Epidermal growth factor receptor signaling modulates postoperative pain and inflammatory responses

Abstract

Postoperative pain (POP) arises from the activation and dysregulation of nociceptive pathways following tissue injury. Although it plays a protective role by signaling potential harm and preventing further damage, POP can become maladaptive when inflammatory and neural processes intensify or prolong pain signaling. Surgical trauma triggers an immune response that sensitizes nociceptors, lowering the threshold for pain. Simultaneously, acute inflammation skews the balance between pain facilitation and inhibition in favor of pain facilitation, resulting in central sensitization and subsequent chronic postoperative pain. Emerging evidence indicates that inhibition of the EGFR signaling pathway may offer a novel therapeutic approach for pain management. This is supported by preclinical and clinical data showing robust analgesic and anti-inflammatory effects in chronic pain contexts. Furthermore, the EGFR-activated PI3K-Akt-mTOR pathway has been implicated in rodent models of postoperative pain. Despite these promising findings, conclusive data regarding the analgesic efficacy of this pathway in postoperative recovery remains limited. EGFR inhibition may mitigate the substantial adverse effects of current pain medicines, thereby addressing a critical unmet need in clinical pain management. This review explores the role of EGFR pathways in pain and inflammation, with an emphasis on its interaction with other receptors and how these interactions influence tissue survival and inflammatory processes.