芍药苷治疗内脏敏感性肠易激综合征的研究

目的:研究芍药苷对内脏敏感性肠易激综合征(IBS)的治疗作用.方法:经肠道连续6天给予冰醋酸或芥末油,分别建立冰醋酸或芥末油大鼠内脏高敏感性IBS模型,灌胃曲美布丁或芍药苷高、中、低剂量药液,每天1次连续3天,观察各组大鼠肠道内扩张引起腹部抬起和背部拱起的容量阈值,记录大鼠结肠电频率、峰电位、峰峰值和面积.结果:曲美布丁及芍药苷中剂量给药后大鼠肠敏感性显著改善,明显降低两种模型大鼠腹部抬起和背部拱起阈值,降低结肠电频率、峰电位、峰峰值及峰面积.结论:芍药苷可通过降低肠道敏感性,改善结肠电生理活动来治疗内脏高敏感性IBS模型大鼠.     

腹泻型肠易激综合征大鼠模型的建立及敏感性评估的实验研究

目的建立腹泻型肠易激综合征(IBS)大鼠模型并对模型的肠道敏感性进行评估。方法将出生8~21d的大鼠乳鼠给予连续性的直肠内炎症性刺激(直肠注入0.087 mol.L-1醋酸0.5 ml),建立IBS内脏感觉过敏的动物模型,通过观察模型大鼠在直结肠扩张时痛觉阈值的变化以及致痉剂对模型大鼠的离体肠管舒缩运动的影响,研究IBS大鼠模型内脏敏感性的变化。结果第6周和第8周模型组抬腹和拱背的压力阈值明显低于正常组(P<0.01),离体肠管运动实验中,加致痉剂后模型组升高比值均大于正常组,差异有显著性(P<0.05)。结论乳鼠的新生期肠道内的慢性炎症刺激,可以在成年后引起慢性内脏敏感性增高,是一个符合IBS基本特征的动物模型。     

益生菌对肠易激综合征大鼠内脏高敏感性的作用以及肥大细胞-PAR2-TRPV1通路的影响

目的探讨益生菌对肠易激综合征(IBS)大鼠内脏高敏感性的作用以及肥大细胞(MC)-蛋白酶激活受体2(PAR2)-瞬时感受器电位香草酸受体1(TRPV1)轴的影响。方法将30只SD大鼠随机分为空白组、模型组、益生菌组,每组10只。模型组和益生菌组大鼠通过连续6 d醋酸灌肠+束缚应激建立IBS模型。造模成功后,益生菌组大鼠予以双歧杆菌三联活菌胶囊107 CFU/(kg·d)灌胃,1次/d,连用14 d。实验结束时,进行结肠扩张试验(CRD)观察大鼠腹部撤离反射(AWR),检测大鼠粪便含水量及双歧杆菌和大肠埃希菌的比值(B/E值),检测血清5-羟色胺(5-HT)、P物质(SP)、促肾上腺皮质激素释放激素(CRH)水平。甲苯胺蓝染色检测结肠组织MC浸润情况,Western blot法检测脊髓背根神经节(DRG)PAR2和TRPV1蛋白表达量。结果与模型组比较,益生菌组大鼠不同压力扩张情况下AWR评分、粪便含水量、血清5-HT、SP、CRH、IL-12水平、结肠组织MC浸润数量以及DRG组织PAR2和TRPV1蛋白表达量显著降低,而血清IL-10水平和粪便中B/E比值显著升高,差异有统计学意义(P<0.05)。结论益生菌可通过调节肠道菌群紊乱、抑制MC-PAR2-TRPV1轴激活改善IBS大鼠内脏高敏感性,降低炎症反应。     

