Distinct TRPV1- and TRPA1-based mechanisms underlying enhancement of oral ulcerative mucositis-induced pain by 5-fluorouracil

Pain
Kiichiro YamaguchiKiyotoshi Inenaga

Abstract

In many patients with cancer, chemotherapy-induced severe oral ulcerative mucositis causes intractable pain, leading to delays and interruptions in therapy. However, the pain mechanism in oral ulcerative mucositis after chemotherapy has not been extensively studied. In this study, we investigated spontaneous pain and mechanical allodynia in a preclinical model of oral ulcerative mucositis after systemic administration of the chemotherapy drug 5-fluorouracil, using our proprietary pain assay system for conscious rats. 5-Fluorouracil caused leukopenia but did not induce pain-related behaviors. After 5-fluorouracil administration, oral ulcers were developed with topical acetic acid treatment. Compared with saline-treated rats, 5-fluorouracil-exposed rats showed more severe mucositis with excessive bacterial loading due to a lack of leukocyte infiltration, as well as enhancements of spontaneous pain and mechanical allodynia. Antibacterial drugs, the lipid A inhibitor polymyxin B and the TRPV1/TRPA1 channel pore-passing anesthetic QX-314, suppressed both the spontaneous pain and the mechanical allodynia. The cyclooxygenase inhibitor indomethacin and the TRPV1 antagonist SB-366791 inhibited the spontaneous pain, but not the mechanica...Continue Reading

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Citations

Mar 9, 2018·Journal of Dental Research·T NodaiK Inenaga
Oct 10, 2018·Integrative Cancer Therapies·Jae-Woo ParkJinsung Kim
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Sep 30, 2021·Journal of Oral Rehabilitation·Ziwei TangFan Jian

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