Comparing right colon adenoma detection rate during water exchange and air insufflation: a double-blind randomized controlled trial.

BACKGROUND: Randomized controlled trials (RCTs) have reported that water exchange (WE) produced the highest adenoma detection rate (ADR) but did not evaluate right colon adenoma detection rate (rADR) as a primary outcome and only one of the trials employed blinded colonoscopists. The aim of our study was to determine whether, compared with air insufflation, WE significantly increases rADR and right colon serrated lesion detection rate (rSLDR) and decreases adenoma miss rate (rAMR). METHODS: This prospective, double-blind RCT was conducted at a regional hospital in Taiwan between December 2015 and February 2020. Standard WE and air insufflation were performed. After cecal intubation, the second blinded endoscopist examined the right colon and obtained rADR (primary outcome) and rSLDR. Then, the primary colonoscopist reinserted the scope to the cecum with WE in both groups and performed a tandem examination of the right colon to obtain rAMR. RESULTS: There were 284 patients (50.9% male, mean age 58.9 ± 9.4 years) who were randomized to WE (n = 144) or air insufflation (n = 140). The baseline characteristics were similar. The rADR (34.7% vs. 22.3%, p = 0.025), Boston Bowel Preparation Scale scores (mean, 2.6 ± 0.6vs. 2.2 ± 0.6, p < 0.001), rSLDR (18.1% vs. 7.1%, p = 0.007), and rAMR (31.5% vs. 45.2%, p = 0.038) were significantly different between WE and air insufflation. CONCLUSIONS: The current study demonstrated a significantly higher rADR and rSLDR with the WE method performed by blinded colonoscopists. The impact of the significant findings in this report on the occurrence of interval cancers deserves to be studied.

Underwater polypectomy without submucosal injection for colorectal lesions ≤ 20 mm in size-a multicenter retrospective observational study.

BACKGROUND: Underwater polypectomy (UWP) of large (≥ 20 mm) colorectal lesions is well described, but reports of UWP for lesions ≤ 20 mm in size, which account for > 95% of polyps encountered in routine clinical practice, are limited. We assessed the feasibility of UWP in routine practice across various sites for colorectal lesions ≤ 20 mm in size. METHODS: A multicenter retrospective study was performed on pooled data from nine colonoscopists at 3 U.S., 1 Taiwanese and 2 Italian sites. Outcomes related to UWP on lesions ≤ 20 mm in size were analyzed. RESULTS: In 117 patients, UWP netted 169 lesions. Polypectomy by hot (HSP, 54%) or cold (CSP, 41%) snare, and cold forceps (CFP, 5%) were performed successfully without endoscopic evidence of residual neoplasia or immediate clinically significant adverse events. The majority (74.6%) were tubular adenomas; 60.9% were from the proximal colon. Histopathologic margins were positive in 4 and unavailable in 26 CSP and 24 HSP specimens. The remainder had negative resection margins on pathologic reports. CONCLUSION: UWP for colorectal lesions ≤ 20 mm in routine practice across multiple sites confirms the feasibility and acceptability of this technique. Improvement of resection outcomes by UWP in routine practice deserves further evaluation in a randomized controlled trial.

The water method significantly enhances patient-centered outcomes in sedated and unsedated colonoscopy.

Failure of cecal intubation when using air insufflation during scheduled unsedated colonoscopy in veterans prompted a literature search for a less uncomfortable approach. Water-related maneuvers as "adjuncts" to air insufflation were identified as effective in minimizing discomfort, although medication requirement was not reduced and willingness to repeat unsedated colonoscopy was not addressed. These adjunct maneuvers were combined with turning the air pump off to avoid colon elongation during insertion. Warm water infusion in lieu of air insufflation was evaluated in observational studies. Subsequent refinements evolved into the water method - a combination of air exclusion by aspiration of residual air to minimize angulations at flexures and a dynamic process of water exchange to remove feces in order to clear the view and aid insertion. In subsequent randomized controlled trials, the water method significantly reduced medication requirement, increased the proportion of patients in whom complete unsedated colonoscopy could be achieved, reduced patient recovery time burdens (sedation on demand), decreased abdominal discomfort during and after colonoscopy, enhanced cecal intubation, and increased willingness to repeat the procedure (scheduled unsedated). Supervised education of trainees and self-learning by an experienced colonoscopist were feasible. Lessons learned in developing the water method for optimizing patient-centered outcomes are presented. These proof-of-principle observations merit further research assessment in diverse settings.