甘麦大枣汤对焦虑型肠易激综合征大鼠行为学和肠组织中 5-HT、SP、CGRP、TNF-α的影响研究

目的：研究甘麦大枣汤对焦虑型肠易激综合征大鼠5-HT、SP、CGRP和TNF-α含量以及肠组织病理性影响。方法：使用SD大鼠70只,除空白对照组外,各组均以噪音刺激、足底电击、夹尾刺激、束缚和番泻叶提取物灌胃方法,建立焦虑型肠易激综合征大鼠模型,模型随机分5组维持刺激并分别给予相应药物灌胃,连续用药15 d后考察行为学变化和各种IBS大鼠的肠推动,然后处死各实验组大鼠,检测大鼠结肠组织HE染色的病理学变化,使用ELISA试剂盒检测各组大鼠结肠和血清中5-HT、SP、CGRP和TNF-α含量。结果：与模型组相比,甘麦大枣汤能显著降低IBS大鼠焦虑样,但降低肠推动作用较阳性药对照组弱。甘麦大枣汤可降低肠组织和血清中的5-HT、SP和CGRP水平（P<0.05）,其中高剂量组最明显（P<0.01）,但各给药组中的TNF-α相比IBS模型无显著差异。病理分析显示,高剂量组和中剂量组可明显减少IBS大鼠肠组织中炎性反应。结论：甘麦大枣汤对焦虑型肠易激综合征大鼠有治疗效果,其作用机制可能与调节5-HT、SP、CGRP表达有关,对TNF-α相关因子作用不显著。     

甘麦大枣汤对焦虑型肠易激综合征大鼠行为学和肠组织中 5-HT、SP、CGRP、TNF-α的影响研究

目的：研究甘麦大枣汤对焦虑型肠易激综合征大鼠5-HT、SP、CGRP和TNF-α含量以及肠组织病理性影响。方法：使用SD大鼠70只,除空白对照组外,各组均以噪音刺激、足底电击、夹尾刺激、束缚和番泻叶提取物灌胃方法,建立焦虑型肠易激综合征大鼠模型,模型随机分5组维持刺激并分别给予相应药物灌胃,连续用药15 d后考察行为学变化和各种IBS大鼠的肠推动,然后处死各实验组大鼠,检测大鼠结肠组织HE染色的病理学变化,使用ELISA试剂盒检测各组大鼠结肠和血清中5-HT、SP、CGRP和TNF-α含量。结果：与模型组相比,甘麦大枣汤能显著降低IBS大鼠焦虑样,但降低肠推动作用较阳性药对照组弱。甘麦大枣汤可降低肠组织和血清中的5-HT、SP和CGRP水平（P<0.05）,其中高剂量组最明显（P<0.01）,但各给药组中的TNF-α相比IBS模型无显著差异。病理分析显示,高剂量组和中剂量组可明显减少IBS大鼠肠组织中炎性反应。结论：甘麦大枣汤对焦虑型肠易激综合征大鼠有治疗效果,其作用机制可能与调节5-HT、SP、CGRP表达有关,对TNF-α相关因子作用不显著。     

益母草对肠易激综合征内脏感觉过敏大鼠肥大细胞和P物质表达的影响

目的探索益母草调节肠易激综合征(IBS)内脏感觉过敏的可能机制。方法采用结肠慢性刺激法制作内脏高敏性的IBS大鼠模型,将实验动物分为正常组、模型组、益母草组,观察益母草对IBS大鼠AWR评分以及结肠肥大细胞(MC)、P物质(SP)含量的影响。结果与对照组比较,模型组大鼠AWR评分,结肠MC、SP含量都明显升高,而益母草组大鼠AWR评分,结肠MC、SP含量与模型组比较明显降低。结论益母草作用机制可能是通过调节MC、SP的分泌,来降低肠道敏感性。     

肠安颗粒治疗肠易激综合征的药效学研究

目的进行肠安颗粒治疗肠易激综合征(IBS)的药效学研究。方法大鼠60只随机分为空白对照组,模型对照组,匹维溴铵组,肠安颗粒高剂量组(生药28.4g·kg~(-1))、中剂量组(生药14.2 g·kg~(-1))、低剂量组(生药7.1 g·kg~(-1)),采用荧光分七光度法测定血清中5-羟色胺(5-HT)的含量,硝酸还原酶法测定血清中-氧化氮(NO)含量,考察动物体重、血清中5-HT含量变化、血清中NO含量变化,并观察结肠组织的病变情况。结果肠安颗粒高、中、低剂量组对模型大鼠体重下降有明显的改善,与模型对照组比较差异显著(P<0.01),与匹维溴铵组作用相当;肠安颗粒高、中、低剂量均可明显提高血清中5-HT和NO含量;组织学检查结果表明,肠安颗粒高、中剂量可明显改善动物结肠的炎症症状,与模型对照组比较差异显著,与匹维溴铵组无明显差异。结论肠安颗粒可改善IBS大鼠体重与结肠炎症,其原因可能与提高血清中5-HT和NO含量有关。     

