Sexual dimorphism in the contribution of neuroendocrine stress axes to oxaliplatin-induced painful peripheral neuropathy.
Sexual dimorphism in the contribution of neuroendocrine stress axes to oxaliplatin-induced painful peripheral neuropathy.
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神经内分泌应激轴在奥沙利铂诱导的痛性周围神经病中的性别二态作用。
DOI：
10.1097/j.pain.0000000000002073
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发表时间：
2021-03-01
期刊：
影响因子：
7.4
通讯作者：
Levine JD
中科院分区：
文献类型：
--
作者：
Staurengo-Ferrari L;Green PG;Araldi D;Ferrari LF;Miaskowski C;Levine JD
虽然临床研究支持压力是疼痛性化疗诱导的周围神经病变（CIPN）的危险因素，但几乎没有科学验证支持这种联系。在这里，我们评估了应激对奥沙利铂诱导的雄性和雌性大鼠CIPN的影响及其潜在机制。奥沙利铂单次给药在两种性别动物中产生了相似程度的机械性痛觉过敏，在第28天两种性别动物中仍然存在相似程度的机械性痛觉过敏。肾上腺切除术缓解了两种性别中奥沙利铂诱导的痛觉过敏。为了证实神经内分泌应激轴在CIPN中的作用，鞘内给予靶向B β-肾上腺素能受体mRNA的反义寡核苷酸可预防和逆转奥沙利铂诱导的痛觉过敏，仅在雄性动物中。相比之下，糖皮质激素受体反义寡核苷酸预防和逆转奥沙利铂诱导的痛觉过敏的两种性别。不可预测的声音应力增强CIPN，在两种性别。管理的压力激素，肾上腺素，皮质酮，以及它们的组合，在压力水平，模仿声音压力对CIPN的影响，在男性。在女性中，只有皮质酮模仿声音压力的影响。此外，CIPN的风险因素，早期生活压力，通过在成人中产生压力敏感（由新生儿有限的寝具产生）和压力弹性（由新生儿处理产生）表型进行评估。虽然新生儿有限的床上用品显着增强CIPN只在女性成年人，新生儿处理显着衰减CIPN，在两种性别。我们的研究表明，在奥沙利铂诱导的神经病理性疼痛中，2个主要神经内分泌应激轴的性别二态性作用。
Although clinical studies support the suggestion that stress is a risk factor for painful chemotherapy-induced peripheral neuropathy (CIPN), there is little scientific validation to support this link. Here, we evaluated the impact of stress on CIPN induced by oxaliplatin, and its underlying mechanisms, in male and female rats. A single dose of oxaliplatin produced mechanical hyperalgesia of similar magnitude in both sexes, still present at similar magnitude in both sexes, on day 28. Adrenalectomy mitigated oxaliplatin-induced hyperalgesia, in both sexes. To confirm the role of neuroendocrine stress axes in CIPN, intrathecal administration of antisense oligodeoxynucleotide targeting b₂-adrenergic receptor mRNA both prevented and reversed oxaliplatin-induced hyperalgesia, only in males. By contrast, glucocorticoid receptor antisense oligodeoxynucleotide prevented and reversed oxaliplatin-induced hyperalgesia in both sexes. Unpredictable sound stress enhanced CIPN, in both sexes. The administration of stress hormones, epinephrine, corticosterone, and their combination, at stress levels, mimicked the effects of sound stress on CIPN, in males. In females, only corticosterone mimicked the effect of sound stress. Also, a risk factor for CIPN, early-life stress, was evaluated by producing both stress-sensitive (produced by neonatal limited bedding) and stress-resilient (produced by neonatal handling) phenotypes in adults. Although neonatal limited bedding significantly enhanced CIPN only in female adults, neonatal handling significantly attenuated CIPN, in both sexes. Our study demonstrates a sexually dimorphic role of the 2 major neuroendocrine stress axes in oxaliplatin-induced neuropathic pain.
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影响因子：
4
作者：
Alvarez, Pedro;Green, Paul G.;Levine, Jon D.
通讯作者：
Levine, Jon D.
影响因子：
4.8
作者：
Daskalakis NP;De Kloet ER;Yehuda R;Malaspina D;Kranz TM
通讯作者：
Kranz TM
DOI：
10.1016/j.ijdevneu.2015.09.010
发表时间：
2015-12-01
影响因子：
1.8
作者：
Freitas, Daniele;Antoniazzi, Caren T. D.;Burger, Marilise Escobar
通讯作者：
Burger, Marilise Escobar
影响因子：
3.4
作者：
Dina, OA;Aley, KO;Levine, JD
通讯作者：
Levine, JD
DOI：
10.1016/s2215-0366(17)30014-7
发表时间：
2017-04
期刊：
The lancet. Psychiatry
影响因子：
--
作者：
Cordova MJ;Riba MB;Spiegel D
通讯作者：
Spiegel D