the frequency of internal anal sphincter relaxations (from 1.3 +/- 1.3/hour under resting conditions to 8.8 +/- 4.3/hour and 11.0 +/- 4.8/hour during lesser and greater distention; P = 0.012 in both comparisons). The resting pressure of the anal canal is maintained during continuous rectal distention. The decreased amplitude of ultraslow waves and increased frequency of the internal anal sphincter relaxations induced by rectal distention reveal a complex functional relationship between the rectum and the anal canal.

CGRP(2) receptor in the internal anal sphincter of the rat: implications for CGRP receptor classification.

The CGRP receptor mediating relaxation of the rat internal anal sphincter (IAS) has been characterized using CGRP analogues, homologues, the antagonist CGRP(8 - 37) and its analogues. In isolated IAS strips, the spontaneously developed tone was concentration-dependently relaxed by halpha CGRP, hbeta CGRP and rat beta CGRP (pEC(50) 8.1+/-0.2, 8.3+/-0.1 and 8.4+/-0.2, respectively; 100% maximum response). Vasoactive intestinal polypeptide (VIP) was around 7 fold more potent than halpha CGRP (pEC(50) 9.0+/-0.1; 100% maximum relaxation). [Cys(ACM(2.7))] halpha CGRP and salmon calcitonin were inactive (up to 10(-5) M). Halpha CGRP(8 - 37) (10(-5) M) antagonized responses to halpha CGRP (apparent pK(B) 5.7+/-0.3) and rat beta CGRP (apparent pK(B) 5.8+/-0.2), but not to VIP. Hbeta CGRP(8 - 37) (10(-5) M) was an antagonist against halpha CGRP (apparent pK(B) 6.1+/-0.1). Halpha CGRP(8 - 37) analogues (10(-5) M), with substitutions at the N-terminus by either glycine(8) or des-NH(2) valine(8) or proline(8), antagonized halpha CGRP responses with similar affinities (apparent pK(B) 5.8+/-0.1, 5.8+/-0.1 and 5.5+/-0.1, respectively). Peptidase inhibitors (amastatin, bestatin, captopril, phosphoramidon and thiorphan, 10(-6) M each) did not increase the agonist potency of either halpha CGRP or [Cys(ACM(2,7))] halpha CGRP, or the antagonist affinity of halpha CGRP(8 - 37) against halpha CGRP or rat beta CGRP. These data demonstrate for the first time a CGRP receptor in the rat IAS for which halpha CGRP (8 - 37) and its analogues have an affinity that is consistent with a CGRP(2) receptor. However, there is a marked species difference as the antagonist has a 100 fold lower affinity in the rat than in the same tissue of the opossum (Chakder & Rattan, 1991).

In vitro relaxation of rabbit and human internal anal sphincter by rutaecarpine, an alkaloid isolated from Evodia rutaecarpa

Rutaecarpine, a compound extracted from the Chinese medicinal herb Evodia rutaecarpa, has been shown to possess relaxing action on vascular smooth muscle from rat thoracic aorta. The internal anal sphincter is a specialized smooth muscle regulating important anorectal physiology. To investigate the effect and underlying mechanisms of rutaecarpine on internal anal sphincter, muscle strips from rabbit internal anal sphincter were used. The results showed that rutaecarpine (1 × 10 −10M to 1 × 10 −4M) produced a concentration-dependent muscular relaxation effect in our preparations, which were precontracted with acetylcholine. This muscular relaxation effect was not affected by treatment with L-N G-nitro-arginine methyl ester (a nitric oxide synthase inhibitor), methylene blue (a guanylate cyclase inhibitor), N-ethylmaleimide (an adenylate cyclase inhibitor), or by removal of the mucosa and submucosa tissue. Pretreatment with nifedipine (a calcium channel blocker) or extracellular Ca +2 removal by ethylenediaminetetraacetic acid (EDTA) greatly attenuated the relaxation effect, suggesting that calcium ion might be involved. In experiments using strips from human internal anal sphincter, an even more prominent relaxation effect was shown. It is thus concluded that rutaecarpine caused relaxation on internal anal sphincter from rabbits and human subjects. The relaxation action was not related to NO-cGMP pathway, instead calcium ion might play an important role and shed insight into clinical implications for those anorectal disorders with hyperactive anal tone.