肠激安方干预腹泻型IBS模型大鼠SP、CGRP的机制研究

目的研究肠激安方干预腹泻型IBS模型大鼠SP、CGRP的机制。方法对出生后8～21d的大鼠给予连续性的结肠内炎征性刺激,复制IBS内脏感觉过敏的动物模型,观察肠激安方对SP、CGRP的影响。结果肠激安药液能明显改善大鼠的腹泻状况,降低肠道敏感性,高、中、低剂量肠激安药液均能降低模型大鼠结肠黏膜中CGRP、SP阳性纤维的平均OD值,改善肠黏膜表面糜烂、溃疡,与模型组比较差异显著(P<0.01或P<0.05)。结论肠激安方能明显改善大鼠的腹泻状况,降低肠道敏感性,降低模型大鼠结肠黏膜中CGRP、SP阳性纤维的平均OD值水平,改善肠黏膜表面糜烂、溃疡。     

菝葜治疗便秘型肠易激综合征作用机制的实验研究

目的研究菝葜治疗便秘型肠易激综合征的疗效及作用机制。方法用冰水灌胃法复制大鼠便秘型肠易激综合征模型,将造模成功大鼠分为模型组、菝葜提取物高、中、低剂量组(浓度依次为8、4、2 g.ml-1,按生药量计)、阳性对照组,另设空白对照组。灌胃给药3周后,酶免法测定大鼠血清5-HT和血浆SS、SP含量的变化,观察菝葜提取物对大鼠结肠5-HT、SP、SS和脊髓SP免疫组化染色的影响,以及对大鼠结肠MC甲苯胺蓝法染色的影响。结果与模型组相比,菝葜提取物低剂量组能够降低模型大鼠血清5-HT和血浆SS含量(P<0.05);能够升高模型大鼠血浆SP的含量(P<0.05);能够升高模型大鼠结肠SS、SP和脊髓SP免疫组化染色的平均灰度值(P<0.05);能够升高模型大鼠结肠5-HT免疫组化染色平均灰度值(P<0.01);并且能够减少模型大鼠结肠MC计数(P<0.05)。结论菝葜对便秘型肠易激综合征模型大鼠有明显的治疗作用,其作用机制可能是通过调整模型大鼠血清5-HT,血浆SS、SP,结肠5-HT、SP、SS、MC,脊髓SP等来实现的。     

螺环哌嗪盐化合物DXL-A-24对肠易激综合征大鼠内脏高敏感性和肠道菌群的影响

目的:探讨螺环哌嗪盐化合物DXL-A-24对肠易激综合征(irritable bowel syndrome, IBS)大鼠内脏高敏感性和肠道菌群的影响。方法:采用母婴分离联合束缚应激制备IBS大鼠模型，造模成功大鼠随机分为模型组、利那洛肽组(0.022 mg·kg^-1)、螺环哌嗪盐化合物DXL-A-24低、中、高剂量组(2,6,12 mg·kg^-1),每组14只，同时设正常组，连续灌胃28 d。采用腹壁回撤反射评估大鼠内脏敏感性，ELISA法检测结肠组织肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、D-乳酸(D-lactate,D-LA)和二胺氧化酶(diamine oxidase, DAO)含量，免疫组化法检测结肠组织P物质(substance P,SP)和降钙素基因肽(calcitonin gene-related peptide, CGRP)的表达，16S rRNA基因测序分析肠道菌群的变化。结果:与正常组相比，模型组大鼠毛发稀疏发黄，攻击性强，肛周有粪便污染，内脏敏感性明显升高(P<0.05)。与...     

