PubMed Health⌕ Search

Biomedical subjects

Pankaj J Pasricha

Publications and source records attributed to Pankaj J Pasricha.

At least 19 recordsLinked to original sources

The role of endoscopic ultrasound and endoscopic ultrasound-guided fine-needle aspiration in distinguishing pancreatic cystic lesions.

Distinguishing mucinous from nonmucinous cystic lesions of the pancreas often constitutes a diagnostic dilemma. The clinical management differs between such lesions; therefore it is important to make an accurate preoperative diagnosis. Various centers have reported conflicting results regarding their ability to detect mucin-producing neoplastic cells and appropriately reach a diagnosis based on endoscopic ultrasound (EUS) guided FNA. The aim of this study is to assess the ability of EUS-FNA cytology to diagnose and differentiate mucinous from nonmucinous pancreatic cystic lesions. We reviewed records of patients who underwent EUS of pancreatic cystic lesions. If FNA was performed and mucinous neoplasm was suspected, aspirate was evaluated for cytomorphology and presence of mucin. FNA results were compared to final histologic diagnosis if surgery was performed. Cytologic diagnosis was provided for 28/30 (93%). By comparing EUS-FNA diagnoses with final surgical pathology, FNA accurately diagnosed in 10/11 cases with sensitivity and specificity for detection of malignancy of 100 and 89, respectively, while the accuracy for identification of mucinous cystic neoplasms was 100%. Our results indicate that in the appropriate clinical and imaging setting, EUS-FNA cytology with analysis for mucin production by tumor cells is an important test in distinguishing pancreatic cystic lesions and guiding further management.

Adult↗

Endoscopic therapy for GERD: is the evidence for efficacy any stronger?

Gastroesophageal reflux disease (GERD) is a common chronic medical disorder that has a significant impact on quality of life and afflicts millions of people worldwide. Therapy with either daily medications or surgical fundoplication, though highly effective for the majority of patients, is not without long-term shortcomings. The development of endoscopic antireflux therapies has been fueled by the hope of providing safe, effective, long-term symptomatic relief. Although several studies have been published, they are limited by small sample size, lack of adequate controls, and a highly selective patient population. However, it is clear that many, if not most, patients will continue to be on acid-suppressive therapy despite these procedures. Also, reports of postmarketing adverse effects emphasize the need for further scrutiny of the safety of these devices. This review will summarize the available evidence and provide tentative conclusions about the current and evolving role of endoscopic antireflux therapy.

Journal Article↗

The endoscopic transilluminator: an endoscopic device for identification of the proximal jejunum for transgastric endoscopic gastrojejunostomy.

BACKGROUND: Localization of the proximal jejunum is important for creation of gastrojejunal anastomosis to palliate gastric outlet obstruction or for treatment of obesity with gastric bypass. OBJECTIVE: To facilitate identification of the proximal jejunum during transgastric endoscopic gastrojejunostomy with the use of an endoscopic transilluminator (ET). DESIGN AND SETTING: Acute experiments in a live porcine model. INTERVENTIONS: The ET is a 3500-mm long, 6F radio-opaque tube with a fiberoptic core that lights up at its distal end. When situated in the intestinal lumen, it transilluminates the bowel wall. With the animal under general anesthesia with endotracheal intubation, a colonoscope was advanced to the proximal jejunum. A plastic tube (3500-mm long, 3.5 mm in diameter) was passed through the biopsy channel and placed into the small bowel. The colonoscope was withdrawn, leaving the tube in place. The ET was introduced into the jejunum through the tube. A gastric wall incision was made and the endoscope was advanced to the peritoneal cavity. The transilluminated loop of the proximal jejunum was identified and gastrojejunal anastomosis was made by use of a previously reported endoscopic technique. MAIN OUTCOME MEASUREMENTS: Identification of the proximal jejunum. RESULTS: Eleven pigs (average weight 55 kg) had ET placement. In all of the pigs, placement of the ET was performed easily to the proximal small bowel, and the proximal jejunum was successfully localized by either direct visualization of the transilluminated loop only or with the aid of fluoroscopy. The tip of the ET was usually located about 50 to 70 cm distal to the ligament of Treitz. There were no complications related to the use of ET. LIMITATIONS: The device has not yet been evaluated in humans. CONCLUSIONS: The ET is a safe instrument and can be used to identify the proximal jejunum to facilitate endoscopic gastrojejunostomy.