Water immersion versus standard colonoscopy insertion technique: randomized trial shows promise for minimal sedation.

BACKGROUND AND STUDY AIMS: Water immersion is an alternative colonoscopy technique that may reduce discomfort and facilitate insertion of the instrument. This was a prospective study to compare the success of colonoscopy with minimal sedation using water immersion and conventional air insufflation. PATIENTS AND METHODS: A total of 229 patients were randomized to either water immersion or the standard air insertion technique. The primary outcome was success of minimal sedation colonoscopy, which was defined as reaching the cecum without additional sedation, exchange of the adult colonoscope or hands-on assistance for trainees. Patient comfort and satisfaction were also assessed. RESULTS: Successful minimal-sedation colonoscopy was achieved in 51 % of the water immersion group compared with 28 % in the standard air group (OR, 2.66; 95 % CI 1.48 - 4.79; P = 0.0004). Attending physicians had 79 % success with water immersion compared with 47 % with air insufflation (OR, 4.19; 95 % CI 1.5 - 12.17; P = 0.002), whereas trainees had 34 % success with water compared with 16 % using air (OR, 2.75; 95 % CI 1.15 - 6.86; P = 0.01). Using the water method, endoscopists intubated the cecum faster and this was particularly notable for trainees (13.0 +/- 7.5 minutes with water vs. 20.5 +/- 13.9 minutes with air; P = 0.0001). Total procedure time was significantly shorter with water for both experienced and trainee endoscopists ( P < 0.05). Patients reported less intraprocedural pain with water compared with air (4.1 +/- 2.7 vs. 5.3 +/- 2.7; P = 0.001), with a similar level of satisfaction. There was no difference in the neoplasm detection rates between the groups. CONCLUSION: Colonoscopy insertion using water immersion increases the success rate of minimal sedation colonoscopy. Use of the technique leads to a decrease in discomfort, time to reach the cecum, and the amount of sedative and analgesic used, without compromising patient satisfaction.

A prospective RCT comparing combined chromoendoscopy with water exchange (CWE) vs water exchange (WE) vs air insufflation (AI) in adenoma detection in screening colonoscopy.

Background: A low adenoma detection rate (ADR) increases risks of interval cancers (ICs). Proximal colon flat polyps, e.g. serrated lesions (SLs), are difficult to find. Missed proximal colon flat lesions likely contribute to IC. Aims: We compared chromoendoscopy with water exchange (CWE), water exchange (WE) and air insufflation (AI) in detecting adenomas in screening colonoscopy. Methods: After split-dose preparation, 480 veterans were randomized to AI, WE and CWE. Results: Primary outcome of proximal ADR (55.6% vs 53.4% vs 52.2%, respectively) were similar in all groups. Adenoma per colonoscopy (APC) and adenoma per positive colonoscopy (APPC) were comparable. Detection rate of proximal colon SLs was significantly higher for CWE and WE than AI (26.3%, 23.6% and 11.3%, respectively, p = 0.002). Limitations: single operator; SLs only surrogate markers of but not IC. Conclusions: When an endoscopist achieves high-quality AI examinations with overall ADR twice (61.6%) the recommended standard (30%), use of WE and CWE does not produce further improvement in proximal or overall ADR. Comparable APC and APPC confirm equivalent withdrawal inspection techniques. WE alone is sufficient to significantly improve detection of proximal SLs. The impact of increased detection of proximal SLs by WE on prevention of IC deserves to be studied. This study is registered at ClinicalTrial.gov (NCT#01607255).

Comparison of accessory performance using a novel ERCP mechanical simulator.

BACKGROUND AND STUDY AIMS: There is a paucity of in vitro methods for evaluating ERCP accessories. We hypothesize that the time taken to perform a simulated single stent or multiple stents placement is different for stenting systems with or without the capability of intraductal ductal release (IDR) of the guide wire. PATIENTS AND METHODS: We conducted an un-blinded in vitro comparison of ERCP accessories using a mechanical simulator during hands-on ERCP practice workshops. A total of 21 U.S. participants and 20 Chinese participants with various level of ERCP experience took part in the different practice workshops. Accessories with and without the capability of intraductal release of guide wire were compared. Total time required for completing a simulated stenting procedure with single or multiple stents and the respective simulated fluoroscopy time were recorded. RESULTS: There was no significant difference in the time taken for placement of a single stent using either stenting systems. Stenting system capable of intraductal release of the guide wire required significantly shorter time to complete placement of three stents. CONCLUSIONS: Using time required to complete a specific task, i. e. biliary stenting, the mechanical simulator permits the performance of different accessories by the same group of operators to be evaluated objectively.

