Severity of alcohol-induced painful peripheral neuropathy in female rats:: Role of estrogen and protein kinase (A and Cε)
Severity of alcohol-induced painful peripheral neuropathy in female rats:: Role of estrogen and protein kinase (A and Cε)
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DOI：
10.1016/j.neuroscience.2006.11.053
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发表时间：
2007-03-02
期刊：
影响因子：
3.3
通讯作者：
Levine, J. D.
中科院分区：
文献类型：
--
作者：
Dina, O. A.;Gear, R. W.;Levine, J. D.
小纤维痛性周围神经病是慢性酒精摄入的并发症，在女性中更为严重。在目前的研究中，我们在大鼠身上复制了这一临床发现，并评估了雌激素和第二信使信号通路的作用。酒精饮食(6.5%酒精体积：Lieber-DeCarli公式中的体积)在女性中引起痛敏，起病更快，程度更严重。摘除卵巢后，酒精未能在雌性大鼠中引起痛觉过敏，远远超过了性腺完整的雄性和雌性大鼠的发病时间。雌激素替代恢复雌性大鼠酒精性神经病。蛋白激酶A(PKA)抑制剂(Walsh抑制肽，WIPTIDE)仅能减轻乙醇诱导的雌性大鼠的痛敏。2‘-氨基-3’-甲氧基黄酮类(PD98059)和1，4-二氨基-2，3-二氰基-1，4-二(2-氨基苯硫基)丁二烯(UO126)等蛋白激酶C epsilon-I和ERK 1/2(2‘-氨基-3’-甲氧基黄酮(PD98059)和1，4-二氨基-2，3-二氰基-1，4-二(2-氨基苯硫基)丁二烯(UO126))的抑制剂可减轻雄性和雌性大鼠的痛敏反应，但PKC epsilon-I对雌性大鼠痛敏反应的抑制程度要大得多。总之，雌激素在雌性大鼠酒精性神经病相关疼痛的表达中起着重要作用。在炎症性痛觉过敏中，只有PKC epsilon信号的作用是性二态的，而在酒精神经病中，PKA和PKC epsilon信号是高度性二态的。(C)2006年IBRO。爱思唯尔有限公司出版。保留所有权利。
Small-fiber painful peripheral neuropathy, a complication of chronic ethanol ingestion, is more severe in women. In the present study, we have replicated this clinical finding in the rat and evaluated for a role of estrogen and second messenger signaling pathways. The alcohol diet (6.5% ethanol volume:volume in Lieber-DeCarli formula) induced hyperalgesia with more rapid onset and severity in females. Following ovariectomy, alcohol failed to induce hyperalgesia in female rats, well past its time to onset in gonad intact males and females. Estrogen replacement reinstated alcohol neuropathy in the female rat. The protein kinase A (PKA) inhibitor (Walsh inhibitor peptide, WIPTIDE) only attenuated alcohol-induced hyperalgesia in female rats. Inhibitors of protein kinase C epsilon, (PKC epsilon-I) and extracellular-signal related kinase (ERK) 1/2 (2'-amino-3'-methoxyflavone (PD98059) and 1,4-diamino-2, 3-dicyano-1, 4-bis (2-aminophenylthio) butadiene (UO126)) attenuated hyperalgesia in males and females, however the degree of attenuation produced by PKC epsilon-I was much greater in females. In conclusion, estrogen plays an important role in the expression of pain associated with alcohol neuropathy in the female rat. In contrast to inflammatory hyperalgesia, in which only the contribution of PKC epsilon signaling is sexually dimorphic, in alcohol neuropathy PKA as well as PKC epsilon signaling is highly sexually dimorphic. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.