Animals↗

Pilot study of the porcine uterine horn as an in vivo appendicitis model for development of endoscopic transgastric appendectomy.

BACKGROUND: Iatrogenic inflammation of the porcine uterine horn may serve as an in vivo appendicitis model for the development of endoscopic transgastric appendectomy. OBJECTIVE: Five female pigs. STUDY DESIGN: Animal study. SETTINGS: General anesthesia. MAIN OUTCOME MEASUREMENTS: Anatomical appearance and technical feasibility. INTERVENTIONS: Three pigs were used to identify an injectable material that would inflame the uterine horn, and 2 pigs were used for a pilot appendectomy. Three types of materials were individually injected into the bilateral uterine horns, and the ideal material to inflame the uterine horn was injected into the right uterine horn for the last 2 pigs. After 24 hours, the injected uterine horns of the first 3 pigs were assessed and a pilot appendectomy was performed in the last 2 pigs. RESULTS: Ethanolamine oleate (EO) injected uterine horns demonstrated similarities to the inflamed human appendix. Simulations of the appendectomy were successfully performed by using the EO model. LIMITATIONS: Suboptimal existing tools. CONCLUSIONS: This preliminary study demonstrated the technical feasibility to create a model for acute appendicitis by using the porcine uterine horn and transgastric appendectomy.

Animals↗

The role of mast cells in the pathogenesis of pain in chronic pancreatitis.

BACKGROUND: The biological basis of pain in chronic pancreatitis is poorly understood. Mast cells have been implicated in the pathogenesis of pain in other conditions. We hypothesized that mast cells play a role in the pain of chronic pancreatitis. We examined the association of pain with mast cells in autopsy specimens of patients with painful chronic pancreatitis. We explored our hypothesis further using an experimental model of trinitrobenzene sulfonic acid (TNBS) -induced chronic pancreatitis in both wild type (WT) and mast cell deficient mice (MCDM). METHODS: Archival tissues with histological diagnoses of chronic pancreatitis were identified and clinical records reviewed for presence or absence of reported pain in humans. Mast cells were counted. The presence of pain was assessed using von Frey Filaments (VFF) to measure abdominal withdrawal responses in both WT and MCDM mice with and without chronic pancreatitis. RESULTS: Humans with painful chronic pancreatitis demonstrated a 3.5-fold increase in pancreatic mast cells as compared with those with painless chronic pancreatitis.WT mice with chronic pancreatitis were significantly more sensitive as assessed by VFF pain testing of the abdomen when compared with MCDM. CONCLUSION: Humans with painful chronic pancreatitis have an increased number of pancreatic mast cells as compared with those with painless chronic pancreatitis. MCDM are less sensitive to mechanical stimulation of the abdomen after induction of chronic pancreatitis as compared with WT. Mast cells may play an important role in the pathogenesis of pain in chronic pancreatitis.

Abdomen↗

In vivo gastric and intestinal slow waves in W/WV mice.

The aim was to investigate whether there are regular gastric and intestinal slow waves in conscious W/WV mice. Eleven W/WV mice and 11 wild-type mice were implanted with two pairs of electrodes in the stomach and small intestine. Gastrointestinal slow waves were recorded both under anesthesia and in the conscious state. Atropine and verapamil were given separately to an additional 10 W/WV mice. Results were as follows. (1) The conscious W/WV mice showed lower rhythmic slow waves in the small intestine (77.1 vs 93.5%; P < 0.001). However, the frequency (10.7 vs 18.8 cpm; P < 0.0001) and the antregrade propagation of intestinal slow waves in W/Wv mice were significantly lower than in the controls. In the stomach, regular slow waves were recorded in both groups, with no difference between the two groups. (2) Anesthesia significantly impaired both gastric and intestinal slow waves in both groups. (3) Atropine and verapamil had no effects on the rhythmicity of intestinal slow waves. We conclude that ICC-MY may not be the sole pacemaker cells for slow waves in the small intestine. There may be some abnormality of smooth muscle cells in W/WV mice that causes a reduction in the frequency, rhythmicity, and antegrade propagation of slow waves.

Anesthesia↗

Development of a new access device for transgastric surgery.