Options for screening colonoscopy without sedation: a pilot study in United States veterans.

BACKGROUND: The direct and indirect costs of sedation limit access to screening colonoscopy amongst United States veterans. AIM: To determine if offering the option of sedation on-demand reduces the need for sedation. Design A retrospective review of prospectively collected performance improvement data in an open access screening colonoscopy programme. SETTING: Performance improvement programme to minimize the burden of sedation at a single VA Medical Center. Subjects 44 consecutive veterans who accepted the option of sedation on-demand. They could choose to have premedications before the start of colonoscopy, or to begin colonoscopy without premedications and receive the medications upon their request during the examination. METHOD: Two experienced endoscopists assisted by experienced nurse assistants performed all of the examinations. Insertion of the colonoscope was aided by infusion of warm water through the colonoscope without air insufflation. Medications were administered at the veterans' request. RESULTS: Offering the option of sedation on-demand to 44 consecutive veterans permitted 52% (N = 23) of the veterans to complete screening colonoscopy without any sedation. CONCLUSIONS: This novel approach of sedation on-demand and water infusion for screening colonoscopy deserves to be further evaluated in a randomized-controlled study amongst patients undergoing colorectal cancer screening.

Papillotomy Performance Scoring Scale--a pilot validation study focused on the cut axis.

BACKGROUND: No published Papillotomy Performance Scoring Scale exists. AIMS: To develop such a scale and to apply it to stratify the quality of performance of recorded papillotomies. METHODS: Expert biliary endoscopists were polled regarding their opinion of a 'perfect' biliary papillotomy and experience with complications in relation to the cut axis. Based on these responses a scoring scale encompassing two components - wire alignment and cut orientation, was proposed. This scoring scale was presented to experienced and trainee endoscopists, who scored recording of five biliary papillotomies. The mean final combined score was used for stratification. RESULTS: The experts' opinion of a 'perfect' biliary papillotomy is one cut along the axis of the distal bile duct and papilla. Their reported experience with complications occurring outside of the perfect axis validated their consensus. Application of the scoring scale stratified recorded papillotomies based on the mean final combined scores. CONCLUSIONS: These pilot data support the hypothesis that a scoring scale focused on the cut axis can be constructed based on expert opinion, experience and consensus. The possibility of stratification of mean final combined scores that are significantly different validates application of the scoring scale for assessment of papillotomy performance.

Extended flexible sigmoidoscopy performed by colonoscopists for colorectal cancer screening: a pilot study.

BACKGROUND: Caecal intubation can be achieved by extended flexible sigmoidoscopy in 32% of patients. AIM: To assess the feasibility of extended flexible sigmoidoscopy performed by colonoscopists for colorectal cancer screening. METHODS: We enrolled 41 patients referred for screening flexible sigmoidoscopy. After purging, examination was performed with a colonoscope. All patients completed sigmoidoscopy (success in meeting referral goal); 93% and 71% had examination to the transverse or ascending colon, and caecum, respectively. Overall yield and right-sided polyps was 56% and 27%, respectively. Caecal intubation and complete examination with polypectomy took 6.0 +/- 2.5 and 18.3 +/- 5.1 min, respectively; with no complications. Twelve patients requested colonoscope withdrawal because of discomfort. Although 46% reported moderate to severe discomfort, 39% and 36%, respectively, were definitely or probably willing to repeat flexible sigmoidoscopy. RESULTS: Unsedated colonoscopy introduced as extended flexible sigmoidoscopy emphasizes the benefits of added yield rather than the negative image of withholding of discomfort relief. The patient can choose to accept the equivalent of an unsedated colonoscopy or reject the option based on perceived discomfort during extended flexible sigmoidoscopy performed by the colonoscopist. CONCLUSION: Extended flexible sigmoidoscopy is a feasible option in carefully selected patients, fully prepared and by an experienced colonoscopist.

Indomethacin potentiates endotoxin-induced blood flow reduction and histological injury in rat gastric mucosa.

