Surgical intestinal manipulation increases gene expression of TrkA, <scp>CGRP</scp>, and <scp>PAR</scp>‐2 <scp>IN</scp> dorsal root ganglia in the rat

Berdún, Sergio; Rychter, Jakub; Vergara, P.

doi:10.1111/nmo.12777

Cited by 2 publications

(2 citation statements)

References 36 publications

(69 reference statements)

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“…The protective effect of NK 1‐3 receptor antagonists against gut dysmotility in early POI has been previously tested [6]. Experiments were performed approximately 1.5 h after surgical intervention, which corresponds to a maximum inhibition of smooth muscle contractility in the manipulated small intestine, before the influx of the inflammatory cells (first wave inhibition) [7,8]. Twenty‐four hours post‐surgery, a clinically relevant peak of gut motility inhibition occurs.…”

Section: Introductionmentioning

confidence: 99%

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Tachykinin antagonists ameliorate surgically induced impairment of gastrointestinal motility in rats

Umer

Ługowska-Umer

Schönborn‐Kellenberger³

et al. 2020

Fundamemntal Clinical Pharma

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The protective effects of tachykinin receptor antagonists: SR140333 (NK1 receptor), SR48968 (NK2 receptor), and SB222200 (NK3 receptor) were tested in rats against a surgically induced postoperative inhibition of gut motility, a common complication of abdominal surgery. The small intestinal transit of Evans blue was measured 24‐h post‐surgery in untreated rats and animals subjected to skin incision, laparotomy, or laparotomy followed by gut evisceration and manipulation. Surgical procedures were conducted under diethyl ether anesthesia. In comparison to untreated and ether‐anesthetized rats, animals undergoing skin incision, laparotomy, or laparotomy with gut evisceration and manipulation showed a significant decrease in the intestinal transit of Evans blue. The pretreatment with NK1 (3–100 µg/kg), NK2 (3–30 µg/kg), and NK3 (10–300 µg/kg) blockers before surgery ameliorated the inhibitory effects of gut manipulation in a dose‐dependent manner. Moreover, the submaximal and maximal doses of NK3 antagonists showed a trend toward reversing not only the inhibition caused by gut manipulation but also laparotomy. An additive effect of combining submaximal doses of NK1‐3 blockers was observed in animals pretreated with NK1 + NK2 compared to single‐agent NK1 and NK2. Additionally, doublets: NK1 + NK3 or NK2 + NK3 and a triplet: NK1 + NK2 + NK3 proved to be more effective than NK2 antagonist alone. In contrast, NK1‐3 blockers have not markedly affected the intestinal propulsion in untreated rats or animals subjected to skin incision or laparotomy. NK1‐3 blockers ameliorated the suppressed small‐bowel gut motility 24 post‐surgery. Combined pretreatment with NK1‐3 antagonists provided selective, additive benefits compared to single agents.

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Section: Introductionmentioning

confidence: 99%

“…Twenty‐four hours post‐surgery, a clinically relevant peak of gut motility inhibition occurs. It is brought about by the influx of monocytes and neutrophils into the muscularis mucosa (second‐wave inhibition) corresponding to the late phase of POI [7–9].…”

Section: Introductionmentioning

confidence: 99%

Tachykinin antagonists ameliorate surgically induced impairment of gastrointestinal motility in rats

Umer

Ługowska-Umer

Schönborn‐Kellenberger³

et al. 2020

Fundamemntal Clinical Pharma

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Electroacupuncture Relieves Visceral Hypersensitivity by Inactivating Protease‐Activated Receptor 2 in a Rat Model of Postinfectious Irritable Bowel Syndrome

Yuan

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Background The role of protease-activated receptor 2 (PAR2) in the analgesic effect of electroacupuncture (EA) on visceral hypersensitivity (VH) in postinfectious irritable bowel syndrome (PI-IBS) has yet to be elucidated. Aim In this study, we investigated the molecular mechanisms underlying the analgesic effect of EA in a rat model of PI-IBS. Methods Visceral hypersensitivity was evaluated by the abdominal withdrawal reflex test before and after administration of the PAR2 agonist, PAR2-AP, and/or EA. The protein expression and mRNA levels of PAR2, CGRP, SP, and TPSP in colon tissues were measured by immunofluorescence, western blot, and RT-PCR. Results We found that EA could alleviate VH and significantly decrease protein and mRNA levels of PAR2, TPSP, CGRP, and SP in PI-IBS rats. The analgesic effect of EA on VH was slightly reduced in the presence of PAR2-AP. Conclusions These results suggest that EA alleviates VH symptoms through downregulation of the levels of the TPSP/PAR2/SP/CGRP signaling axis in colon tissues in PI-IBS rats. Together, our data suggests that PAR2 plays a critical role in the analgesic effect of EA on VH in PI-IBS.

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Surgical intestinal manipulation increases gene expression of TrkA, CGRP, and PAR‐2 IN dorsal root ganglia in the rat

Abstract: Postoperative ileus is accompanied by activation of CGRP, NGF-TrkA, and PAR-2 in DRGs. Our results suggest that these mediators could be a target in further POI studies in order to find new therapeutic targets for this medical condition.

Cited by 2 publications

References 36 publications

Tachykinin antagonists ameliorate surgically induced impairment of gastrointestinal motility in rats

Tachykinin antagonists ameliorate surgically induced impairment of gastrointestinal motility in rats

Electroacupuncture Relieves Visceral Hypersensitivity by Inactivating Protease‐Activated Receptor 2 in a Rat Model of Postinfectious Irritable Bowel Syndrome

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