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牙髓和导水管周围灰质电刺激对大鼠脑室灌流液中β-内啡肽释放的影响。

Effect of tooth pulp and periaqueductal central gray electrical stimulation on β-endorphin release into the fluid perfusing the cerebral ventricles in rats.

机构信息

Department of Experimental Physiology, Medical University, Lodz, Poland.

出版信息

Brain Res. 2011 Aug 8;1405:15-22. doi: 10.1016/j.brainres.2011.06.030. Epub 2011 Jul 8.

Abstract

Our previous studies demonstrated that tooth pulp stimulation increases the pain threshold, whereas stimulation of the periaqueductal central gray (PAG) has the opposite effect. The aim of this study was to investigate the effect exerted by electrical stimulation of the nociceptive afferent terminals in the tooth pulp and analgesic electrical stimulation of the PAG on the release of immunoreactive β-endorphin (β-EP-IR) into the cerebrospinal fluid (CSF) and artificial cerebrospinal fluid (aCSF) perfusing the cerebral ventricles in rat, and to establish whether during such stimulation the μ-opioid receptor (MOR) was activated. The tongue jerk reflex was induced by dental pulp stimulation in rats under chloralose anesthesia. CSF was collected from the cerebello-medullary cistern, and then 30-minute perfusions of the lateral ventricles with aCSF were conducted with collection of perfusate portions from the cerebello-medullary cistern at rest (control), during electrical tooth pulp stimulation evoking the nociceptive tongue jerk reflex and during inhibition of that reflex with simultaneous stimulation of tooth pulp and the PAG. In the second series of experiments, a MOR-selective antagonist, β-funaltrexamine (β-FNA) was perfused through the cerebral ventricles 10min before tooth pulp stimulation. β-EP-IR was determined in the collected CSF and aCSF perfusates by radioimmunoassay (RIA). Stimulation of tooth pulp with electrical impulses resulted in a significant increase of β-EP-IR. On the other hand, simultaneous tooth pulp and PAG stimulation inhibited β-EP-IR release into the fluid perfusing the cerebral ventricles. β-FNA blocked evoked tongue jerks (ETJ) induced by PAG stimulation, but no enhancing effect of β-FNA on β-EP-IR release into the perfusate was observed. The obtained results indicate that stimulation of the tooth pulp increases β-EP release significantly, whereas PAG stimulation significantly inhibits β-EP-IR release into the CSF, and that these effects are mediated by MOR. The results of the experiments allow to conclude that endogenous β-EP, released as a result of electrical tooth pulp stimulation in orofacial pain, diffuses through the cerebroventricular ependyma into the CSF and exerts a modulatory effect, mediated by MOR, alterating the properties of neurons in the trigeminal sensory nuclei, interneurons, and motoneurons of the hypoglossal nerve.

摘要

我们之前的研究表明,牙髓刺激会提高疼痛阈值,而导水管周围灰质(periaqueductal central gray,PAG)的刺激则会产生相反的效果。本研究旨在探讨牙髓伤害性传入末梢的电刺激和 PAG 的镇痛电刺激对大鼠脑室灌流脑脊液(cerebrospinal fluid,CSF)和人工脑脊液(artificial cerebrospinal fluid,aCSF)中免疫反应β-内啡肽(β-endorphin,β-EP-IR)释放的影响,并确定在这种刺激下,μ-阿片受体(μ-opioid receptor,MOR)是否被激活。在氯醛糖麻醉下,通过牙髓刺激诱导大鼠的舌反射。从小脑延髓池收集 CSF,然后用 aCSF 对侧脑室进行 30 分钟灌流,在休息时(对照)、电刺激牙髓引起疼痛性舌反射时以及同时刺激牙髓和 PAG 抑制该反射时,从小脑延髓池收集灌流部分。在第二组实验中,在牙髓刺激前 10 分钟通过脑室灌流给予 MOR 选择性拮抗剂β-正丁啡烷(β-funaltrexamine,β-FNA)。通过放射免疫分析(radioimmunoassay,RIA)测定收集的 CSF 和 aCSF 灌流液中的β-EP-IR。电刺激牙髓会显著增加β-EP-IR。另一方面,同时刺激牙髓和 PAG 会抑制β-EP-IR 释放到灌流到脑室的液体中。β-FNA 阻断了 PAG 刺激引起的诱发舌反射(evoked tongue jerks,ETJ),但没有观察到β-FNA 对灌流液中β-EP-IR 释放的增强作用。研究结果表明,牙髓刺激会显著增加β-EP 的释放,而 PAG 刺激会显著抑制β-EP-IR 释放到 CSF 中,这些效应是由 MOR 介导的。实验结果表明,内源性β-EP 是由口腔面部疼痛的电刺激牙髓释放的,它通过脑室室管膜扩散到 CSF 中,并通过 MOR 介导,改变三叉神经感觉核、中间神经元和舌下神经运动神经元的神经元特性,从而发挥调节作用。

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