Screening the role of pronociceptive molecules in a rodent model of endometriosis pain.
Screening the role of pronociceptive molecules in a rodent model of endometriosis pain.
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DOI：
10.1016/j.jpain.2014.04.002
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发表时间：
2014-07
期刊：
影响因子：
4
通讯作者：
Levine, Jon D.
中科院分区：
文献类型：
--
作者：
Alvarez, Pedro;Levine, Jon D.
慢性疼痛是子宫内膜异位症患者的主要症状，子宫内膜异位症是影响育龄妇女的常见妇科疾病。虽然子宫内膜异位症病变产生许多促痛物质，但仍缺乏支持其相对作用的实验证据。此外，目前还不清楚这些促痛剂是否直接激活伤害感受器诱导子宫内膜异位症疼痛。为了确定它们对子宫内膜异位症相关疼痛的相对作用，我们评价了鞘内注射寡脱氧核苷酸反义mRNA，该反义mRNA是已知由异位子宫内膜产生的三种伤害感受介质的受体。将自体子宫组织植入腓肠肌两周后，在手术大鼠中观察到局部机械性痛觉过敏。鞘内反义寡脱氧核苷酸（AS ODN）靶向mRNA的白细胞介素6受体信号复合物亚基糖蛋白130和神经生长因子酪氨酸激酶受体A（TrkA），但不是他们的错配ODN，可逆性衰减机械性痛觉过敏在植入部位。相反，在该模型中，以肿瘤坏死因子受体1（TNFR 1）为靶点的鞘内AS ODN在显著抑制肌内注射TNFα的剂量下仅具有较小的抗痛觉过敏作用。这些结果表明异位子宫内膜组织产生的致痛介质对子宫内膜异位症疼痛的相对贡献。这里提出的实验方法提供了一种新的方法来评估其他疼痛病变以及子宫内膜异位症的解决方案病变作为新的治疗疼痛综合征的目标所产生的介质的差异贡献。本文提出的证据，亲痛觉介质的相对贡献，以显示大鼠子宫内膜异位症疼痛模型的原发性痛觉过敏。这种方法可用于确定治疗子宫内膜异位症疼痛的潜在靶点。
Chronic pain is a major symptom in patients with endometriosis, a common gynecologic condition affecting women in their reproductive years. While many pro-algesic substances are produced by endometriosis lesions, experimental evidence supporting their relative roles is still lacking. Furthermore, it is unclear whether these pro-algesic agents directly activate nociceptors to induce endometriosis pain. To determine their relative contribution to pain associated with endometriosis we evaluated the intrathecal administration of oligodeoxynucleotides antisense to mRNA for receptors for three pro-nociceptive mediators known to be produced by ectopic endometrium. Two weeks after the implant of autologous uterine tissue onto the gastrocnemius muscle, local mechanical hyperalgesia was observed in operated rats. Intrathecal antisense oligodeoxynucleotides (AS ODN) targeting mRNA for the interleukin 6 receptor-signaling complex subunit glycoprotein 130 and the NGF tyrosine kinase receptor A (TrkA), but not their mismatch ODNs, reversibly attenuated mechanical hyperalgesia at the implant site. In contrast, intrathecal AS ODN targeting the tumor necrosis factor receptor 1 (TNFR1), at a dose that markedly inhibited intramuscularly injected TNFα had only a small antihyperalgesic effect in this model. These results indicate the relative contribution of pronociceptive mediators produced by ectopic endometrial tissue to endometriosis pain. The experimental approach presented here provides a novel method to evaluate for the differential contribution of mediators produced by other painful lesions as well as endometriosis solutions lesions as targets for novel treatment of pain syndromes. This article presents evidence for the relative contribution of pro-algesic mediators to primary hyperalgesia displayed by rats submitted to a model of endometriosis pain. This approach can be used to identify potential targets for the treatment of endometriosis pain.
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影响因子：
7.4
作者：
Deising, Saskia;Weinkauf, Benjamin;Rukwied, Roman
通讯作者：
Rukwied, Roman
DOI：
10.3415/vcot-10-04-0051
发表时间：
2011-01-01
影响因子：
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DOI：
10.1523/jneurosci.3229-12.2013
发表时间：
2013-02-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Joseph EK;Green PG;Bogen O;Alvarez P;Levine JD
通讯作者：
Levine JD
影响因子：
4.1
作者：
Fambrini, Massimiliano;Andersson, Karin Louise;Scarselli, Gianfranco
通讯作者：
Scarselli, Gianfranco