Acetaminophen and pregabalin attenuate central sensitization in rodent models of nociplastic widespread pain
Acetaminophen and pregabalin attenuate central sensitization in rodent models of nociplastic widespread pain
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对乙酰氨基酚和普瑞巴林减弱啮齿动物模型中伤害性广泛疼痛的中枢敏化
DOI：
10.1016/j.neuropharm.2022.109029
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发表时间：
2022
影响因子：
4.7
通讯作者：
Fusao Kato
中科院分区：
文献类型：
--
作者：
Manami Yajima;Mariko Sugimoto;Yae K.Sugimura;Yukari Takahashi;Fusao Kato
“伤害性疼痛”是最近提出的一种新的机制性疼痛描述词，其定义为通过改变伤害性感受而发生的疼痛，而没有伤害性感受器激活和神经损伤。伤害性疼痛通常以多个身体区域中的广泛疼痛敏感化（WSP）为特征（Fitzcharles等人，2021年）。由于许多原发性慢性疼痛患者都有伤害性疼痛背景，因此迫切需要开发适当的方法来评估动物模型中药物对伤害性疼痛的作用。使用两种WSP大鼠模型，其涉及通过口面炎症或直接化学发生激活的中央杏仁核（CeA）激活（Sugimoto等人，2021），我们检查了广泛使用的镇痛药，对乙酰氨基酚（AcAph），普瑞巴林（PGB）和度洛沙汀（DLX）是否可以减轻WSP。AcAph（100或200 mg/kg，i.p.）显著提高了50%缩爪阈值（PWT 50），该阈值在具有在右侧CeA中表达的兴奋性设计受体（hM 3Dq）的大鼠中通过上唇注射福尔马林或全身注射氯氮平-N-氧化物而显著降低。此作用持续时间> 104 h。PGB（30 mg/kg，i.p.）对口面部注射福尔马林> 1.6h大鼠PWT_（50）的降低也有明显的对抗作用。DLX对WSP无效。基于这些结果，我们建议这些临床前模型可用于评估原发性慢性疼痛的药物作用。我们的结论是，广泛使用的止痛药，AcAph和PGB，也减轻伤害性广泛敏化的情况下，正在进行的伤害感受器激活和神经injure.This文章的一部分，在“进展机制和治疗目标有关的疼痛”的特刊。
The “nociplastic pain,” a recently proposed novel mechanistic pain descriptor, is defined as pain occurring through altered nociception without nociceptor activation and nerve injury. Nociplastic pain is often characterized by widespread pain sensitization (WSP) in multiple body regions (Fitzcharles et al., 2021). As many patients with primary chronic pain would have nociplastic backgrounds, developing appropriate methods to evaluate drug effects against nociplastic pain in animal model is in great demand. Using two rat models with the WSP involving central amygdala (CeA) activation by orofacial inflammation or direct chemogenetic activation (Sugimoto et al., 2021), we examined whether widely used analgesics, acetaminophen (AcAph), pregabalin (PGB), and duloxetine (DLX) could attenuate the WSP. AcAph (100 or 200 mg/kg, i.p.) significantly elevated 50%-paw withdrawal threshold (PWT50), which had been lowered significantly by upper lip injection of formalin, or systemic injection of clozapine-N-oxide in the rats with excitatory designer receptors (hM3Dq) expressed in the right CeA. This effect lasted for > ∼4 h. PGB (30 mg/kg, i.p.) also significantly counteracted the lowered PWT50in rats with orofacial formalin injection for >∼6 h. DLX was ineffective on the WSP. Based on these results, we propose that these preclinical models could be used to evaluate drug effects for primary chronic pain. We conclude that the widely used pain killers, AcAph and PGB, also relieve nociplastic widespread sensitization in the absence of ongoing nociceptor activation and nerve injury.This article is part of the Special Issue on ‘Advances in mechanisms and therapeutic targets relevant to pain’.
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影响因子：
5
作者：
Munro, Gordon
通讯作者：
Munro, Gordon
疼痛敏化
DOI：
10.1201/9780429288210-71
发表时间：
2020
期刊：
Principles of Physiology for the Anaesthetist
影响因子：
--
作者：
P. Kam;I. Power;M. Cousins;Philip J. Siddal
通讯作者：
Philip J. Siddal
周围神经损伤对大鼠蓝斑神经元反应特性及蓝脊髓镇痛的影响
影响因子：
3.3
作者：
H. Viisanen;A. Pertovaara
通讯作者：
A. Pertovaara
影响因子：
4
作者：
Greenspan, Joel D.;Slade, Gary D.;Bair, Eric;Dubner, Ronald;Fillingim, Roger B.;Ohrbach, Richard;Knott, Charles;Diatchenko, Luda;Liu, Qian;Maixner, William
通讯作者：
Maixner, William
DOI：
10.1016/j.ynpai.2021.100078
发表时间：
2021-08
期刊：
Neurobiology of pain (Cambridge, Mass.)
影响因子：
--
作者：
Yamamoto S;Takahashi Y;Kato F
通讯作者：
Kato F