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6-OHDA 诱导的黑质纹状体通路单侧病变引起的痛觉过敏和痛觉过度被普拉克索逆转。

Unilateral lesion of the nigroestriatal pathway with 6-OHDA induced allodynia and hyperalgesia reverted by pramipexol in rats.

机构信息

Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Xochimilco, Calzada del Hueso 1100, Colonia Villa Quietud, 04960, México, D.F., Mexico.

Laboratorio de Neuroquímica, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico.

出版信息

Eur J Pharmacol. 2020 Feb 15;869:172814. doi: 10.1016/j.ejphar.2019.172814. Epub 2019 Nov 18.

Abstract

Pain is the non-motor symptom with the highest prevalence in patients with Parkinson's Disease (PD) affecting 40-85%. This study aimed to investigate the development of tactile allodynia and mechanical hyperalgesia after the nigrostriatal dopaminergic lesion induced by the unilateral 6-hydroxydopamine (6-OHDA) injection at different doses in the substantia nigra pars compacta (SNpc). Moreover, we studied the possible antiallodynic and antihyperalgesic effect with the acute and the subacute treatment of the pramipexole (PPX) in rats. First, dopaminergic lesion was realized by the unilateral injection of 6-OHDA (6, 10 and 16 μg/μl) into the SNpc. To know the establishment of motor deficits, we measure several turns and forelimb-use asymmetry by rotational behavior and cylinder, respectively. On the other hand, to investigate allodynia and hyperalgesia induced by 6-OHDA, we used the von Frey filaments. Moreover, antiallodynic and antihyperalgesic effect induced by PPX (0.03, 0.3 and 3 mg/kg, s.c.) was examined on acute and subacute conditions. We found that major dopaminergic lesion with 16 μg/μl of 6-OHDA caused the highest allodynia and hyperalgesia effects in both paws, as well as the major motor deficits. In addition, the treatment with PPX at 0.3 mg/kg reverts the allodynia and the hyperalgesia induced by 6-OHDA. In conclusion, the dopaminergic lesion into SNpc induce allodynia and hyperalgesia in both paws; interestingly the treatment with PPX can be suggested as an analgesic drug for patients with PD.

摘要

疼痛是帕金森病(PD)患者中发病率最高的非运动症状,影响 40-85%的患者。本研究旨在探讨单侧 6-羟多巴胺(6-OHDA)注射到黑质致密部(SNpc)不同剂量后引起黑质纹状体多巴胺能损伤后触觉性痛觉过敏和机械性痛觉过敏的发展。此外,我们研究了普拉克索(PPX)在大鼠中的急性和亚急性治疗对痛觉过敏和痛觉过敏的可能抗作用。首先,通过单侧注射 6-OHDA(6、10 和 16μg/μl)到 SNpc 来实现多巴胺能损伤。为了了解运动缺陷的建立,我们通过旋转行为和圆柱分别测量几个转弯和前肢使用的不对称性。另一方面,为了研究 6-OHDA 引起的痛觉过敏和痛觉过敏,我们使用了冯弗雷尔细丝。此外,还研究了 PPX(0.03、0.3 和 3mg/kg,皮下注射)在急性和亚急性条件下引起的抗痛觉过敏和抗痛觉过敏作用。我们发现,用 16μg/μl 的 6-OHDA 引起的主要多巴胺能损伤导致了两爪的最大痛觉过敏和痛觉过敏效应,以及最大的运动缺陷。此外,用 0.3mg/kg 的 PPX 治疗可以逆转 6-OHDA 引起的痛觉过敏和痛觉过敏。总之,SNpc 中的多巴胺能损伤会引起两爪的痛觉过敏和痛觉过敏;有趣的是,PPX 的治疗可以被建议为 PD 患者的一种镇痛药物。

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