Effect of ginseng saponins on a rat visceral hypersensitivity model

The 5-hydroxytryptamine3A (5-HT3) receptor is closely related with irritable bowel syndrome (IBS) in enteric nervous systems. We previously demonstrated that ginseng total saponins (GTS, also called ginsenosides), the active ingredients of Panax ginseng, inhibit the activity of 5-HT3A receptor channels expressed in Xenopus laevis oocytes. Here, we further investigated whether the in vitro inhibitory effect of ginsenosides on 5-HT3A receptor channel activity is coupled to in vivo attenuation of IBS. A rat model of IBS was induced by colorectal distention (CRD) and intracolonic infusion of 0.6% acetic acid (CRD-acetic acid), and visceral hypersensitivity was assessed by counting the contractions in the external oblique muscles of conscious rats during the 10 min distention period. We found that oral administration of GTS significantly and dose-dependently inhibited CRD-acetic acid-induced visceral hypersensitivity. The EC50 was 5.5+/-4.7 mg/kg (95% confidence intervals: 1.2-15.7) and the inhibitory effect of GTS against visceral hypersensitivity persisted for 4 h. When we compared the effects of protopanaxadiol (PD) ginsenosides and protopanaxatriol (PT) ginsenosides against CRD-acetic acid-induced visceral hypersensitivity, we found that PT but not PD ginsenosides significantly attenuated the CRD-acetic acid-induced visceral hypersensitivity. These results indicate that PT ginsenosides of Panax ginseng might be the main active components for the attenuation of experimentally CRD-acetic acid-induced visceral hypersensitivity, and may be clinically relevant for the future treatment of IBS.     

枳实槟榔散对大鼠肠道高敏感性的影响及其作用机制研究

目的观察枳实槟榔散对大鼠肠道高敏感性的影响及其可能的作用机制。方法采用醋酸慢性刺激乳鼠建立肠道高敏感性大鼠模型,观察枳实槟榔散对大鼠肠道敏感性以及结肠黏膜P物质、5-羟色胺（5-HT）免疫反应阳性纤维的影响。结果枳实槟榔散组的低与高剂量组的痛阈值和最大耐受疼痛阈值与模型组比较有明显升高（P〈0.05）;肠道内P物质含量高于模型组（P〈0.01）,肠道黏膜下的5-HT免疫阳性神经元/神经纤维阳性指数（IOD）显著性减少（P〈0.01）。结论枳实槟榔散可降低大鼠肠道高敏感性,其作用机制可能与引起5-HT免疫阳性神经纤维减少、改善P物质分泌紊乱有关。     

Drug treatment options for irritable bowel syndrome: managing for success

Irritable bowel syndrome (IBS) is a functional gut disorder the diagnosis of which is based on clinical symptoms as set forth by the Rome criteria. As the population ages, especially with the population of patients >75 years of age expanding greatly over the next 10 years, IBS is becoming one of the most common diseases of the elderly. Thus far, developing treatment strategies for patients with IBS has been difficult because of the lack of pharmacological targets and the wide range of symptomatology. Additionally, demonstration of a therapeutic benefit is difficult in the presence of a high placebo response observed regardless of the therapy employed. Fibre, antidiarrhoeals and antispasmodics all play some role in the symptomatic treatment of IBS. With the evolution of IBS as a disorder of visceral hypersensitivity, new drugs have been developed that target the enteric nervous system. Tricyclic antidepressants (TCAs) have been found to target the enteric neurons and play a role in pain modulation. Currently, the TCAs are recommended only for severe cases of IBS pain. The newest class of drugs to be approved for use in IBS are the serotonin (5-hydroxytryptamine; 5-HT) antagonists. Specifically, the 5-HT3 receptor antagonists have been shown to decrease symptoms in female patients with IBS. A related class of drugs, the 5-HT4 receptor agonists, is being developed for the treatment of constipation-predominant IBS. Further investigation into the role of spinal afferent neurons in visceral hypersensitivity is at the forefront of IBS research. Several experimental drug therapies for IBS are also discussed in this review including N-methyl-D-aspartate receptor antagonists, neurokinin-1 receptor antagonists, octreotide, clonidine and the selective M3 receptor antagonist, zamifenacin.     

