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The Buspirone-dependent Abdominal Pain Transmission Within the Nucleus Tractus Solitarius in the Rat
Neuroscience ( IF 3.3 ) Pub Date : 2020-11-26 , DOI: 10.1016/j.neuroscience.2020.11.032
Sergey S. Panteleev , Ivan B. Sivachenko , Olga A. Lyubashina

Buspirone, a partial agonist of the 5-HT1aR, due to potential antinociceptive properties can be useful for abdominal pain treatment in IBS patients. Pain-related effects of buspirone can be mediated by the 5-HT1aRs, located within the nucleus tractus solitarius. The 5-HT1aR involvement in pain transmission within the NTS is unclear. The objective of our study was to evaluate the involvement of the 5-HT1aR in abdominal pain transmission within the NTS. Using a model of abdominal pain on urethane-anesthetized rats, two types of NTS pain-related neurons responding to the noxious colorectal distension (CRD) with excitatory and inhibitory sustained patterns of evoked activity were revealed. Buspirone (1.0–4.0 mg kg−1, iv) has complex time- and dose-depended action on the CRD-induced NTS neuron responses. Buspirone inhibits the responses of the excitatory neurons and inverts the responses of the inhibitory pain-related neurons but at a dose of 4.0 buspirone, the effect on NTS pain-related neurons attenuates. The inhibitory effect of buspirone on the CRD-evoked responses of the excitatory NTS neurons is completely blocked by an intra-cerebroventricular administration of buspirone agonist WAY100,635. The inhibitory responses do not change by this agonist. The inhibitory action of buspirone is mediated by supraspinal 5-HT1a receptors however, its excitatory effect on inhibitory neurons does not dependents on these receptors. We proposed that the NTS pain-related neurons could be involved in anti- or pronociceptive effects of buspirone on abdominal pain.



中文翻译:

大鼠孤束核内丁螺环酮依赖性腹痛的传递

由于潜在的抗伤害感受特性,丁螺环酮是5-HT 1a R的部分激动剂,可用于IBS患者的腹痛治疗。丁螺环酮的疼痛相关效应可以由位于孤束核内的5-HT 1a Rs介导。5-HT 1a R是否参与NTS内的疼痛传递尚不清楚。我们研究的目的是评估5-HT 1a R在NTS内腹痛传播中的作用。使用在氨基甲酸乙酯麻醉的大鼠上的腹痛模型,揭示了两种类型的NTS痛相关神经元,它们对有害的结直肠扩张(CRD)有兴奋性和抑制性的持续活动。丁螺环酮(1.0–4.0 mg千克-1,iv)对CRD诱导的NTS神经元反应具有复杂的时间和剂量依赖性作用。丁螺环酮抑制兴奋性神经元的反应并反转抑制性疼痛相关神经元的反应,但丁螺环酮的剂量为4.0时,对NTS疼痛相关神经元的作用减弱。丁螺环酮对脑室内施用丁螺环酮激动剂WAY100,635完全阻断了丁螺环酮对CRD诱发的NTS神经元兴奋反应的抑制作用。该激动剂不会改变抑制反应。丁螺环酮的抑制作用由脊髓上5-HT 1a介导然而,其对抑制性神经元的兴奋作用并不依赖于这些受体。我们建议NTS疼痛相关的神经元可能参与丁螺环酮对腹痛的抗或镇痛作用。

更新日期:2020-12-09
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