Flexible endoscope-based endoluminal and transgastric surgery for cholecystectomy, appendectomy, bariatric, and antireflux procedures show promise as a less invasive form of surgery. Current endoscopes and instruments are inadequate to perform such complex surgeries for a variety of reasons: they are too flexible and are insufficient to provide robust grasping and anatomic retraction. The lack of support for a retroflexed endoscope in the peritoneal cavity makes it hard to reach remote structures and makes vigorous retraction of tissues and organs difficult. There is also a need for multiple channels in scopes to allow use of several instruments and to provide traction/countertraction. Finally, secure means of tissue approximation are critical. The aim was to develop and test a new articulating flexible endoscopic system for endoluminal and transgastric endosurgery. A multidisciplinary group of gastrointestinal physicians and surgeons worked with medical device engineers to develop new devices and instruments. Needs assessments and design parameters were developed by consensus. Prototype devices were tested using inanimate models until usable devices were arrived at. The devices were tested in nonsurvival pigs and dogs. The devices were accessed through an incision in the wall of the stomach and manipulated in the peritoneal cavity to accomplish four different tasks: right upper quadrant wedge liver biopsy, right lower quadrant cecal retraction, left lower quadrant running small bowel, and left lower quadrant exposure of esophageal hiatus. In another three pigs, transgastric cholecystectomy was attempted. The positions of the device, camera, and endosurgical instruments, with and without ShapeLock technology, were recorded using laparoscopy and endoscopy and procedure times and success rates were measured. Instrument design parameters and their engineering solutions are described. Flexible multilumen guides which could be locked in position, including a prototype which allowed triangulation, were constructed. Features of the 18-mm devices include multidirectional mid body and/or tip angulation, two 5.5-mm accessory channels allowing the use of large (5-mm) flexible endosurgical instruments, as well as a 4-mm channel for an ultraslim prototype video endoscope (Pentax 4 mm). Using the resulting devices, the four designated transgastric procedures were performed in anesthetized animals. One hundred percent of the transgastric endosurgical procedures were accomplished with the exception of a 50% success for hiatal exposure, a 90% success rate for wedge liver biopsy, and a 33.3% success rate for cholecystectomy. A new endosurgical multilumen device and advanced instrumentation allowed effective transgastric exploration and procedures in the abdominal cavity including retraction of the liver and stomach to allow exposure of the gallbladder, retraction of the cecum, manipulation of the small bowel, and exposure of the esophageal hiatus. This technology may serve as the needed platform for transgastric cholecystectomy, gastric reduction, fundoplication, hiatus hernia repair, or other advanced endosurgical procedures.

Animals↗

An unusual electrocardiogram artifact: what is its source?

A diabetic female presented with nausea and vomiting. Her electrocardiogram showed sinus rhythm with two artifactual spikes, not synchronized with the cardiac rhythm. The patient had an implanted gastric electrical stimulation system for treating her diabetic gastroparesis. Recent DC shock for ventricular fibrillation during coronary angiography caused malfunction of the gastric pacemaker.

Artifacts↗

Changes of the neuropeptides content and gene expression in spinal cord and dorsal root ganglion after noxious colorectal distension.

Visceral pain/hypersensitivity is a cardinal symptom of functional gastrointestinal disorders. With their peripheral and central (spinal) projections, sensory neurons in the dorsal root ganglia (DRG) are the "gateway" for painful signals emanating from both somatic and visceral structures. In contrast to somatic pain, the neurochemical pathways involved in visceral pain/hypersensitivity have not been well studied. We hypothesized the neuropeptide changes in spinal cord and DRG during visceral pain would mirror similar changes in somatic nociception. Noxious (painful) colorectal distension (CRD) was done by distending a rectal balloon up to 60 mm Hg phasically for 1 h in Sprague-Dawley rats. The spinal content of calcitonin gene-related peptide (CGRP), substance P (SP), galanin and vasoactive intestinal peptide (VIP) as well as their mRNAs in DRG were measured at 0, 4 and 24 h after the CRD. Visceromotor reflex (VMR) was measured by recording the electromyogram at the abdominal muscle in response to CRD. Distal colorectum was removed for evaluating the presence of inflammation. No significant evidence of histological inflammation was seen in the colonic mucosa/submucosa after repeated CRD, which is confirmed by myeloperoxidase assay. The spinal content of CGRP and SP decreased significantly 4 h after CRD, while galanin and VIP levels increased gradually and reached highest level at 24 h (p<0.05). The mRNAs in DRG of the neuropeptides were significantly upregulated after CRD (p<0.05). VMR recording showed the rat's colon became hypersensitive 4 h after CRD, a sequence parallel to the spinal changes of CGRP and SP in timeframe. Noxious mechanical distension of the colorectum causes an acute change in the spinal levels of excitatory neurotransmitters (CGRP and SP), probably reflecting central release of these peptides from sensory neurons and contributing to the hypersensitivity following the noxious CRD. This is followed by a slower change in the levels of the inhibitory neurotransmitter galanin and VIP. Such stimulation results in significant alternation of the gene expression in DRG, reflecting the plasticity of the neuronal response. In the absence of visceral inflammation, the aforementioned neuropeptides are important mediators in the processing of visceral pain/hypersensitivity.

