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首页> 外文期刊>The Internet Journal of Pharmacology >Effect Of Buspirone On Inflammation, Pain And Gastric Injury In Mice
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Effect Of Buspirone On Inflammation, Pain And Gastric Injury In Mice

机译：丁螺环酮对小鼠炎症，疼痛和胃损伤的影响

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Buspirone, a 5HT1A receptor partial agonist, was evaluated in various acute nociceptive pain models, on the carrgaeenan-induced paw oedema, in Porsolt's forced-swimming test, on haloperidol-induced catalepsy, on the indomethacin-induced gastric mucosal damage and on gastric acid secretion in mice. Buspirone (2, 4 or 8 mg/kg, i.p.) significantly increased the response latency in the mouse hot plate test. The anti-nociceptive activity was observed with 2 mg/kg and a maximal increase in hot-plate latency by 41.3%. Buspirone in addition markedly increased the nociceptive thresholds in the acetic-acid-induced writhing assay, in the capsaicin-induced chemogenic pain and in electrically-induced pain in mice. It displayed no antidepressant activity in the Porsolt's forced-swimming test, but at doses of 8 or 16 mg/kg, buspirone decreased the duration of catalepsy induced by haloperidol by 28.1 and 58.3%, respectively. When given 30 min prior to subplantar carrageenan injection, the drug at 8, 16 mg/kg, inhibited paw oedema response 4 h post-carrageenan by 26.3, 41.6%, respectively. Buspirone (2, 4 or 8 mg/kg, i.p.) significantly inhibited the development of indomethacin gastric mucosal lesions and gastric acid secretion in a dose-dependent manner. In conclusion, Buspirone increased pain threshold in models of thermal, chemogenic, electrical and visceral pain and displayed anti-inflammatory and gastric protective properties. The drug might prove of value for the management of inflammatory painful conditions. Introduction 5-Hydroxytryptamine 1A (5-HT1A) receptors are important targets for the treatment of mood disorders (1,2) . Buspirone, is a partial 5-HT1A receptor agonist buspirone which is widely used for treating anxiety (3) . 5-HT1A receptors are located presynaptically on cell bodies in the raphe nuclei (somatodendritic receptors) and postsynaptically in 5-HT forebrain projecting areas. By activating somatodendritic receptors, 5-HT and 5-HT1A receptor agonists decrease the firing of 5-HT neurons in the raphe, and, consequently decrease 5-HT terminal release (4) . Drugs acting on 5-HT receptors and enhancing serotonergic neurotransmission e.g., the serotonin reuptake inhibitors clomipramine (5,6) and fluoxetine (7,8,9) have been shown to exhibit analgesic and anti-inflammatory activity in animal models. Data suggest that a tonic release of serotonin in the spinal cord may occurs during ongoing peripheral inflammation, modulating the neurogenic component of oedema either by an inhibitory action on 5-HT1 receptors or by a stimulatory action on 5-HT2 receptors (10) . Serotonin reuptake inhibitors, however, displayed gastric irritant properties and increased gastric acid secretion in experimental animals (11,12) , while reports of increased gastric bleeding events have been reported in humans (13) . In the present study we describe the effects of buspirone in animal models of pain and acute inflammation. In addition, the effects of the compound in Porsolt's forced-swimming test, on haloperidol-induced catalepsy, on gastric acid secretion and on gastric mucosal damage caused by indomethacin, a non-steroidal anti-inflammatory drug (NSAID) commonly used in many arthritic and inflammatory conditions was evaluated. Materials and methods AnimalsSwiss albino mice weighing 20-25 g of body weight (National Research Centre, Cairo) were used. They were housed under standardized conditions with free access to food and water. All animal procedures were performed in accordance with the recommendations for the proper care and use of laboratory animals. Equal groups of 6 mice/group were used in all experiments. The doses of buspirone employed in the study were based upon the human dose after conversion to that of rat according to Paget and Barnes conversion tables (14) .Tests of nociceptionHot-plate assayThe hotplate test was performed on mice by using an electronically controlled hotplate (Ugo Basile, Italy) heated to 52°C (± 0.1°C) (15) . The cut-of
机译：在多种急性伤害性疼痛模型中，在角叉菜胶引起的爪水肿，波索尔特强制游泳试验，氟哌啶醇引起的僵直性发作，吲哚美辛引起的胃黏膜损伤和胃酸方面，对5HT1A受体局部激动剂丁螺环酮进行了评估。在小鼠体内分泌。丁螺环酮（2、4或8 mg / kg，腹膜内）在小鼠热板试验中显着增加了反应潜伏期。以2 mg / kg观察到了抗伤害感受活性，热板潜伏期最大增加了41.3％。此外，丁螺环酮在小鼠的乙酸诱导的扭体试验，辣椒素诱导的化学性疼痛和电诱导性疼痛中显着提高了伤害性阈值。在Porsolt的强迫游泳试验中，它没有显示出抗抑郁活性，但是在8或16 mg / kg的剂量下，丁螺环酮分别使氟哌啶醇引起的僵住症的持续时间减少了28.1和58.3％。在足底角叉菜胶注射前30分钟给予时，该药物以8、16 mg / kg的剂量在角叉菜胶后4 h抑制爪水肿反应分别为26.3、41.6％。丁螺环酮（2、4或8 mg / kg，腹腔注射）以剂量依赖性方式显着抑制消炎痛胃粘膜病变的发展和胃酸分泌。总之，丁螺环酮在热，化学原性，电和内脏痛模型中增加了疼痛阈值，并显示出抗炎和胃保护特性。该药物可能证明对炎性疼痛病症的治疗具有价值。前言5-羟色胺1A（5-HT1A）受体是治疗情绪障碍的重要靶标（1,2）。丁螺环酮是一种5-HT1A受体激动剂丁螺环酮，已广泛用于治疗焦虑症（3）。 5-HT1A受体突触位于突触核的细胞体上（体树突状受体），而突触后位于5-HT前脑投射区域。通过激活体树突状受体，5-HT和5-HT1A受体激动剂可降低缝隙中5-HT神经元的放电，从而降低5-HT末端释放（4）。作用于5-HT受体并增强5-羟色胺能神经传递的药物，例如5-羟色胺再摄取抑制剂氯米帕明（5,6）和氟西汀（7,8,9）在动物模型中显示出镇痛和抗炎活性。数据表明5-羟色胺在脊髓中的滋补释放可能在进行中的周围炎症期间发生，通过对5-HT1受体的抑制作用或对5-HT2受体的刺激作用来调节水肿的神经源性成分（10）。然而，5-羟色胺再摄取抑制剂在实验动物中表现出胃刺激性和胃酸分泌增加（11，12），而人类胃出血事件增加的报道（13）。在本研究中，我们描述了丁螺环酮在疼痛和急性炎症的动物模型中的作用。此外，该化合物在Porsolt的强迫游泳试验中对氟哌啶醇引起的僵直症，胃酸分泌以及吲哚美辛（一种在许多关节炎患者中常用的非甾体抗炎药）引起的胃粘膜损害的作用。并评估了炎症状况。材料和方法动物使用体重20-25克体重的瑞士白化病小鼠（开罗国家研究中心）。他们被安置在标准条件下，可以自由获得食物和水。按照正确护理和使用实验动物的建议执行所有动物程序。在所有实验中均使用6只小鼠/组的相等组。本研究中使用的丁螺环酮的剂量是根据Paget和Barnes转换表根据转化为大鼠的人体剂量计算的（14）。伤害性试验的热板试验热板试验通过使用电子控制的热板对小鼠进行（意大利Ugo Basile）加热到52°C（±0.1°C）（15）。截止

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