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| 22KS-020 |
TMI-1, TNF-α-Converting Enzyme Inhibitor, Alleviates Mechanical Hyperalgesia in CINP Rat by inhibiting TLR4 Signaling
Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Busan, Korea1
Department of Anesthesia and Pain Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, Korea2
Background: Chemotherapy-induced peripheral neuropathy is challenging to treat and can adversely impact the quality of life. TNF-α contributes to CIPN by neuroinflammation and upregulation of TRPV1. The study\'s objective is to assess the analgesic effect of TMI-1, a TNF-α-converting enzyme inhibitor, and the underlying mechanism in a rat model of paclitaxel-induced neuropathic pain (PINP).
Materials and Methods: Rats received intraperitoneal injections of 4 mg/kg paclitaxel on days 0, 2, 4, and 6 and received single or multiple intraperitoneal injections of TMI-1 at various times. The mechanical thresholds, TNF-α, TNFR, PI3K, phospho-Akt, TRPV1, TLR4, and Cav 3.2 were assessed with behavioral testing, Western blotting, RT-PCR, ELISA, and immunohistochemistry in lumbar DRG.
Result: Single and multiple injections of TMI-1 reduced mechanical hyperalgesia. Paclitaxel significantly increased, and TMI-1 subsequently decreased, the expression levels of TNF-α, TNFR, PI3K, phospho-Akt, TRPV1, TLR4, and Cav 3.2 in the lumbar DRG. In addition, TMI-1 showed an analgesic effect by inhibiting TLR4 signaling and secretion of TNF-α.
Conclusion: TMI-1 alleviated PINP by reversing the upregulation of TRPV1 and decreasing levels of TNF-α through TLR4 signaling in the rat model of PINP.
Materials and Methods: Rats received intraperitoneal injections of 4 mg/kg paclitaxel on days 0, 2, 4, and 6 and received single or multiple intraperitoneal injections of TMI-1 at various times. The mechanical thresholds, TNF-α, TNFR, PI3K, phospho-Akt, TRPV1, TLR4, and Cav 3.2 were assessed with behavioral testing, Western blotting, RT-PCR, ELISA, and immunohistochemistry in lumbar DRG.
Result: Single and multiple injections of TMI-1 reduced mechanical hyperalgesia. Paclitaxel significantly increased, and TMI-1 subsequently decreased, the expression levels of TNF-α, TNFR, PI3K, phospho-Akt, TRPV1, TLR4, and Cav 3.2 in the lumbar DRG. In addition, TMI-1 showed an analgesic effect by inhibiting TLR4 signaling and secretion of TNF-α.
Conclusion: TMI-1 alleviated PINP by reversing the upregulation of TRPV1 and decreasing levels of TNF-α through TLR4 signaling in the rat model of PINP.