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Studies of visceral pain: measurements of stimulus intensity and duration associated with the onset of pain in esophagus, ileum and colon.内脏痛研究：与食管、回肠和结肠疼痛发作相关的刺激强度和持续时间的测量
J Clin Invest. 1958 Jan;37(1):28-34. doi: 10.1172/JCI103581.
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The pharmacological properties of the novel selective 5-HT3 receptor antagonist, alosetron, and its effects on normal and perturbed small intestinal transit in the fasted rat.新型选择性5-羟色胺3（5-HT3）受体拮抗剂阿洛司琼的药理特性及其对禁食大鼠正常和紊乱的小肠转运的影响。
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Central modulation of rectal distension-induced blood pressure changes by alosetron, a 5-HT3 receptor antagonist.5-羟色胺3受体拮抗剂阿洛司琼对直肠扩张诱导的血压变化的中枢调节作用
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Proximal colon distention increases Fos expression in the lumbosacral spinal cord and activates sacral parasympathetic NADPHd-positive neurons in rats.近端结肠扩张可增加大鼠腰骶脊髓中Fos的表达，并激活骶副交感神经NADPHd阳性神经元。
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Common patterns of increased and decreased fos expression in midbrain and pons evoked by noxious deep somatic and noxious visceral manipulations in the rat.大鼠中脑和脑桥中由有害深部躯体和有害内脏操作诱发的fos表达增加和减少的常见模式。
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Desensitization follows excitation of bladder primary afferents by intravesical capsaicin, as shown by c-fos activation in the rat spinal cord.膀胱内注入辣椒素使膀胱初级传入神经兴奋后会出现脱敏现象，这在大鼠脊髓中的c-fos激活中得到了证实。
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5-羟色胺(3)受体拮抗剂阿洛司琼可抑制麻醉大鼠结肠扩张诱导的降压反应和脊髓c-fos表达。

The 5-HT(3) receptor antagonist alosetron inhibits the colorectal distention induced depressor response and spinal c-fos expression in the anaesthetised rat.

作者信息

Kozlowski C M, Green A, Grundy D, Boissonade F M, Bountra C

机构信息

Neuroscience Unit, GlaxoWellcome Research and Development, Stevenage SG1 2NY, UK.

出版信息

Gut. 2000 Apr;46(4):474-80. doi: 10.1136/gut.46.4.474.

DOI:10.1136/gut.46.4.474
PMID:10716675
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1727898/
Abstract

BACKGROUND

Noxious intestinal distention elicits a reflex depressor response in the sodium pentobarbitone anaesthetised rat, which can be used as an index of visceral nociception. 5-HT(3) receptor antagonists inhibit this reflex. Repeated colorectal distention (CRD) induces Fos like immunoreactivity (Fos-LI) in the rat spinal cord.

AIMS

To examine the effect of the 5-HT(3) receptor antagonist alosetron on the depressor response to CRD, and on Fos expression in the lumbosacral spinal cord.

METHODS

Male rats were anaesthetised with sodium pentobarbitone, and mean arterial blood pressure monitored during repeated colorectal balloon inflation before and after treatment with alosetron or saline. Rats anaesthetised with urethane and treated with alosetron or saline underwent a repeated CRD paradigm, after which the lumbosacral spinal cord was removed and processed for visualisation of Fos-LI.

RESULTS

CRD elicited reproducible, volume dependent falls in arterial blood pressure, and repeated distention-effect curves were constructed. Alosetron (1-100 microg/kg intravenously) inhibited the depressor response to CRD in a dose related manner, with an ID(50) value of 3.0 microg/kg. Following repeated CRD, numbers of Fos-LI neurones were significantly increased to 1246 (total in 12 sections at 120 microm intervals from L6 to S1) compared with 49 in sham distended animals. Pretreatment with alosetron (100 microg/kg) significantly reduced numbers of Fos-LI neurones to 479.8.

CONCLUSION

The 5-HT(3) receptor antagonist alosetron inhibits the depressor response to CRD in a potent and dose dependent manner. It also inhibits CRD induced Fos-LI in the spinal cord. These results suggest that 5-HT(3) receptors are involved in visceral nociceptive transmission, perhaps located on primary afferent or spinal neurones.

摘要

背景

在戊巴比妥钠麻醉的大鼠中，有害的肠道扩张会引发反射性降压反应，该反应可作为内脏痛觉的指标。5-羟色胺（5-HT）3受体拮抗剂可抑制此反射。反复结直肠扩张（CRD）可诱导大鼠脊髓中Fos样免疫反应性（Fos-LI）。

目的

研究5-HT3受体拮抗剂阿洛司琼对CRD降压反应及腰段脊髓Fos表达的影响。

方法

雄性大鼠用戊巴比妥钠麻醉，在阿洛司琼或生理盐水处理前后，重复进行结直肠球囊充气时监测平均动脉血压。用乌拉坦麻醉并用阿洛司琼或生理盐水处理的大鼠接受重复CRD范式，之后取出腰段脊髓并进行处理以观察Fos-LI。

结果

CRD引起可重复的、与容量相关的动脉血压下降，并构建了重复扩张效应曲线。阿洛司琼（静脉注射1-100微克/千克）以剂量相关方式抑制对CRD的降压反应，半数抑制剂量（ID50）值为3.0微克/千克。反复CRD后，Fos-LI神经元数量显著增加至1246个（从L6到S1以120微米间隔的12个切片中的总数），而假扩张动物中为49个。阿洛司琼（100微克/千克）预处理显著将Fos-LI神经元数量减少至479.8个。

结论

5-HT3受体拮抗剂阿洛司琼以强效且剂量依赖的方式抑制对CRD的降压反应。它还抑制CRD诱导的脊髓Fos-LI。这些结果表明5-HT3受体参与内脏痛觉传递，可能位于初级传入或脊髓神经元上。