Estrogen effects on pain sensitivity and neuropeptide expression in rat sensory neurons.
Estrogen effects on pain sensitivity and neuropeptide expression in rat sensory neurons.
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DOI：
10.1016/j.expneurol.2010.03.006
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发表时间：
2010-07
影响因子：
5.3
通讯作者：
Oblinger, Monica M.
中科院分区：
文献类型：
--
作者：
Sarajari, Susan;Oblinger, Monica M.
关键词：
虽然许多慢性疼痛在女性中比男性更常见，但雌激素在调节伤害感受方面的作用仍不清楚。已知雌激素受体 (ER) 在伤害感受通路的各个部分表达，包括背根神经节 (DRG) 的小型初级感觉神经元。本研究评估了长期雌激素替代对雌性 Sprague Dawley 大鼠疼痛敏感性和 DRG 神经肽表达的影响。目的是评估雌激素是否以与其对疼痛敏感性的影响一致的方式调节 DRG 中的伤害性神经肽。我们的结果表明，与持续雌激素治疗的卵巢切除动物 (ovx+E) 相比，成年大鼠的长期（28 天）卵巢切除术 (ovx) 会引起后爪和尾部的深度热和机械痛觉过敏。使用免疫细胞化学和原位杂交 (ISH) 在含有 ER 的小腰椎 DRG 神经元中观察到两种神经肽 P 物质 (SP) 和降钙素基因相关肽 (CGRP) 表达的显着变化。雌激素对 CGRP 和 SP 的调节存在差异，在雌激素处理的动物的 DRG 中，SP 在肽和 mRNA 水平上均显着下调，而 CGRP 及其 mRNA 则增加。我们还评估了部分坐骨神经损伤后机械性异常性疼痛的发展，发现 ovx 和 ovx+E 动物在部分神经损伤后一周内出现明显的异常性疼痛，并持续至少一个月。经过雌激素治疗的动物在受伤后两周表现出异常疼痛程度的部分改善。总体而言，结果表明雌激素具有显着的抗伤害作用，该作用可能与 DRG 表达伤害性 ERα 的小神经元中两种肽表达的变化直接相关。
While a number of chronic pain conditions are much more prevalent in women than men, the role of estrogen in regulating nociception remains unclear. Estrogen receptors (ER) are known to be expressed in various parts of the nociceptive pathway, including in the small-sized primary sensory neurons of the dorsal root ganglion (DRG). This study evaluated the effects of long-term estrogen replacement on pain sensitivity and neuropeptide expression in the DRG of female Sprague Dawley rats. The goal was to evaluate whether estrogen modulates nociceptive neuropeptides in the DRG in a manner consistent with its effects on pain sensitivity. Our results show that long term (28 days) ovariectomy (ovx) of adult rats induces a profound thermal and mechanical hyperalgesia of the hindpaw and tail compared to ovariectomized animals that were continuously estrogen-treated (ovx+E). Significant changes in the expression of two neuropeptides, substance P (SP) and calcitonin gene related peptide (CGRP), were observed using immunocytochemistry and in situ hybridization (ISH) in the small lumbar DRG neurons which contain ER. CGRP and SP were differentially regulated by estrogen, with SP showing a significant downregulation at both the peptide and mRNA level while CGRP and its mRNA were increased in the DRG of estrogen-treated animals. We also evaluated the development of mechanical allodynia after partial sciatic nerve injury and found that both ovx and ovx+E animals developed significant allodynia within a week of the partial nerve injury, which continued for at least one month. The estrogen treated animals showed a partial amelioration of the extent of the allodynia at 2 weeks post injury. Overall, the results suggest that estrogen has significant anti-nociceptive actions that can be directly correlated with changes in expression of two peptides in the small nociceptive ERα expressing neurons of the DRG.
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