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. EREG-mediated 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.

中文翻译：

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上皮调节蛋白和 EGFR 相互作用参与疼痛处理

EGFR 属于经过充分研究的 ErbB 受体酪氨酸激酶家族。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 及其天然配体上皮调节蛋白 (EREG) 在疼痛处理中的作用。我们表明，用临床可用的化合物抑制 EGFR 可大大降低炎症和慢性疼痛小鼠模型中的伤害行为。EREG 介导的 EGFR 激活通过涉及 PI3K/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 应用增强了辣椒素诱导的一部分感觉神经元中的钙内流。EGFR和EREG _在几个颞下颌关节紊乱的临床队列中，基因显示出与慢性疼痛发展的遗传关联。因此，EGFR 和 EREG 可能是持续性疼痛状况的合适治疗靶点。