APETx2及粪菌移植对母婴分离诱导肠易激综合征大鼠内脏敏感性的影响及机制

目的 探讨粪菌移植对母婴分离诱导的肠易激综合征（IBS）大鼠内脏敏感性的影响并观察酸敏感离子通 道3（ASIC3）抑制剂APETx2对其作用及可能机制。方法 取SD孕鼠10只,待其生产后取仔鼠,采用母婴分离法构 建IBS模型,收集建模成功的大鼠粪便制成粪菌液。18只健康雄性SD大鼠按照随机数字表法分为正常对照（Con） 组、母婴分离（NMS）组、NMS+APETx2 处理组,每组 6 只。NMS 组、NMS+APETx2 组均予以含有抗生素的鸡尾酒 （ABX-water）连续灌胃5 d,构建伪无菌鼠模型,之后给予NMS大鼠粪菌液（1.6 mL/kg）灌胃;Con组给予等体积生理盐 水灌胃,每天1次,连续灌胃5 d。灌胃结束后,NMS+APETx2组给予100 μg/kg APETx2连续腹腔注射7 d,每天1次。 采用墨汁推进实验测定肠道推进率,结直肠扩张刺激后评估内脏敏感性。免疫组化染色法检测结肠组织中ASIC3、 c-kit蛋白表达。分离3组大鼠结肠cajal间质细胞（ICC）,显微镜观察细胞形态学和数量变化。结果 与Con组比较, NMS组肠道推进率减慢,腹部回撤反射（AWR）评分升高,内脏敏感性增加,结肠组织ASIC3、c-kit表达上调,ICC形态 改变。与NMS组相比,NMS+APETx2组肠道推进率加快,AWR评分下降,内脏敏感性降低,结肠组织ASIC3、c-kit表 达下调,ICC形态趋于正常,数量明显减少。结论 IBS粪菌移植可以诱导内脏高敏感发生和降低肠道传输速率, APETx2可改善其内脏敏感性和肠道传输速率,其机制可能与APETx2下调ASIC3表达、抑制与ICC相关的c-kit信号 有关。     

Irritable bowel syndrome: new agents targeting serotonin receptor subtypes

Although the past few years have seen an exponential growth of compounds of potential interest for the treatment of functional gastrointestinal (GI) tract disorders, the gap that still exists between basic and clinical research is easily noticed if one considers the relative paucity of drugs that have received marketing authorisation for the treatment of irritable bowel syndrome (IBS). Traditional efficacy outcomes in drug development for IBS include the ability of the compound to affect GI tract motility (i.e. to exert a prokinetic or an antispasmodic effect), which is thought to be of importance if a motor disorder is the underlying pathophysiological mechanism. More recently, altered visceral sensitivity to a distending stimulus has been suggested to be a key pathophysiological feature, at least in some patients, and has become a target for therapeutic interventions. However, there is now growing consensus that the primary outcome measure in the treatment of functional disorders are those that reflect overall control of the patient's symptoms (pain, diarrhoea, constipation) in everyday situations such as the clinical global improvement scales. Although, in general, guidelines on the design of treatment trials for functional GI tract disorders advise against subcategorisation of patients according to the main symptom (because of symptom instability), subcategorisation indeed makes sense especially in IBS (constipation- or diarrhoea-predominant). Compounds with a specific indication for each subpopulation of patients are now emerging. The rationale for investigations on serotonin (5-hydroxytryptamine; 5-HT) receptor ligands in IBS rests mainly on the fact that serotonin, which may be released by enterochromaffin-like cells in the GI tract as well as from other sources, has a number of well documented motor effects on the GI tract and can produce hyperalgesia in several experimental models. Serotonin receptors belonging to the 5-HT3 and 5-HT4 subtype are the most extensively studied in gastroenterology, although hitherto 'orphan' receptor subtypes, such as the 5-HT7 and the 5-HT(1B/D) receptors, are now emerging. Among 5-HT3 receptor antagonists, alosetron was recently approved for the treatment of diarrhoea-predominant IBS and is an example of a compound that, at least theoretically, may act at multiple levels: by inhibiting visceral sensitivity, by increasing compliance, and by inhibiting excitatory 5-HT3 receptors located on both ascending and descending neuronal pathways involved in peristalsis. For this reason, 5-HT3 receptor antagonists may slow transit, hence the specific indication of alosetron in diarrhoea-predominant IBS. However, alosetron has been recently withdrawn by the manufacturer because of safety concerns. Hypomotility remains an attractive therapeutic target in IBS and the new generation of prokinetics includes several partial agonists at the 5-HT4 receptor, such as tegaserod (HTF-919) and prucalopride (R0-93877). In addition, preliminary evidence suggests that 5-HT4 receptors may also be involved in the modulation of visceral sensitivity. Second-generation 5-HT4 receptor agonists seem to be devoid of the QT-prolonging effects observed in some clinical circumstances with cisapride and may be more active at the colonic level. Piboserod (SB-207266A) is a 5-HT4 receptor antagonist under development for the treatment of diarrhoea-predominant IBS. Finally, interest in 5-HT7 and 5-HT(1B/D) receptor subtypes stems from the observation that the former receptors mediate smooth muscle relaxation (at least in the human colon), whereas sumatriptan (a 5-HT(1B/D) receptor agonist) can affect GI tract motility and visceral sensitivity.     

