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鞘内注射催产素可改善大鼠术后疼痛模型的自发行为并减轻机械性超敏反应。

Intrathecal Oxytocin Improves Spontaneous Behavior and Reduces Mechanical Hypersensitivity in a Rat Model of Postoperative Pain.

作者信息

Espinosa De Los Monteros-Zúñiga Antonio, Martínez-Lorenzana Guadalupe, Condés-Lara Miguel, González-Hernández Abimael

机构信息

Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Queretaro, Mexico.

出版信息

Front Pharmacol. 2020 Sep 16;11:581544. doi: 10.3389/fphar.2020.581544. eCollection 2020.

DOI:10.3389/fphar.2020.581544
PMID:33071793
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7533545/
Abstract

The first few days post-surgery, patients experience intense pain, hypersensitivity and consequently tend to have minor locomotor activity to avoid pain. Certainly, injury to peripheral tissues produces pain and increases sensitivity to painful (hyperalgesia) and non-painful (allodynia) stimuli. In this regard, preemptive pharmacological treatments to avoid or diminish pain after surgery are relevant. Recent data suggest that the neuropeptide oxytocin when given at spinal cord level could be a molecule with potential preemptive analgesic effects, but this hypothesis has not been properly tested. Using a validated postoperative pain model ( plantar incision), we evaluated in male Wistar rats the potential preemptive antinociceptive effects of intrathecal oxytocin administration measuring tactile hypersensitivity (across 8 days) and spontaneous motor activity (across 3 days). Hypersensitivity was evaluated using von Frey filaments, whereas spontaneous activity (total distance, vertical activity episodes, and time spent in the center of the box) was assessed in real time using a semiautomated open-field system. Under these conditions, we found that animals pretreated with spinal oxytocin before plantar incision showed a diminution of hypersensitivity and an improvement of spontaneous behavior (particularly total distance and vertical activity episodes). This report provides a basis for addressing the therapeutic relevance of oxytocin as a potential preemptive analgesic molecule.

摘要

术后的头几天,患者会经历剧烈疼痛、超敏反应,因此往往会减少运动活动以避免疼痛。当然,外周组织损伤会产生疼痛,并增加对疼痛性(痛觉过敏)和非疼痛性(感觉异常)刺激的敏感性。在这方面,避免或减轻术后疼痛的预防性药物治疗具有重要意义。最近的数据表明,在脊髓水平给予神经肽催产素可能是一种具有潜在预防性镇痛作用的分子,但这一假设尚未得到充分验证。我们使用经过验证的术后疼痛模型(足底切口),在雄性Wistar大鼠中评估鞘内注射催产素的潜在预防性抗伤害感受作用,测量触觉超敏反应(持续8天)和自发运动活动(持续3天)。使用von Frey细丝评估超敏反应,而使用半自动旷场系统实时评估自发活动(总距离、垂直活动次数和在箱体中心停留的时间)。在这些条件下,我们发现足底切口前接受脊髓催产素预处理的动物超敏反应减轻,自发行为得到改善(特别是总距离和垂直活动次数)。本报告为探讨催产素作为一种潜在的预防性镇痛分子的治疗相关性提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eea6/7533545/febe6e2f808b/fphar-11-581544-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eea6/7533545/cbf166fdef6a/fphar-11-581544-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eea6/7533545/ba5507336c9d/fphar-11-581544-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eea6/7533545/febe6e2f808b/fphar-11-581544-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eea6/7533545/cbf166fdef6a/fphar-11-581544-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eea6/7533545/ba5507336c9d/fphar-11-581544-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eea6/7533545/febe6e2f808b/fphar-11-581544-g003.jpg

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Oxytocin, GABA, and TRPV1, the Analgesic Triad?催产素、γ-氨基丁酸和瞬时受体电位香草酸亚型1,镇痛三联体?
Front Mol Neurosci. 2018 Nov 13;11:398. doi: 10.3389/fnmol.2018.00398. eCollection 2018.
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Anxiety Assessment in Pre-clinical Tests and in Clinical Trials: A Critical Review.
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