Borges Jazlyn P, Mekhail Katrina, Fairn Gregory D, Antonescu Costin N, Steinberg Benjamin E
Neurosciences and Mental Health Program, The Hospital for Sick Children, Toronto, ON, Canada.
Department of Physiology, University of Toronto, Toronto, ON, Canada.
Front Pharmacol. 2021 May 12;12:642820. doi: 10.3389/fphar.2021.642820. eCollection 2021.
Chronic pain has been widely recognized as a major public health problem that impacts multiple aspects of patient quality of life. Unfortunately, chronic pain is often resistant to conventional analgesics, which are further limited by their various side effects. New therapeutic strategies and targets are needed to better serve the millions of people suffering from this devastating disease. To this end, recent clinical and preclinical studies have implicated the epidermal growth factor receptor signaling pathway in chronic pain states. EGFR is one of four members of the ErbB family of receptor tyrosine kinases that have key roles in development and the progression of many cancers. EGFR functions by activating many intracellular signaling pathways following binding of various ligands to the receptor. Several of these signaling pathways, such as phosphatidylinositol 3-kinase, are known mediators of pain. EGFR inhibitors are known for their use as cancer therapeutics but given recent evidence in pilot clinical and preclinical investigations, may have clinical use for treating chronic pain. Here, we review the clinical and preclinical evidence implicating EGFR in pathological pain states and provide an overview of EGFR signaling highlighting how EGFR and its ligands drive pain hypersensitivity and interact with important pain pathways such as the opioid system.
慢性疼痛已被广泛认为是一个重大的公共卫生问题，它会影响患者生活质量的多个方面。不幸的是，慢性疼痛通常对传统镇痛药有抗性，而传统镇痛药又因其各种副作用受到进一步限制。需要新的治疗策略和靶点来更好地服务于数百万患有这种毁灭性疾病的人。为此，最近的临床和临床前研究表明表皮生长因子受体信号通路与慢性疼痛状态有关。表皮生长因子受体（EGFR）是受体酪氨酸激酶ErbB家族的四个成员之一，在许多癌症的发生和发展中起关键作用。EGFR通过多种配体与受体结合后激活许多细胞内信号通路发挥作用。这些信号通路中的几种，如磷脂酰肌醇3激酶，是已知的疼痛介质。EGFR抑制剂以其作为癌症治疗药物而闻名，但鉴于最近在初步临床和临床前研究中的证据，可能在治疗慢性疼痛方面有临床应用价值。在此，我们综述了表明EGFR与病理性疼痛状态有关的临床和临床前证据，并概述了EGFR信号通路，强调EGFR及其配体如何驱动疼痛超敏反应以及与阿片系统等重要疼痛通路相互作用。