前胡提取物对抑郁症模型大鼠脑内中枢单胺类神经递质的影响研究

目的：研究前胡提取物中香豆素类化合物对抑郁症模型大鼠脑内中枢单胺类神经递质的影响。方法以孤养加慢性轻度不可预见性应激方法建立大鼠抑郁症模型,测定糖水消耗、敞箱行为及跳台行为来进行行为学评分,并采用高效液相－电化学方法检测其脑内单胺类神经递质的含量,观察模型大鼠给药前后的变化。结果抑郁症模型组大鼠体质量增长缓慢,蔗糖水消耗量明显下降,水平活动和垂直活动均显著下降,跳台错误次数增加,脑内的去甲肾上腺素、5－羟色胺含量降低（P＜0．05）。30mg／（kg? d）、50mg／（kg? d）剂量前胡提取物能显著改善模型大鼠的行为学变化,增加其脑内去甲肾上腺素、5－羟色胺含量（ P＜0．05）。结论前胡提取物中香豆素类化合物具有抗抑郁作用,对中枢单胺类神经递质的调节作用是其作用机制之一。     

5-HT(2B) receptors play a key role in mediating the excitatory effects of 5-HT in human colon in vitro

1. 5-Hydroxytryptamine (5-HT) is known to produce a number of different effects in the gastrointestinal tract of various species, and has been proposed to play a key role in a number of intestinal disorders in man, including irritable bowel syndrome (IBS), although the receptors involved have yet to be established. The aim of the present study was to investigate the distribution and function of 5-HT(2B) receptors in human colon, and to establish their possible role in the aetiology of IBS. 2. The distribution of 5-HT(2B) receptor mRNA and protein were investigated by quantitative RT - PCR, Western analysis and immunocytochemistry. High levels of both mRNA and protein for 5-HT(2B) receptors were found throughout the human gastrointestinal tract, and in particular in colon, where 5-HT(2B) receptors were found predominantly in the longitudinal and circular smooth muscle layers within the muscularis externa, and in the myenteric nerve plexus lying between these two layers. 3. Electrical field stimulation of longitudinal muscle preparations of human colon mounted in organ baths resulted in neuronally-mediated contractile responses, that were significantly potentiated by application of 5-HT (up to 10(-7) M), with a pEC(50) of 8.2 +/- 0.1 (n=49 donors). The response to 5-HT was inhibited by a number of selective 5-HT(2B) receptor antagonists. 4. This study has shown for the first time that, in contrast to animal studies, the excitatory effects of 5-HT in human colon are mediated by 5-HT(2B) receptors. It is proposed that these receptors contribute to the putative 5-HT-induced colonic smooth muscle hypersensitivity associated with IBS.     

Recent advances in pharmacological research on the management of irritable bowel syndrome

Irritable bowel syndrome (IBS), a common gastrointestinal (GI) disorder, is associated with various factors, including lifestyle, infection, stress, intestinal flora, and related diseases. The pharmacotherapeutic stimulation of receptors and downstream signaling pathways is effective in reducing IBS symptoms; however, it is still associated with adverse effects. Various receptors related to GI motility and visceral hypersensitivity should be considered to enhance the benefit/risk ratio of IBS treatments. This review discusses recent pharmacological advances in IBS management. Several receptors related to GI motility and abdominal pain are investigated in various angles. 5-Hydroxytryptamine (5-HT) is an important neurotransmitter that activates the colonic mucosal 5-HT₄ receptor without causing severe cardiovascular adverse effects. The clinical potential of ramosetron for diarrhea-predominant IBS has been suggested because of a lower risk of ischemic colitis than conventional 5-HT₃ receptor antagonists. Toll-like receptors (TLRs), especially TLR2 and TLR4, show a significant effect on the post-infection symptoms and lipopolysaccharide-mediated regulation of GI motility. Histamine is a well-known nitrogenous compound that regulates inflammatory responses and visceral hypersensitivity. Histamine 1 receptor-mediated sensitization of the transient receptor potential vanilloid 1 is associated with IBS. Pharmacological approaches based on these signaling pathways could be useful in the development of novel IBS treatments.