Behavioral and inflammatory sex differences revealed by celecoxib nanotherapeutic treatment of peripheral neuroinflammation.
Behavioral and inflammatory sex differences revealed by celecoxib nanotherapeutic treatment of peripheral neuroinflammation.
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DOI：
10.1038/s41598-022-12248-8
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发表时间：
2022-05-30
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
神经性疼痛影响着全世界数百万人，但其发展和持续的分子机制却知之甚少。鉴于男性历来被用作临床前研究的主要性别，对女性神经炎症对损伤的反应、疼痛的形成或对缓解疼痛治疗的反应知之甚少。巨噬细胞通过其环氧合酶-2（考克斯-2）酶的活化导致前列腺素E2（PGE 2）的产生而促进神经炎性疼痛的发展。PGE 2激活伤害感受并影响额外的白细胞浸润。考克斯-2活性的减弱可降低炎性疼痛，最常见的是通过非甾体抗炎药（NSAID）实现，但由于脱靶毒性，NSAID被认为对神经性疼痛无效。使用大鼠坐骨神经的慢性压迫损伤，我们表明，男性和女性表现出定量相同程度的机械性异常性疼痛损伤后。此外，含有NSAID塞来昔布的低剂量纳米粒被循环单核细胞吞噬，然后在损伤部位自然积聚为巨噬细胞。使用这种纳米粒子，我们表明，治疗的男性表现出完全逆转的超敏反应，而相同剂量的纳米粒子在女性提供了一个衰减的救济。对纳米疗法的行为反应的差异反映在损伤部位浸润性巨噬细胞的减少上。本研究中的观察结果强化了女性神经炎症与男性不同的概念。
Neuropathic pain affects millions of people worldwide, yet the molecular mechanisms of how it develops and persists are poorly understood. Given that males have historically been utilized as the primary sex in preclinical studies, less is known about the female neuroinflammatory response to injury, formation of pain, or response to pain-relieving therapies. Macrophages contribute to the development of neuroinflammatory pain via the activation of their cyclooxygenase-2 (COX-2) enzyme, which leads to the production of prostaglandin E2 (PGE2). PGE2 activates nociception and influences additional leukocyte infiltration. Attenuation of COX-2 activity decreases inflammatory pain, most commonly achieved by nonsteroidal anti-inflammatory drugs (NSAIDs), yet NSAIDs are considered ineffective for neuropathic pain due to off target toxicity. Using chronic constriction injury of the rat sciatic nerve, we show that males and females exhibit quantitatively the same degree of mechanical allodynia post injury. Furthermore, a low-dose nanotherapeutic containing the NSAID celecoxib is phagocytosed by circulating monocytes that then naturally accumulate at sites of injury as macrophages. Using this nanotherapeutic, we show that treated males exhibit complete reversal of hypersensitivity, while the same dose of nanotherapeutic in females provides an attenuated relief. The difference in behavioral response to the nanotherapy is reflected in the reduction of infiltrating macrophages at the site of injury. The observations contained in this study reinforce the notion that female neuroinflammation is different than males.
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影响因子：
7.8
作者：
Giefing-Kröll C;Berger P;Lepperdinger G;Grubeck-Loebenstein B
通讯作者：
Grubeck-Loebenstein B
影响因子：
3.3
作者：
Janjic JM;Vasudeva K;Saleem M;Stevens A;Liu L;Patel S;Pollock JA
通讯作者：
Pollock JA
影响因子：
9.3
作者：
González H;Pacheco R
通讯作者：
Pacheco R
影响因子：
1.6
作者：
Craft RM;Hewitt KA;Britch SC
通讯作者：
Britch SC
影响因子：
2.5
作者：
Lopshire, JC;Nicol, GD
通讯作者：
Nicol, GD