Animals↗

Peroral transgastric endoscopic ligation of fallopian tubes with long-term survival in a porcine model.

BACKGROUND: We have previously reported the feasibility and safety of the peroral transgastric endoscopic approach for diagnostic peritoneoscopy, liver biopsy, and gastrojejunostomy with long-term survival in a porcine model. This approach eliminates incisions of the abdominal wall, providing a less invasive alternative to diagnostic and therapeutic laparoscopy. We now report successful performance of peroral endoscopic transgastric ligation of Fallopian tubes with long-term survival in a porcine model. METHODS: Six female 50-kg pigs had general anesthesia and irrigation of the stomach with an antibiotic solution. Gastric puncture was performed with needleknife electrocautery followed by balloon dilatation of the tract with 20-mm TTS dilating balloon (Microvasive). A standard upper endoscope that underwent high-level disinfection and gas sterilzation was advanced into the peritoneal cavity through a sterile overtube. Both Fallopian tubes were identified and one was ligated using Olympus Endoloops. The other patent tube served as a control. Tubal patency was evaluated by hysterosalpingogram before and after ligation. After a follow-up period of 2-3 weeks, the pigs were sacrificed for postmortem examination. RESULTS: The Fallopian tubes were easily accessed, identified and ligated in all 6 pigs. In each pig, fluoroscopy confirmed complete obstruction of the ligated tube with preserved patency of the other tube. All pigs survived well and ate heartily without any ill-effects. Postmortem examination did not reveal any peritonitis or intra-abdominal adhesions. The Endoloops were in place with complete obstruction of the ligated tubes and patency of the controls. Histopathologic examination of the tubes showed chronic inflammatory infiltrates without abscesses. CONCLUSIONS: The peroral endoscopic transgastric approach to ligation of the Fallopian tubes with long-term survival is technically feasible and safe in a porcine model. The endoscopic transgastric approach to the peritoneal cavity has potential for a wide array of diagnostic and therapeutic procedures.

Animals↗

Endoscopic suturing without extracorporeal knots: a laboratory study.

BACKGROUND: To eliminate cumbersome extracorporeal knotting, we designed a new endoscopic suturing device, the Eagle Claw V. The efficacy of the new device was tested on the Erlangen model and was compared with the initial extracorporeal knotting version (Eagle Claw II). METHODS: Segments of porcine splenic arteries were placed on the mucosal surface of the anterior wall of a pig stomach. The two ends of the artery were brought out through the gastric wall and were connected to a two-channel manometer. The Eagle Claw V has a curved needle with a detachable tip. After puncturing the tissue, the needle tip was engaged into a catching cartridge, where the suture had been embedded in a tightening mechanism. The suture could be tightened by simply pulling the end. The Eagle Claw V was used to plicate the splenic arteries mounted on the stomach. Suturing was considered secure if the suture could withstand endoluminal pressure greater than 200 mm Hg that lasted at least 10 seconds. RESULTS: Eleven of 15 stitches (73.3%) gained secure plication of the vessels. The suturing time (mean +/- standard deviation 2.93 +/- 0.80 minutes) was significantly faster than that of the Eagle Claw II (9.38 +/- 1.51 minutes). The device consistently achieved penetration of the muscular layer, and 4 of 15 sutures included the serosa. The 4 failures were because of suture breakage in two, thread entanglement in one, and cartridge dislodgement in one. CONCLUSIONS: The present prototype represents significant improvements in the ease of operation and the security of the suture, bringing the technique closer to clinical use for a variety of applications.

Animals↗

Eagle Claw II: A novel endosuture device that uses a curved needle for major arterial bleeding: a bench study.