Local somatothermal stimulation inhibits motility of the internal anal sphincter through nitrergic neural release of nitric oxide.

A somatoanal reflex had been demonstrated in our previous work. Because nitric oxide plays an important role in mediating relaxation of the internal anal sphincter, our purpose was to examine whether and how local somatothermal stimulation inhibits the function of the internal anal sphincter by stimulating nitric oxide release via nitrergic neurons and to elucidate the possible mechanism. The activity of the internal anal sphincter in anesthetized rabbits was measured by use of continuously perfused, open-tip manometric methods. Local somatothermal stimulation was achieved by applying an electroheating rod 1 cm away from the skin area at the right popliteal region. The responses were further manipulated by pre-treating the rabbits with agonists or antagonists linked to nitric oxide synthesis. The motility of the internal anal sphincter before and during local somatothermal stimulation was significantly different (tonic pressure (mean +/-standard error of the mean), 5.4 +/- 0.3 vs. 4.9 +/- 0.3 mmHg, P = 0.0195; phasic pressure, 3.9 +/- 0.6 vs. 2.9 +/- 0.4 mmHg, P = 0.0002; frequency distribution of the phasic contractions (peak-to-peak interval), 28.9 +/- 3.7 vs. 65.3 +/- 10.4 seconds, P = 0.0001). The response began at approximately one minute after local somatothermal stimulation when the skin temperature was 41 +/- 0.3 degrees C. No anal response was observed when local somatothermal stimulation was applied at the control area. The local somatothermal stimulation-induced internal anal sphincter relaxation was not inhibited by pretreatment with atropine, propranolol, or phentolamine (tonic pressure, 5.8 +/- 1 vs. 5.2 +/- 0.8 mmHg, P = 0.038; phasic pressure, 4.2 +/- 0.9 vs. 3.1 +/- 0.6 mmHg, P = 0.020; peak-to-peak interval, 27.2 +/- 4.3 vs. 52.9 +/- 14.5 seconds, P = 0.043) but was completely blocked by pretreatment with a nitric oxide synthesis inhibitor. The effect of the nitric oxide synthesis inhibitor could be reversed by pretreatment with L-arginine (tonic pressure, 6 +/- 0.7 vs. 5.6 +/- 0.7 mmHg, P = 0.047; phasic pressure, 4.7 +/- 0.7 vs. 3.9 +/- 0.5 mmHg, P = 0.048; peak-to-peak interval, 23.8 +/- 3 vs. 33 +/- 3.7 seconds, P = 0.048), but not by D-arginine. Local somatothermal stimulation inhibits internal anal sphincter motility through the activation of nonadrenergic noncholinergic neural release of nitric oxide. This procedure may represent a simplified approach for the treatment of anorectal diseases with hypofunction of the L-arginine/nitric oxide pathway. [Key words: Local somatothermal stimulation; Nitric oxide; Internal anal sphincter; Motility; Moxibustion] Jiang J-K, Chiu J-H, Lin J-K. Local somatothermal stimulation inhibits motility of the internal anal sphincter through nitrergic neural release of nitric oxide.

Nitrergic and purinergic mechanisms and their interactions for relaxation of the rat internal anal sphincter.

