Mechanism of EGFR-targeted drugs for pain relief in oral cancer

doi:10.19438/j.cjoms.2022.03.002

Abstract

Abstract: PURPOSE: The purpose of this study was to investigate whether drugs targeting EGFR (erlotinib, Nimotuzumab) could affect the pain threshold of experimental animals and to preliminarily explore the mechanism. METHODS: Naive mice were divided into two groups(physiological saline, n=6; erlotinib, n=6), the difference of pain threshold between the two groups was compared by Von Frey fiber test, hot plate test and 5% formalin test 1 h after administration. Nude mice were selected and divided into 3 groups (Sham + NS group, n=10; Plantar neoplasia + NS group, n=10; Plantar neoplasia + Nimotuzumab group, n=10). The mechanical pain threshold and thermal pain threshold of the mice were detected 1d before modeling and 1, 5, 7, 10 and 14 d after modeling. The mouse feet were dissected 14 days later, and the concentrations of IL-1β and IL-6 were detected by ELISA after tissue homogenization. The data were processed by Graphpad Prism statistical software. RESULTS: After erlotinib injection, the mechanical pain threshold and thermal pain threshold of mice had no obvious changes. After injection of 5% formalin in mice, the duration of licking in the anterior phase (0-10 min, P<0.01) and posterior phase (10-60 min, P<0.01) decreased significantly. Heat and mechanical pain sensitivity could be induced after plantar tumor formation in nude mice. Nimotuzumab slowed down tumor growth rate and increased thermal pain threshold (P<0.05) and mechanical pain threshold (P<0.05) in plantar tumorigenic mice. ELISA showed that the concentration of IL-1β (P<0.05) and IL-6 (P<0.05) in the plantar tissue of mice in the Nimotuzumab treatment group was significantly lower than that of the PBS treatment group. CONCLUSIONS: Erlotinib can alleviate pain induced by formalin in mice. Nimotuzumab can reduce mechanical and thermal pain sensitivity induced by plantar tumor formation, and the mechanism may be related to the decrease of inflammatory cytokines in local tissues. EGFR-targeted drugs may be one of the good analgesics for patients with advanced cancer pain.

Key words: Nimotuzumab, Erlotinib, Pain, Oral squamous cell carcinoma

CLC Number:

R739.8

WEI Dong-liang, LI Zhi, JU Hou-yu, WU Yun-teng, GUO Wei, REN Guo-xin. Mechanism of EGFR-targeted drugs for pain relief in oral cancer[J]. China Journal of Oral and Maxillofacial Surgery, 2022, 20(3): 219-224.

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