Lynn P A, Chen B N, Zagorodnyuk V P, Costa M, Brookes S J H
Dept. of Human Physiology and Centre for Neuroscience, Flinders Univ., Bedford Park, SA 5042, Australia.
Am J Physiol Gastrointest Liver Physiol. 2008 Oct;295(4):G862-71. doi: 10.1152/ajpgi.00585.2007. Epub 2008 Aug 28.
The effects of trinitrobenzene sulfonic acid (TNBS)-induced inflammation on specialized, low-threshold, slowly adapting rectal mechanoreceptors were investigated in the guinea pig. Under isoflurane anesthesia, 300 microl saline or TNBS (15 mg/ml) in 30% ethanol was instilled 7 cm from the anal sphincter. Six or 30 days later, single unit extracellular recordings were made from rectal nerve trunks in flat-sheet in vitro preparations attached to a mechanical tissue stretcher. TNBS treatment caused macroscopic ulceration of the rectal mucosa at 6 days, which fully resolved by 30 days. Muscle contractility was unaffected by TNBS treatment. At 6 days posttreatment, responses of low-threshold rectal mechanoreceptors to circumferential stretch were increased, and the proportion of afferents responding with von Frey hair thresholds <or=0.1 mN and mechanoreceptor excitability in response to electrical stimulation were increased in TNBS-treated tissue, suggesting increased sensitivity of the mechanotransducer. Mechanoreceptor function at 30 days posttreatment was in most cases unchanged. The inflammatory mediator prostaglandin E(2) (1 microM) activated mechanoreceptors (6 days) in conjunction with contractile activity, but capsaicin (1 microM) failed to activate mechanoreceptors. Bradykinin (1 microM) activated mechanoreceptors independently of contractile activity and responses to stretch were increased in the presence of bradykinin. Both capsaicin and bradykinin activated unidentified stretch-insensitive afferents independently of contractile activity. Mechanoreceptor function is modulated at 6 days posttreatment but not at 30 days, suggesting a moderate increase in mechanoreceptor sensitivity in inflamed tissue but not after recovery. Other unclassified stretch-insensitive afferents are responsive to inflammatory mediators and capsaicin and may be involved in aspects of visceral sensation.
在豚鼠中研究了三硝基苯磺酸(TNBS)诱导的炎症对特殊的、低阈值、慢适应性直肠机械感受器的影响。在异氟烷麻醉下,将300微升生理盐水或含30%乙醇的TNBS(15毫克/毫升)注入距肛门括约肌7厘米处。6天或30天后,在连接到机械组织拉伸器的平板体外制备物中,从直肠神经干进行单单位细胞外记录。TNBS处理在6天时导致直肠黏膜出现肉眼可见的溃疡,到30天时完全愈合。肌肉收缩力不受TNBS处理的影响。处理后6天,低阈值直肠机械感受器对圆周拉伸的反应增强,在TNBS处理的组织中,用von Frey毛发阈值≤0.1毫牛做出反应的传入神经比例以及对电刺激的机械感受器兴奋性均增加,这表明机械转导器的敏感性增加。处理后30天时机械感受器功能在大多数情况下未发生变化。炎症介质前列腺素E2(1微摩尔)在伴有收缩活动的情况下激活机械感受器(6天),但辣椒素(1微摩尔)未能激活机械感受器。缓激肽(B1微摩尔)独立于收缩活动激活机械感受器,并且在存在缓激肽的情况下对拉伸的反应增强。辣椒素和缓激肽均独立于收缩活动激活未明确的拉伸不敏感传入神经。处理后6天时机械感受器功能受到调节,但30天时未受调节,这表明炎症组织中机械感受器敏感性适度增加,但恢复后则不然。其他未分类的确拉伸不敏感传入神经对炎症介质和辣椒素产生反应,可能参与内脏感觉的某些方面。