1. The NANC neuronal mechanisms for relaxations of the rat internal anal sphincter in response to electrical field stimulation (EFS) were studied in isolated preparations in the presence of atropine (1 microM), propranolol (3 microM) and phentolamine (3 microM). 2. EFS-induced relaxations were abolished by tetrodotoxin (1 microM) and reduced to 64% of control by the guanylate cyclase inhibitor ODQ (1 microM), but were not significantly reduced by the nitric oxide synthase inhibitor L-NAME (100 microM) or oxyhaemoglobin (10 microM). However, in the presence of tubocurarine (10 microM) or apamin (0.1 microM), L-NAME or oxyhaemoglobin greatly reduced or abolished EFS-induced relaxations. 3. The EFS-induced relaxations were mimicked by NO (10-100 microM) and by ATP (3-10 mM). The relaxations elicited by these agents were not affected by tetrodotoxin, L-NAME, tubocurarine or apamin. However, ATP-induced relaxations were reduced by the combination of L-NAME with tubocurarine or apamin. 4. Nicotine (10-100 microM) produced concentration-dependent relaxations that were abolished by tubocurarine (10 microM) or hexamethonium (200 microM). After desensitisation to nicotine (100 microM) and in its continued presence, the addition of L-NAME (100 microM) resulted in almost complete abolition of EFS-induced relaxations. 5. It is suggested that tubocurarine, hexamethonium and desensitisation to nicotine have an apamin-like action in the rat internal anal sphincter, the main effect being blockade of a purinergic component of the relaxant transmission process. 6. The findings suggest that both nitrergic and purinergic transmissions are involved in EFS-induced NANC relaxations of the rat internal anal sphincter, and there appears to be a complex interaction between these two pathways of transmission.

Treatment of chronic anal fissure with isosorbide dinitrate: long-term results and dose determination.

Anal fissure is a tear of the anoderm, which eventually can become an ulcer. Chronic anal fissure is perpetuated by contraction of the internal sphincter, believed to reduce perfusion. Nitric oxide is a neurotransmitter mediating vasodilation and internal anal sphincter relaxation. The aim of the present study was to evaluate both the effect and the effective dose regimen of isosorbide dinitrate, a nitric oxide donor, as a treatment for chronic anal fissure. Isosorbide dinitrate, Isoket spray (Schwarz-Pharma, Mannheim, Germany), was used to treat 41 patients with chronic anal fissure. Anal manometry was performed in all patients before they entered the study. The treatment program consisted of digital application of isosorbide dinitrate in a dose of 1.25 mg or 2.5 mg three times each day for four weeks. At the end of the trial, patients were followed up for an average time of 11 +/- 1 months. In 34 (83 percent) patients, the fissure healed within one month of treatment (mean, 3 +/- 0.1 weeks). The average time for symptoms to disappear was 6.5 +/- 0.7 days. In six (14.6 percent) patients the anal fissure did not heal even after four weeks of further treatment, and they underwent lateral sphincterotomy. Six patients relapsed during the follow-up period, but responded to another course of treatment. A dose of 2.5 mg of isosorbide dinitrate caused a greater reduction in maximum anal resting pressure than a dose of 1.25 mg. Topical isosorbide dinitrate is an effective and safe treatment for chronic anal fissure. In our experience the optimal dose regimen is 2.5 mg three times each day.

Involvement of pituitary adenylate cyclase-activating peptide in opossum internal anal sphincter relaxation

Despite its widespread distribution and significance in the gut, the role of pituitary adenylate cyclase-activating peptide (PACAP) in internal anal sphincter (IAS) relaxation has not been examined. This study examined the role of PACAP in nonadrenergic noncholinergic (NANC) nerve-mediated relaxation of IAS smooth muscle. Circular smooth muscle strips from the opossum IAS were prepared for measurement of isometric tension. The influence of PACAP and vasoactive intestinal peptide (VIP) antagonists and tachyphylaxis on the neurally mediated IAS relaxation was examined either separately or in combination. The release of these neuropeptides in response to NANC nerve stimulation before and after the nitric oxide (NO) synthase inhibitor Nomega-nitro-L-arginine and NO was also investigated. Both PACAP and VIP antagonists caused significant attenuation of IAS relaxation by NANC nerve stimulation. The combination of the antagonists, however, did not have an additive effect on IAS relaxation. VIP tachyphylaxis caused significant suppression of IAS relaxation by NANC nerve stimulation. PACAP and VIP were found to be released by NANC nerve stimulation and exogenous NO. The data suggest the involvement of PACAP in IAS relaxation primarily by the activation of PACAP1/VIP receptor and lack of its independent role in the relaxation. Furthermore, NO may regulate the presynaptic release of PACAP and VIP.