BACKGROUND: Control of bleeding from major arteries in the upper-GI tract remains difficult with currently available endoscopic devices. We designed an endosuture device that uses a curved needle and extracorporeal knotting, and assessed the device in stopping arterial bleeding in a bench model. METHODS: Harvested porcine splenic arteries (2-mm diameter) were tunneled submucosally in pig stomach with the open end protruding into an artificially created mucosal defect. The outer end of the vessel was connected to a pulsatile pump, and red ink was infused at a pressure of about 100 mm Hg. The stomach was installed on an Erlangen endo-training model. The suturing device (Eagle Claw II), mounted outside an endoscope, has an eyed, curved needle that carries a 3-0 nylon thread. After puncture, the thread was retrieved by using a hook. Three-throw square knots were tied at the thread extracorporeally and were pushed into place by using a knotting cap. The criteria of successful plication was defined as hemostasis after knotting, no leakage at pressures of >200 mm Hg, and the vessel was completely encircled by the suture. RESULTS: A total of 25 sutures were made with the mean time of 9.38 minutes (standard deviation 1.51). Control of the bleeding was obtained with 17 sutures (68%). The causes for failure were the following: a suture was too shallow (4), a loose knot (2), incorrect suture position (1), and stomach-wall edema (1). CONCLUSIONS: Control of bleeding from large arteries by using endoscopic suturing is possible. Continued refinements of the device are required.

Animals↗

Endoscopic gastrojejunostomy with survival in a porcine model.

BACKGROUND: We have previously reported the feasibility and the safety of an endoscopic transgastric approach to the peritoneal cavity in a porcine model. We now report successful performance of endoscopic gastrojejunostomy with survival. METHODS: All procedures were performed on 50-kg pigs, with the pigs under general anesthesia, in aseptic conditions with sterilized endoscopes and accessories. The stomach was irrigated with antibiotic solution, and a gastric incision was performed with a needle-knife and a sphincterotome. A standard upper endoscope was advanced through a sterile overtube into the peritoneal cavity. A loop of jejunum was identified, was retracted into the stomach, and was secured with sutures while using a prototype endoscopic suturing device. An incision was made into the jejunal loop with a needle-knife, and the filet-opened ends of the jejunal wall were secured to the gastric wall with a second line of sutures, completing the gastrojejunostomy. OBSERVATIONS: Two pigs survived for 2 weeks. Endoscopy and a radiographic contrast study performed after gastrojejunostomy revealed a patent anastomosis with normal-appearing gastric and jejunal mucosa. Postmortem examination demonstrated a well-healed anastomosis without infection or adhesions. CONCLUSIONS: The endoscopic transgastric approach to create a gastrojejunostomy is technically feasible and can be performed, with survival, in a porcine model.

Animals↗

Improvement of gastric motility with gastric electrical stimulation in STZ-induced diabetic rats.

AIMS: The aims of this study were to observe whether gastric motility was impaired in streptozotocin (STZ)-induced diabetic rats and whether gastric electrical stimulation was able to restore the impaired motility. METHODS: Ten control rats and 30 STZ-induced diabetic rats were used in this study. Gastric slow waves were recorded at baseline and 0, 1, 2, 3 and 4 weeks after the injection of STZ or vehicle. Gastric emptying with (long or short pulses) or without gastric electrical stimulation was measured 6 weeks after STZ injection in a group of 10 diabetic rats each. RESULTS: (1) STZ injection resulted in hyperglycemia and weight loss. (2) Gastric motility was impaired in the diabetic rats. The percentage of normal slow waves was progressively reduced 2 weeks after STZ injection. Compared with the control rats, gastric emptying in the diabetic rats was significantly delayed 6 weeks after STZ injection (60 +/- 3 vs. 79 +/- 2%, p < 0.02). (3) Gastric electrical stimulation with either long or short pulses accelerated gastric emptying in the diabetic rats. (4) Gastric electrical stimulation with long but not short pulses was capable of normalizing gastric dysrhythmia in the diabetic rats. CONCLUSION: Our data show that gastric motility is impaired in STZ-induced diabetic rats as reflected by a progressive reduction in the percentage of normal gastric slow waves and delayed gastric emptying. Moreover, here we show that gastric electrical stimulation normalizes delayed gastric emptying in diabetic rats and this normalization is not attributed to the effect of gastric electrical stimulation on gastric slow waves.

Animals↗

Modulation of TRPV1 by nonreceptor tyrosine kinase, c-Src kinase.

