Laboratório de Farmacologia da Dor e Neuromodulação, Investigações Pré-clínicas, Centro de Pesquisa Experimental (CPE), Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-007, Brazil.
Unidade de Experimentação Animal, Grupo de Pesquisa e Pós-Graduação, HCPA, Porto Alegre, RS, Brazil.
Purinergic Signal. 2020 Dec;16(4):573-584. doi: 10.1007/s11302-020-09751-w. Epub 2020 Nov 8.
This study aimed to evaluate the effect of a single administration of IB-MECA, an A3 adenosine receptor agonist, upon the nociceptive response and central biomarkers of rats submitted to chronic pain models. A total of 136 adult male Wistar rats were divided into two protocols: (1) chronic inflammatory pain (CIP) using complete Freund's adjuvant and (2) neuropathic pain (NP) by chronic constriction injury of the sciatic nerve. Thermal and mechanical hyperalgesia was measured using von Frey (VF), Randal-Selitto (RS), and hot plate (HP) tests. Rats were treated with a single dose of IB-MECA (0.5 μmol/kg i.p.), a vehicle (dimethyl sulfoxide-DMSO), or positive control (morphine, 5 mg/kg i.p.). Interleukin 1β (IL-1β), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) levels were measured in the brainstem and spinal cord using enzyme-linked immunosorbent assay (ELISA). The establishment of the chronic pain (CIP or NP) model was observed 14 days after induction by a decreased nociceptive threshold in all three tests (GEE, P < 0.05). The antinociceptive effect of a single dose of IB-MECA was observed in both chronic pain models, but this was more effective in NP model. There was an increase in IL-1β levels promoted by CIP. NP model promoted increase in the brainstem BDNF levels, which was reversed by IB-MECA.
本研究旨在评估单次给予 A3 腺苷受体激动剂 IB-MECA 对慢性疼痛模型大鼠的痛觉反应和中枢生物标志物的影响。共有 136 只成年雄性 Wistar 大鼠分为两个方案：（1）使用完全弗氏佐剂的慢性炎症性疼痛（CIP），（2）通过坐骨神经慢性缩窄性损伤的神经病理性疼痛（NP）。使用 von Frey（VF）、Randal-Selitto（RS）和热板（HP）测试测量热和机械性痛觉过敏。大鼠用单剂量 IB-MECA（0.5μmol/kg ip）、载体（二甲亚砜-DMSO）或阳性对照（吗啡，5mg/kg ip）处理。使用酶联免疫吸附测定（ELISA）测量脑干和脊髓中的白细胞介素 1β（IL-1β）、脑源性神经营养因子（BDNF）和神经生长因子（NGF）水平。在诱导后 14 天，通过三种测试中的痛觉阈值降低观察到慢性疼痛（CIP 或 NP）模型的建立（广义估计方程，P<0.05）。单次给予 IB-MECA 的镇痛作用在两种慢性疼痛模型中均观察到，但在 NP 模型中更为有效。CIP 促进了 IL-1β 水平的增加。NP 模型促进了脑干 BDNF 水平的增加，IB-MECA 逆转了这一增加。