Corrigendum

Corrigendum

Evidences for a new colonic motor pattern: Not only propagating but also simultaneous high amplitude contractions are related to internal anal sphincter relaxation

Evidences for a new colonic motor pattern: Not only propagating but also simultaneous high amplitude contractions are related to internal anal sphincter relaxation

Constipation and Encopresis in Childhood

Constipation and Encopresis in Childhood

L-citrulline recycling in opossum internal anal sphincter relaxation by nonadrenergic, noncholinergic nerve stimulation

BACKGROUND & AIMS: L-citrulline formed stoichiometrically along with nitric oxide (1:1) from L-arginine may be enzymatically converted to L- arginine. The possibility of L-citrulline recycling in the maintenance of nitrergic neurotransmission in the opossum internal anal sphincter (IAS) smooth muscle strips was investigated. METHODS: Responses to nonadrenergic, noncholinergic (NANC) nerve stimulation by electrical field stimulation (EFS) (either short-train or continuous stimulation) on the basal IAS tension were recorded before and after the NO synthase inhibitor N(omega)-nitro-L-arginine (L-NNA), L-NNA plus L-citrulline, or L-arginine. During continuous EFS, when the basal IAS tone after the initial relaxation had recovered to almost pre-EFS levels, the effects of L-citrulline or L-arginine were examined before and after L- glutamine, which is a putative blocker of L-citrulline uptake. RESULTS: Inhibition of NANC nerve-mediated IAS relaxation by L-NNA was reversed by L-citrulline as well as L-arginine. L-Citrulline and L-arginine caused concentration-dependent relaxation of the IAS tone recovered during the prolonged EFS. L-Glutamine blocked the responses of L- citrulline but not of L-arginine. Furthermore, L-glutamine increased the speed of recovery of IAS tone during continuous EFS. CONCLUSIONS: L- citrulline recycling may be responsible for the maintenance of IAS relaxation during frequent short-train and prolonged NANC nerve stimulation. (Gastroenterology 1997 Apr;112(4):1250-9)

Neuronal mediators of inhibitory junction potentials and relaxation in the guinea-pig internal anal sphincter.

1. Inhibitory junction potentials (IJPs) and relaxations evoked in response to field stimulation (supramaximal voltage, 0.1 ms, single stimulus and 5 stimuli at 5-40 Hz) of non-adrenergic non-cholinergic (NANC) nerves with atropine and phentolamine (each 1 microM) were measured in the guinea-pig internal anal sphincter (gpIAS). The mean resting membrane potential was -44.2 +/- 0.2 mV (n = 1119 cells from 260 preparations). 2. NANC nerve stimulation evoked frequency-dependent IJPs (19.7 +/- 1.1 mV, n = 165, 33 tissues to a single stimulus) and relaxations. IJPs consisted of two tetrodotoxin (1 microM)-sensitive components: one was abolished by apamin (0.3 microM) and the P2-purinoceptor antagonist suramin (100 microM); the other, smaller in amplitude, was sensitive to inhibitors of nitric oxide synthase (NOS, e.g. L-NAME, 100 microM) and the nitric oxide (NO) scavenger oxyhaemoglobin (HbO, 10 microM). 3. ATP (1 mM), vasoactive intestinal polypeptide (VIP, 0.01-0.25 microM) and pituitary adenylate cyclase-activating peptide (PACAP(1-27), 0.84 microM) each hyperpolarized and relaxed the gpIAS; only ATP responses resembled the evoked IJPs in time course. 4. The guanylyl cyclase inhibitor LY83583 (10 microM) abolished apamin-insensitive IJPs and relaxations. The cGMP phosphodiesterase inhibitor M&B 22948 (30 microM) and 8-Br-cGMP (100 microM) each hyperpolarized the gpIAS. 5. Two components comprise the IJP and relaxation evoked in response to NANC nerve stimulation in the gpIAS. One, sensitive to apamin, resembles the response to ATP and is modulated by purinoceptor antagonists; the other, apamin and suramin insensitive, is inhibited by NO antagonists.