The capsaicin receptor TRPV1 is a nonselective cation channel that is expressed in sensory neurons. In this study, we examined the role of the nonreceptor cellular tyrosine kinase c-Src kinase in the modulation of the rat TRPV1. Capsaicin-induced currents in identified colonic dorsal root ganglion neurons were blocked by the c-Src kinase inhibitor PP2 and enhanced by the tyrosine phosphatase inhibitor sodium orthovandate. PP2 also abolished currents in human embryonic kidney-293 cells transfected with rat TRPV1, whereas cotransfection of TRPV1 with v-Src resulted in fivefold increase in capsaicin-induced currents. In cells transfected with dominant-negative c-Src and TRPV1, capsaicin-induced currents were decreased by approximately fourfold. TRPV1 co-immunoprecipitated with Src kinase and was tyrosine phosphorylated. These studies demonstrate that TRPV1 is a potential target for cellular tyrosine kinase-dependent phosphorylation.

Animals↗

Widespread EMR: a new technique for removal of large areas of mucosa.

BACKGROUND: Widespread EMR is a novel technique for resection of large areas of mucosa as a single bloc. Large lesion size (>2 cm) is a recognized limitation of current EMR techniques. This study assessed the technical feasibility, efficacy, and safety of widespread EMR in a porcine model. METHODS: Widespread EMR was performed in 6 pigs. A submucosal fluid cushion was created in the distal esophagus by using a 0.83% solution of hydroxypropyl methylcellulose. A mucosal strip 5 cm in length and including at least 50% of the luminal circumference was marginated by using a prototype cutting device. The proximal end of the mucosa was stripped from the submucosa by using a grasping forceps. The distal end was snare resected. Resected tissue was assessed histologically. Endoscopy was repeated at weeks 1 and 6. At week 6, a second widespread EMR of the mucosa on the wall opposite the initial resection was attempted to create a full circumferential resection. RESULTS: Widespread EMR was completed in all animals. The esophagus was denuded of mucosa in 5-cm lengths that included 50% of the circumference of the lumen. No procedure-related complication was observed. Histologic assessment demonstrated that the resection specimen included mucosa and submucosa but not muscularis propria. Endoscopy at 1 week revealed mucosal regrowth in two animals and ulceration in 4. At week 6, regrowth of mucosa was noted in all animals. The second wide EMR proved to be technically difficult and was associated with perforation, peri-esophageal abscess, and stricture formation. CONCLUSIONS: Wide EMR appears to be technically feasible for removal of large areas of mucosa. Mucosal strips 5 cm long that included over 50% of the luminal circumference were resected safely. Resection was followed by complete regrowth of the mucosa. However, a second wide EMR to create a circumferential resection proved to be technically difficult and unsafe.

Animals↗

Trypsin mediates nociception via the proteinase-activated receptor 2: a potentially novel role in pancreatic pain.

BACKGROUND & AIMS: The pathogenesis of pain in pancreatitis remains poorly understood. We hypothesized that trypsin, a key inflammatory mediator in this condition, can also activate nociceptive neurons via the proteinase-activated receptor 2. METHODS: Double immunohistochemical staining of T8 to T12 dorsal root ganglia sections was performed with antibodies against proteinase-activated receptor 2 and vanilloid receptor 1, a marker for primary nociceptive neurons. In vivo nociceptive activity was measured by FOS immunoreactivity in thoracic spinal dorsal horn segments after intrapancreatic administration of proteinase-activated receptor 2 agonists. Pain behavior was assessed by visceromotor reflex activity in response to noxious stimulation of the pancreas with proteinase-activated receptor 2 agonists. RESULTS: Proteinase-activated receptor 2 was expressed by virtually all nociceptive neurons in thoracic dorsal root ganglia. Intraductal trypsin, in subinflammatory concentrations, activated spinal dorsal horn neurons in a dose-dependent manner, as measured by FOS expression. Both trypsin and a proteinase-activated receptor 2-specific peptide agonist induced a behavioral pain response when infused into the pancreatic duct of awake rats. Preinfusion of the pancreatic duct with proteinase-activated receptor 2-specific activating peptide desensitized the response to trypsin. CONCLUSIONS: Our findings suggest a novel proteinase-activated receptor 2-mediated role for trypsin in the pathogenesis of pancreatic pain and one that is independent of its inflammatory effect.

Animals↗