Matrix metalloproteinase 9 expressed in satellite glial cells in the trigeminal ganglion contributes to tongue-cancer-associated pain

Objectives: Matrix metalloproteinase 9 (MMP9) degrades extracellular matrix and it is involved in cancer angiogenesis, invasion, and metastasis. However, the function of MMP9 within the trigeminal ganglion (TG) in tongue-cancer-associated pain remains unclear. The objective of this study was to clarify the role of MMP9 in the TG in tongue-cancer-associated pain in rats. Methods: Tongues were inoculated with squamous cell carcinoma (SCC) cells. Post–SCC inoculation, the tongues were subjected to mechanical stimulation using flat-tipped forceps and the mechanical head-withdrawal reflex threshold (MHWT) was measured. On Day 6, post-inoculation, the localization of MMP9 in the TG was identified, and its expression level was quantified. Additionally, MMP9 inhibitors were administered daily to the TG, post–SCC inoculation, and the MHWT was measured. Furthermore, MMP9 was administered daily to the TG of untreated rats, and the MHWT was measured. Results: The MHWT decreased from Day 1, post–SCC inoculation. Activated satellite glial cells expressed MMP9, and the MMP9 level increased. Inhibition of MMP9 in the TG prevented the SCC-induced decrease in the MHWT from Day 6 onwards. Conversely, the administration of MMP9 to the TG led to a reduction in the MHWT in untreated rats. Conclusion: MMP9, which originates from activated satellite glial cells in the TG, post–SCC inoculation, contributes to tongue-cancer-associated pain.