1. The effect of the intravenous administration of lipopolysaccharide from Salmonella typhosa endotoxin on arterial blood pressure (BP), gastric mucosal blood flow (GMBF) and gastric damage was studied in anaesthetized rats. The effect of the inhibition of endogenous prostaglandin generation by indomethacin on these parameters was also investigated in this model of endotoxin shock. 2. A similar and dose-dependent percentage of reduction in BP and GMBF was observed 5 min after a bolus injection of 20 or 30 mg kg-1 endotoxin. A transient recovery in GMBF at 15 min was observed followed by a second fall at 30 min, at a time when BP was slowly increasing. 3. Pretreatment with indomethacin (5 mg kg-1, s.c.) one hour before the administration of 30 mg kg-1 endotoxin, significantly augmented the reduction in GMBF without affecting the reduction in BP. 4. The gastric damage, assessed histologically, was similar and confined to the superficial mucosa 30 min after the administration of 20 or 30 mg kg-1 endotoxin. The histologically-assessed damage was significantly greater in indomethacin pretreated rats injected with 30 mg kg-1 endotoxin. 5. These findings suggest that endogenous prostaglandin generation plays a protective role in endotoxin-induced gastric mucosal microcirculatory disturbances and mucosal damage.

Effect of acid on duodenal blood flow and mucus secretion measured by reflectance spectrophotometry: a prospective, randomized-controlled study.

BACKGROUND: In animals, hydrochloric acid increases blood flow and mucus secretion in the duodenal mucosa. A significant correlation between index of haemoglobin oxygen saturation and mucosal blood flow, and between change in index of haemoglobin concentration and mucus thickness, respectively, has been demonstrated by reflectance spectrophotometry. AIM: To examine the effect of topical hydrochloric acid upon mucosal blood flow and mucus secretion in the human duodenum. METHODS: This prospective study of 120 patients undergoing routine upper endoscopy, examined the effect of topical 0.1 n hydrochloric acid or 0.9% saline on the duodenal bulb in a randomized, double-blind fashion. Duodenal mucosal index of haemoglobin oxygen saturation and index of haemoglobin concentration were measured by endoscopic reflectance spectrophotometry before and after hydrochloric acid or saline. RESULTS: Baseline index of haemoglobin oxygen saturation, calculated blood flow and index of haemoglobin concentration measurements were comparable between hydrochloric acid (n = 60) and saline (n = 60) treated groups. A history of current use of non-steroidal anti-inflammatory drug was associated with a significantly lower baseline index of haemoglobin oxygen saturation and calculated blood flow. Hydrochloric acid resulted in a significant increase in index of haemoglobin oxygen saturation and calculated blood flow, but a decrease in index of haemoglobin concentration, reflecting an increase in mucus thickness compared with saline. CONCLUSIONS: Our observations in humans confirm data in animal studies that topical exposure to hydrochloric acid induces an increase in duodenal mucosal blood flow and mucus secretion. Post hoc analysis of the data also revealed that attenuation of basal duodenal mucosal blood flow is associated with a history of current non-steroidal anti-inflammatory drug use. Endoscopic reflectance spectrophotometry appears to be adequate to assess factors that influence duodenal defence mechanisms of blood flow and mucus secretion in humans.

Primary afferent nerves mediate in part beta-adrenoceptor stimulation-induced mesenteric hyperemia in rats.

We tested the hypothesis that in the rat duodenum and intestine the mesenteric hyperemia due to beta-adrenoceptor stimulation is mediated by capsaicin-sensitive afferent nerves. Superior mesenteric artery blood flow was measured by pulsed Doppler flowmetry in the anesthetized rat. Functional ablation of afferent nerves was accomplished by subcutaneous 125 mg/kg capsaicin pretreatment 10 to 14 days before blood flow studies. Blockade of capsaicin-sensitive cation-selective ion channels of the duodenal and intestinal mucosal afferent nerves was achieved by intraduodenal 0.1% ruthenium red given 15 min prior to the intraduodenal administration of 5 mg/kg isoproterenol. Functional ablation of the afferent nerves and blockade of the capsaicin-sensitive cation-selective ion channels alone or in combination resulted in a significant reduction of mesenteric hyperemia induced by intraduodenal isoproterenol. These data support the hypothesis that beta-adrenoceptor stimulation by intraduodenal isoproterenol induces mesenteric hyperemia in part through afferent nerves in the rat duodenal and intestinal mucosa. The results suggest for the first time a link between beta-adrenoceptor function and peripheral capsaicin-sensitive afferent nerve-mediated mechanism in the rat gut.

