The aim of this study was to investigate the mechanism of TRPM8 in neuroproliferation and pain, as well as the relevance of the Akt/mTOR signaling pathway in mice with IC/BPS.
The model of IC/BPS was established in wild and TRPM8-/- mice. The mechanical sensitivity was measured. The number of neurite segments, length of neurites, and density of neurites were all counted. IL-6 and norepinephrine levels were detected by ELISA, Western blot was used to detect protein levels of TRPM8, Akt, p-Akt, mTOR, p-mTOR. Immunofluorescence was used to detect TRPM8 expression and distribution in neurites, neurons, and sensory nerves in mouse bladder tissue.
Pain threshold in the IC/BPS group was decreased, and neurite segments, length, and density were all significantly enhanced when compared to the control group. The parameters in the IC/BPS model + Menthol group were more statistically significant. Neurite number and density were lower in TRPM8 knockout-model mice than in IC/BPS model mice. The expression of TRPM8 and the ratios of p-Akt/Akt and p-mTOR/mTOR rose in the IC/BPS model group. In TRPM8 knockout-model mice, the ratios of p-Akt/Akt and p-mTOR/mTOR were not substantially different from those in the control group. TRPM8 knockout-model mice had considerably lower levels of serum IL-6 and urine norepinephrine than IC/BPS model mice.
TRPM8 can induce pain hypersensitivity and sensory nerve proliferation by activating Akt/mTOR pathway and raising the expression of IL-6 and norepinephrine in IC/BPS models. These findings offer new perspectives on IC/BPS treatment.
Lower urinary tract symptoms. 2024 Nov [Epub]
Liyang Wu, Ran Chang, Peng Zhang
Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China., Urologic Rehabilitation Department, Beijing Boai Hospital, China Rehabilitation Research Center, Beijing, China.