MRC Centre for Reproductive Health, The University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 UK.
Centre for Integrative Physiology, The University of Edinburgh, Hugh Robson Building, 15 George Square, Edinburgh EH8 UK.
Sci Rep. 2017 Mar 10;7:44169. doi: 10.1038/srep44169.
Endometriosis is an incurable gynecological disorder characterized by debilitating pain and the establishment of innervated endometriosis lesions outside the uterus. In a preclinical mouse model of endometriosis we demonstrated overexpression of the PGE-signaling pathway (including COX-2, EP, EP) in endometriosis lesions, dorsal root ganglia (DRG), spinal cord, thalamus and forebrain. TRPV1, a PGE-regulated channel in nociceptive neurons was also increased in the DRG. These findings support the concept that an amplification process occurs along the pain neuroaxis in endometriosis. We then tested TRPV1, EP, and EP receptor antagonists: The EP antagonist was the most efficient analgesic, reducing primary hyperalgesia by 80% and secondary hyperalgesia by 40%. In this study we demonstrate reversible peripheral and central hyperalgesia in mice with induced endometriosis.
子宫内膜异位症是一种无法治愈的妇科疾病，其特征是疼痛剧烈，并在子宫外形成有神经支配的子宫内膜异位症病灶。在子宫内膜异位症的临床前小鼠模型中，我们发现在子宫内膜异位症病灶、背根神经节（DRG）、脊髓、丘脑和前脑中，PGE 信号通路（包括 COX-2、EP、EP）过度表达，伤害感受神经元中的 PGE 调节通道 TRPV1 也增加。这些发现支持这样一种概念，即在子宫内膜异位症中，疼痛神经轴沿线发生放大过程。然后，我们测试了 TRPV1、EP 和 EP 受体拮抗剂：EP 拮抗剂是最有效的镇痛药，使原发性痛觉过敏减少 80%，继发性痛觉过敏减少 40%。在这项研究中，我们在诱导子宫内膜异位症的小鼠中证明了可逆的外周和中枢痛觉过敏。
