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ERK 在纤维肌痛疼痛的性别差异中的作用。

Role of ERK in gender difference of fibromyalgia pain.

机构信息

Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.

Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan.

出版信息

Mol Pain. 2024 Jan-Dec;20:17448069241261940. doi: 10.1177/17448069241261940.

DOI:10.1177/17448069241261940
PMID:38818809
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11168046/
Abstract

This study investigated the ERK pathway of the peripheral nervous system and discovered a gender-specific pattern of ERK activation in the dorsal root ganglion of an acid-induced chronic widespread muscular pain model. We employed a twice acid-induced chronic musculoskeletal pain model in rats to evaluate mechanical pain behavior in both male and female groups. We further conducted protein analysis of dissected dorsal root ganglions from both genders. Both male and female rats exhibited a similar pain behavior trend, with females demonstrating a lower pain threshold. Protein analysis of the dorsal root ganglion (DRG) showed a significant increase in phosphorylated ERK after the second acid injection in all groups. However, phosphorylation of ERK was observed in the dorsal root ganglion, with higher levels in the male ipsilateral group compared to the female group. Moreover, there was a no difference between the left and right sides in males, whereas the significant difference was observed in females. In conclusions, the administration of acid injections induced painful behavior in rats, and concurrent with this, a significant upregulation of pERK was observed in the dorsal root ganglia, with a greater magnitude of increase in males than females, and in the contralateral side compared to the ipsilateral side. Our findings shed light on the peripheral mechanisms underlying chronic pain disorders and offer potential avenues for therapeutic intervention.

摘要

本研究调查了周围神经系统的 ERK 通路,并在酸诱导的慢性广泛性肌肉疼痛模型的背根神经节中发现了 ERK 激活的性别特异性模式。我们在大鼠中使用了两次酸诱导的慢性肌肉骨骼疼痛模型,以评估男性和女性组的机械性疼痛行为。我们进一步对来自两性的解剖背根神经节进行了蛋白质分析。雄性和雌性大鼠均表现出相似的疼痛行为趋势,而雌性大鼠的疼痛阈值较低。背根神经节(DRG)的蛋白质分析显示,所有组在第二次酸注射后 ERK 的磷酸化都显著增加。然而,在背根神经节中观察到 ERK 的磷酸化,雄性同侧组的磷酸化水平明显高于雌性组。此外,雄性的左右两侧没有差异,而雌性则存在显著差异。总之,酸注射给药会在大鼠中引起疼痛行为,同时在背根神经节中观察到 pERK 的显著上调,雄性的上调幅度大于雌性,并且在对侧侧比同侧侧更大。我们的发现揭示了慢性疼痛障碍的外周机制,并为治疗干预提供了潜在途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf7/11168046/0870d6dfc234/10.1177_17448069241261940-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf7/11168046/ac42ec077deb/10.1177_17448069241261940-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf7/11168046/5732c04e5c6a/10.1177_17448069241261940-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf7/11168046/f3189ef33d9e/10.1177_17448069241261940-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf7/11168046/60381bf214a4/10.1177_17448069241261940-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf7/11168046/5b7bd6473bf7/10.1177_17448069241261940-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf7/11168046/39ec436a858a/10.1177_17448069241261940-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf7/11168046/0870d6dfc234/10.1177_17448069241261940-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf7/11168046/ac42ec077deb/10.1177_17448069241261940-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf7/11168046/5732c04e5c6a/10.1177_17448069241261940-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf7/11168046/f3189ef33d9e/10.1177_17448069241261940-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf7/11168046/60381bf214a4/10.1177_17448069241261940-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf7/11168046/5b7bd6473bf7/10.1177_17448069241261940-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf7/11168046/39ec436a858a/10.1177_17448069241261940-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf7/11168046/0870d6dfc234/10.1177_17448069241261940-fig7.jpg

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Healthcare (Basel). 2023 Jan 11;11(2):223. doi: 10.3390/healthcare11020223.
2
Ovarian Hormone-dependent and Spinal ERK Activation-regulated Nociceptive Hypersensitivity in Female Rats with Acid Injection-induced Chronic Widespread Muscle Pain.酸注射诱导的慢性广泛性肌肉疼痛的雌性大鼠中卵巢激素依赖和脊髓 ERK 激活调节的痛觉过敏。
Sci Rep. 2019 Feb 28;9(1):3077. doi: 10.1038/s41598-019-39472-z.
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Gender Differences in the Prevalence of Fibromyalgia and in Concomitant Medical and Psychiatric Disorders: A National Veterans Health Administration Study.
性别差异与纤维肌痛的患病率以及同时存在的医学和精神障碍:一项全国退伍军人健康管理局的研究。
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Nerve growth factor-induced synapse-like structures in contralateral sensory ganglia contribute to chronic mirror-image pain.神经生长因子诱导对侧感觉神经节中形成的突触样结构会导致慢性镜像疼痛。
Pain. 2015 Nov;156(11):2295-2309. doi: 10.1097/j.pain.0000000000000280.
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