Programmed Cell Death Protein 1 Contributes to Oral Cancer Pain via Regulating Tumor Necrosis Factor Alpha in the Spinal Trigeminal Nucleus Caudalis.

Autor:	Mao R; Department of Biomedical Sciences, Texas A&M University School of Dentistry, Dallas, Texas, USA., Liu S; Department of Biomedical Sciences, Texas A&M University School of Dentistry, Dallas, Texas, USA., Dolan JC; NYU Dentistry Translational Research Center, New York University College of Dentistry, New York, NY, USA., Schmidt BL; NYU Dentistry Translational Research Center, New York University College of Dentistry, New York, NY, USA.; Pain Research Center, New York University, New York, NY, USA., Tao F; Department of Biomedical Sciences, Texas A&M University School of Dentistry, Dallas, Texas, USA.
Jazyk:	angličtina
Zdroj:	Current neuropharmacology [Curr Neuropharmacol] 2024 Dec 09. Date of Electronic Publication: 2024 Dec 09.
DOI:	10.2174/1570159X23666241209160039
Abstrakt:	Background: Oral cancer causes intense pain at the primary site, and such pain can impair oral functions. However, the underlying mechanisms for oral cancer pain are still not fully understood. In the present study, it is investigated whether programmed cell death protein 1 (PD-1) is involved in the development of oral cancer pain. Methods: RMP1-14, a specific anti-PD-1 antibody, was injected into spinal trigeminal nucleus caudalis (Sp5C) and measured pain behaviors using von Frey filaments and dolognawmeter. Western blotting and immunofluorescence staining were performed to analyze the expression of PD-1 and tumor necrosis factor alpha (TNFα) in the Sp5C. Results: It was observed that the PD-1 antibody significantly inhibited mechanical hypersensitivity and functional allodynia in our oral cancer pain mouse model. Moreover, we found that TNFα was highly upregulated in the Sp5C following the induction of oral cancer pain and that intra-Sp5C injection of the PD-1 antibody diminished the upregulation of TNFα. It was found that genetic deletion of TNFα or its receptor antagonism synergized the analgesic effect of PD-1 antibody on oral cancer pain. Conclusion: Our results suggest that PD-1 in the Sp5C contributes to oral cancer pain by altering TNFα signaling in the trigeminal nociceptive system, and PD-1 could be targeted to develop a novel approach for oral cancer pain management. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
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