Epiregulin and EGFR interactions are involved in pain processing
Epiregulin and EGFR interactions are involved in pain processing
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DOI：
10.1172/jci87406
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发表时间：
2017-09-01
影响因子：
15.9
通讯作者：
Diatchenko, Luda
中科院分区：
文献类型：
--
作者：
Martin, Loren J.;Smith, Shad B.;Diatchenko, Luda
EGFR属于研究充分的受体酪氨酸激酶ErbB家族。EGFR被许多促进细胞生长、增殖和组织再生的内源性配体激活。在本研究中，我们已经证明了EGFR及其天然配体epiregulin（EREG）在疼痛处理中的作用。我们发现，在炎症和慢性疼痛的小鼠模型中，用临床上可用的化合物抑制EGFR强烈降低了疼痛反应行为。EGFR介导的EGFR激活通过涉及PI 3 K/AKT/mTOR通路和基质金属蛋白酶-9的机制增强伤害感受。此外，EREG应用增强辣椒素诱导的感觉神经元的一个子集的钙内流。EGFR和EREG基因均显示与颞下颌关节紊乱病的几个临床队列中慢性疼痛的发展存在遗传关联。因此，EGFR和EREG可能是持续性疼痛病症的合适治疗靶点。
The EGFR belongs to the well-studied ErbB family of receptor tyrosine kinases. EGFR is activated by numerous endogenous ligands that promote cellular growth, proliferation, and tissue regeneration. In the present study, we have demonstrated a role for EGFR and its natural ligand, epiregulin (EREG), in pain processing. We show that inhibition of EGFR with clinically available compounds strongly reduced nocifensive behavior in mouse models of inflammatory and chronic pain. EREGmediated activation of EGFR enhanced nociception through a mechanism involving the PI3K/AKT/mTOR pathway and matrix metalloproteinase-9. Moreover, EREG application potentiated capsaicin-induced calcium influx in a subset of sensory neurons. Both the EGFR and EREG genes displayed a genetic association with the development of chronic pain in several clinical cohorts of temporomandibular disorder. Thus, EGFR and EREG may be suitable therapeutic targets for persistent pain conditions.