Functional evidence linking potassium channels and afferent nerve-mediated mucosal protection in rat stomach.

Adenosine triphosphate-dependent potassium (K+ATP) channels in several types of vascular smooth muscles mediate the vasodilation induced by calcitonin gene-related peptide (CGRP). Upon stimulation, primary afferent nerve terminals in the gastric mucosa release CGRP which mediates a protective hyperemia. We tested the hypothesis that a potassium channel blocker aggravates gastric mucosal injury by impairing afferent nerve-mediated hyperemia in the gastric mucosa. Rats were treated with K+ATP channel blocker, glybenclamide (20 mg/kg intravenously). Intragastric added ethanol (0.15 N HCl, 15% ethanol) and intragastric capsaicin (160 microM) were also administered. Glybenclamide aggravated the acidified ethanol-induced mucosal injury, and attenuated the mucosal hyperemia (hydrogen gas clearance) induced by intragastric acidified ethanol and intragastric capsaicin. These findings suggest for the first time that K+ATP channels modulate primary afferent nerve-mediated mucosal defense mechanisms in the gastric mucosa.

Mechanism of acid-induced mesenteric hyperemia in rats.

The mesenteric hyperemia induced by intraduodenal application of hydrochloric acid (HCl) is mediated in part by capsaicin-sensitive afferent nerves. Antagonist of capsaicin-sensitive receptors (capsazepine) and blocker of capsaicin-sensitive cation channels (ruthenium red) have been described. We employed these tools to dissect the mechanism of regulation of mesenteric hyperemia induced by intraduodenal administration of HCl. Subcutaneous 100 micromol/kg capsazepine or intraduodenal 0.1% ruthenium red was administered to pentobarbital anesthetized rats. Then, 2.5 ml/kg of 640 microM capsaicin or 0.1 N HCl was administered intraduodenally. The mesenteric hyperemic responses were recorded. The results demonstrated that in a dose that decreased the mesenteric hyperemia induced by intraduodenal capsaicin, capsazepine failed to attenuate the mesenteric vasodilatory effect of intraduodenal HCl. Ruthenium red significantly attenuated the mesenteric hyperemia after intraduodenal capsaicin and HCl. These in vivo data provide the first functional evidence for the existence of capsazepine-sensitive capsaicin receptors and cation channel complexes in the rat duodenal and intestinal mucosa. The capsaicin- and HCl-sensitive receptors are unlikely to be functionally identical in these locations. The ruthenium red-sensitive cation channels appear to mediate the capsaicin- and HCl-induced mesenteric hyperemia.

Epidermal growth factor increases basal mucosal blood flow in the rat colon, a prostaglandin dependent effect.

OBJECTIVE/BACKGROUND: Non-mitogenic biological activity such as modulation of mucosal blood flow is suspected to convey the protective effects of epidermal growth factor (EGF) in vivo. The aims of our present study were to determine the effects of EGF on colonic mucosal blood flow and injury induced hyperaemia in rats. DESIGN/METHODS: Rats were pretreated with i.p. injections of vehicle, EGF, or indomethacin and EGF prior to mucosal injury. Basal mucosal blood flow and injury induced hyperaemia at the border of the damaged mucosa was determined by using reflectance spectrophotometry. RESULTS: EGF significantly increased basal mucosal blood flow but did not further enhance injury induced hyperaemia. The EGF induced increase in basal mucosal blood flow was completely abolished by indomethacin pretreatment. CONCLUSIONS: EGF induces an increase of basal mucosal blood flow through induction of prostaglandin synthesis. We hypothesize that the increase in mucosal blood flow contributes to the ability of EGF to protect the colonic mucosa against injury.

Comparison of blood flow measurements by hydrogen gas clearance and laser Doppler flowmetry in the rat duodenum.

