Characterization of the Dahl salt-sensitive rat as a rodent model of inherited, widespread, persistent pain.
Characterization of the Dahl salt-sensitive rat as a rodent model of inherited, widespread, persistent pain.
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Dahl盐敏感大鼠的表征是遗传，广泛，持续性疼痛的啮齿动物模型。
DOI：
10.1038/s41598-022-24094-9
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发表时间：
2022-11-11
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
动物模型对于研究慢性疼痛障碍的病理生理学和作为新疗法的筛选工具是必不可少的。然而，现有的大多数模型都不能再现临床持续性疼痛的关键特征。这限制了他们准确预测哪些新药将在临床上有效的能力。在这里，我们将Dahl盐敏感(SS)大鼠品系描述为第一个遗传性广泛性痛觉过敏的啮齿动物模型。我们发现，这种菌株表现出与慢性疼痛有关的生理表型，如神经炎症、内源性疼痛调制缺陷、下丘脑-垂体-肾上腺轴功能障碍、氧化应激增加和免疫细胞激活。与SpragueDawley和Brown挪威大鼠相比，SS大鼠由于炎性介质浓度增加、皮质酮水平降低和高氧化应激而具有较低的伤害性阈值。地塞米松、活性氧清除剂坦普尔或胶质细胞抑制剂米诺环素可降低SS大鼠的疼痛敏感性，而不影响其他菌株，而吲哚美辛和加巴喷丁的止痛效果较差。此外，SS大鼠表现出弥散伤害性抑制控制受损，对前痛介质PGE2的反应加剧，这是全身性疼痛条件的特征。这些数据建立了这种菌株作为一种新的自发的、广泛的痛敏模型，可以用来识别慢性疼痛诊断和治疗的生物标记物。
Animal models are essential for studying the pathophysiology of chronic pain disorders and as screening tools for new therapies. However, most models available do not reproduce key characteristics of clinical persistent pain. This has limited their ability to accurately predict which new medicines will be clinically effective. Here, we characterize the Dahl salt-sensitive (SS) rat strain as the first rodent model of inherited widespread hyperalgesia. We show that this strain exhibits physiological phenotypes known to contribute to chronic pain, such as neuroinflammation, defective endogenous pain modulation, dysfunctional hypothalamic–pituitary–adrenal axis, increased oxidative stress and immune cell activation. When compared with Sprague Dawley and Brown Norway rats, SS rats have lower nociceptive thresholds due to increased inflammatory mediator concentrations, lower corticosterone levels, and high oxidative stress. Treatment with dexamethasone, the reactive oxygen species scavenger tempol, or the glial inhibitor minocycline attenuated the pain sensitivity in SS rats without affecting the other strains while indomethacin and gabapentin provided less robust pain relief. Moreover, SS rats presented impaired diffuse noxious inhibitory controls and an exacerbated response to the proalgesic mediator PGE2, features of generalized pain conditions. These data establish this strain as a novel model of spontaneous, widespread hyperalgesia that can be used to identify biomarkers for chronic pain diagnosis and treatment.
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DOI：
10.1161/hypertensionaha.113.01194
发表时间：
2013-07
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Cowley AW Jr;Ryan RP;Kurth T;Skelton MM;Schock-Kusch D;Gretz N
通讯作者：
Gretz N
影响因子：
9.3
作者：
Dansereau MA;Midavaine É;Bégin-Lavallée V;Belkouch M;Beaudet N;Longpré JM;Mélik-Parsadaniantz S;Sarret P
通讯作者：
Sarret P
影响因子：
29
作者：
Feng D;Yang C;Geurts AM;Kurth T;Liang M;Lazar J;Mattson DL;O'Connor PM;Cowley AW Jr
通讯作者：
Cowley AW Jr
影响因子：
4.6
作者：
Cowley, AW;Stoll, M;Jacob, HJ
通讯作者：
Jacob, HJ
DOI：
10.4088/pcc.08m00680
发表时间：
2009-01-01
期刊：
Primary care companion to the Journal of clinical psychiatry
影响因子：
--
作者：
Arnold, Lesley M;Clauw, Daniel J;Chappell, Amy S
通讯作者：
Chappell, Amy S