Gradient of pressure and time between proximal anal canal and high-pressure zone during internal anal sphincter relaxation

The normal response to rectal distention is a relaxation of the proximal anal canal (PAC). We hypothesized that this mechanism would require a gradient of pressure and time to preserve continence. Sixteen volunteers (10 male), mean age, 41.5 (range, 24-60) years, were studied using an eight port axial catheter with a compliant balloon at its tip. Relaxation was induced by a small volume of rectal distention (15-30 ml of air) and was recorded until recovery of resting anal pressure (RAP). Duration of relaxation was measured until recovery of RAP. Amplitude of relaxation was determined between RAP before rectal distention (RAP-BR) and pressure at the point of maximum relaxation (RAP-PMR). Gradient of pressure was determined by comparing RAP-PMR in the high-pressure zone (HPZ) and PAC. Contraction in the distal anal canal was interpreted as external anal sphincter contraction (EASC) and was compared with RAP-PMR in the HPZ. Relaxation was significantly greater in PAC than in HPZ (50 vs. 36 percent; P = 0.001). RAP-PMR was significantly higher in HPZ than in PAC (30.7 vs. 12.6 mmHg; P = 0.001). EASC was observed in six patients and did not show significant difference with RAP-PMR in HPZ (39.7 vs. 36.3 mmHg; not significant). Relaxation began at the same time in all levels but lasted significantly longer in PAC compared with HPZ (13.5 vs. 9.4 sec; P = 0.003). Anal relaxation induced by small volume rectal distention involves a gradient in the pressure and time of relaxation between PAC and the HPZ.

Hyperglycemia alters perception of rectal distention and blunts the rectoanal inhibitory reflex in healthy volunteers

Background/Aims: Acute hyperglycemia has been shown to alter gastrointestinal motility. The effects of hyperglycemia on rectal afferent neural and anal sphincter function were studied. Methods: Perception of rectal balloon distention, pressure-volume relationships, volumes necessary to induce reflex internal anal sphincter relaxation, resting anal sphincter pressure, and maximal anal sphincter squeeze pressure were measured under basal, hyperglycemic clamp, and euglycemic, hyperinsulinemic clamp conditions in 9 healthy volunteers. Results: Hyperglycemic clamping (258 ± 14 mg/dL) significantly blunted threshold perception and the urge to defecate in response to rectal distention without altering perception of maximally tolerated distention. In contrast, euglycemic, hyperinsulinemic clamping had no effect on perception of rectal distention. Rectal pressure-volume relationships after hyperglycemic clamping were unchanged compared with basal conditions. Hyperglycemic clamping caused a significant increase in the distention necessary to induce the rectoanal inhibitory reflex. This effect was not observed under euglycemic, hyperinsulinemic clamp conditions. Hyperglycemia did not significantly affect resting internal anal sphincter pressure or maximal external anal sphincter squeeze pressure. Conclusions: Acute hyperglycemia but not secondary hyperinsulinemia reduces sensation of rectal distention and blunts the onset of the rectoanal inhibitory reflex, suggesting effects both on visceral afferents projecting to the cortex and intrinsic afferents mediating local reflex activity.

Hereditary proctalgia fugax and constipation: report of a second family.

A second family with hereditary proctalgia fugax and internal anal sphincter hypertrophy associated with constipation is described. Anorectal ultrasonography, manometry, and sensory tests were conducted in two symptomatic and one asymptomatic subjects within the same family and further clinical information was obtained from other family members. The inheritance would correspond to an autosomal dominant condition with incomplete penetration, presenting after the second decade of life. Physiological studies showed deep, ultraslow waves and an absence of internal anal sphincter relaxation on rectal distension in the two most severely affected family members, suggesting the possibility of a neuropathic origin. Both of these patients had an abnormally high blood pressure. After treatment with a sustained release formulation of the calcium antagonist, nifedipine, their blood pressure returned to normal, anal tone was reduced, and the frequency and intensity of anal pain was suppressed. These together improved the quality of the patients' sleep, which had previously been very troubled because of night time attacks of anal pain.