This report examines the relationship between hydrogen gas clearance and laser Doppler flowmetry measurements in the duodenum of fasted, anesthetized rats under conditions of 1) reduced perfusion due to graded levels of hemorrhagic hypotension or 2) hyperemia due to perfusion with step doses of acid. There was a significant correlation between hydrogen gas clearance and laser Doppler flowmetry measurements (r = 0.73, p less than 0.01; n = 32 data points in 16 rats). The change in laser Doppler flowmetry values from the period immediately before to the period during the 3 min of acid perfusion was significantly correlated with the dose of acid used (r = 0.51, p less than 0.01; n = 27 rats). The changes in hydrogen gas clearance and laser Doppler flowmetry values from the 30-min period before to the 30-min period after acid perfusion were not correlated with the dose of acid used (r = 0.30 and 0.33, respectively). We conclude that in the rat duodenum 1) the significant linear correlation between hydrogen gas clearance and laser Doppler flowmetry when blood flow is reduced suggests that the countercurrent exchange mechanism is unlikely to modulate significantly hydrogen gas clearance measurements, and 2) the dose-related acid-induced duodenal hyperemia is transient rather than persistent when the rat duodenum is exposed to hydrochloric acid (0.03 to 0.1 N) for 3 min.

Role of capsaicin-sensitive afferent nerves in mucosal injury and injury-induced hyperemia in rat colon.

Exposure of the colonic mucosa to 10% acetic acid results in ischemia and damage of the exposed mucosa and hyperemia in the adjacent unexposed and undamaged mucosa. We hypothesize that this hyperemia is mediated in part by capsaicin-sensitive afferent nerves, and absence of the hyperemia is associated with aggravation of damage in the exposed mucosa. In urethan-anesthetized rats, with the reflectance spectrophotometry probe in contact with the colonic mucosa, index of mucosal oxygen saturation (ISO2) was monitored before and for 5 min after 10% acetic acid was applied to the mucosa surrounding the measuring probe. Histological examination confirmed that the mucosa in contact with the measuring probe was undamaged, but the mucosa exposed to the 10% acetic acid was damaged. In the mucosa in contact with the reflectance spectrophotometry probe, a significant increase in ISO2 was observed in vehicle-pretreated rats, whereas a partial but significant reduction of such hyperemia was observed in capsaicin-pretreated rats. In the mucosa exposed to the 10% acetic acid, the depth of the mucosal lesion, but not the drop in ISO2, was significantly greater in the capsaicin-pretreated rats. The findings are consistent with the hypothesis that the colonic mucosal hyperemia in the undamaged mucosa adjacent to the mucosa damaged by the 10% acetic acid is mediated partially by capsaicin-sensitive afferent nerves. Attenuation of such hyperemia by capsaicin-pretreatment is associated with deeper mucosal damage, suggesting that the capsaicin-sensitive afferent nerves also contribute toward colonic mucosal protection against 10% acetic acid-induced injury in the exposed mucosa.

Modulation of autoregulatory escape by capsaicin-sensitive afferent nerves in rat stomach.

Visceral C fibers are stimulated by ischemia and hypoxia, which can be produced by intense vasoconstriction. Epinephrine applied to the gastric submucosa produces a marked vasoconstriction followed by autoregulatory escape. We hypothesize that the autoregulatory escape from epinephrine-induced vasoconstriction in the rat stomach is mediated partly by capsaicin-sensitive C fibers. Functional ablation of these afferent fibers by high-dose systemic capsaicin pretreatment will significantly reduce the magnitude of the autoregulatory escape. Rats received capsaicin (125 mg/kg sc) 10 days before blood flow studies to produce functional impairment of the capsaicin-sensitive afferent nerves. Control rats received vehicle. Under urethan anesthesia, a small area (2 mm diam) of the serosa from the anterior gastric wall was removed to expose the submucosa. The tip of a side-viewing laser-Doppler flow probe was placed inside the stomach directly beneath the exposed submucosa. At 20-min intervals, 20 microliters of buffer, 5 x 10(-4) M epinephrine, 1.6 x 10(-4) M capsaicin, or 3.3 x 10(-2) M histamine was applied topically to the exposed submucosa, with saline washes between applications at 10 min after each application. Blood pressure and laser-Doppler flow signals were monitored continuously. The escape index during the period of epinephrine application was significantly lower in the capsaicin-pretreated rats (0.239 +/- 0.046) than in the vehicle-pretreated rats (0.474 +/- 0.079). Functional ablation of the capsaicin-sensitive afferent fibers was confirmed by a significant blockade of the vasodilatation induced by topical capsaicin. Histamine-induced vasodilatation was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)