鞘内和全身给予巴氯芬均可产生大鼠膀胱抗伤害作用。

Systemic and intrathecal baclofen produce bladder antinociception in rats.

机构信息

Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, BMR2-208, 901 19th Street South, Birmingham, AL, 35294, USA.

Medtronics, Inc., Minneapolis, MN, USA.

出版信息

BMC Urol. 2021 Oct 4;21(1):139. doi: 10.1186/s12894-021-00899-0.

DOI:10.1186/s12894-021-00899-0

PMID:34607587

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8489106/

Abstract

BACKGROUND

Baclofen, a clinically available GABA receptor agonist, produces non-opioid analgesia in multiple models of pain but has not been tested for effects on bladder nociception.

METHODS

A series of experiments examined the effects of systemic and spinally administered baclofen on bladder nociception in female anesthetized rats. Models of bladder nociception included those which employed neonatal and adult bladder inflammation to produce bladder hypersensitivity.

RESULTS

Cumulative intraperitoneal dosing (1-8 mg/kg IP) and cumulative intrathecal dosing (10-160 ng IT) of baclofen led to dose-dependent inhibition of visceromotor responses (VMRs) to urinary bladder distension (UBD) in all tested models. There were no differences in the magnitude of the analgesic effects of baclofen as a function of inflammation versus no inflammation treatments. Hemodynamic (pressor) responses to UBD were similarly inhibited by IT baclofen as well as UBD-evoked excitatory responses of spinal dorsal horn neurons. The GABA receptor antagonist, CGP 35,348, antagonized the antinociceptive effects of IT baclofen on VMRs in all tested models but did not affect the magnitude of the VMRs by itself suggesting no tonic GABA activity was present in this preparation. Tolerance to a seven day continuous IT infusion of baclofen was not observed.

CONCLUSIONS

These data provide support for a clinical trial of baclofen as a non-opioid treatment of human bladder pain.

摘要

背景

巴氯芬是一种临床上可获得的 GABA 受体激动剂，在多种疼痛模型中产生非阿片类镇痛作用，但尚未测试其对膀胱痛觉的影响。

方法

一系列实验研究了系统给予和鞘内给予巴氯芬对麻醉雌性大鼠膀胱痛觉的影响。膀胱痛觉模型包括使用新生和成年膀胱炎症产生膀胱高敏性的模型。

结果

累积腹腔内给药（1-8mg/kg IP）和累积鞘内给药（10-160ng IT）巴氯芬导致所有测试模型中对尿囊扩张（UBD）的内脏运动反应（VMR）呈剂量依赖性抑制。巴氯芬的镇痛效果不因炎症与非炎症处理而有差异。脊髓背角神经元的 IT 巴氯芬和 UBD 诱发的兴奋性反应同样抑制 UBD 引起的血液动力学（升压）反应。GABA 受体拮抗剂 CGP 35348 拮抗 IT 巴氯芬对所有测试模型中 VMR 的抗伤害作用，但本身不影响 VMR 的幅度，表明在此制剂中不存在紧张性 GABA 活性。未观察到对巴氯芬连续七天 IT 输注的耐受性。