(An) Investigation of the Role of TRPV1 in the Analgesic Effect of [6]-Gingerol in Oxaliplatin-Induced Neuropathic Pain

다국어 초록 (Multilingual Abstract)

All cancer treatments affect not only the cancer but also normal tissues, and side effects after anticancer drug treatment reduce the quality of life of cancer survivors. Patients treated with oxaliplatin, a well-known anticancer drug, sometimes experience acute colds and mechanical allodynia as side effects. Although various studies are being conducted in this regard, the optimal treatment has not been developed. In this study, [6]-gingerol, one of the main bioactive components of Zingiber officinale roscoe, showed an analgesic effect that dramatically alleviated oxaliplatin-induced allodynia. Cold and mechanical allodynia were assessed with the acetone drop and von Fery filament tests, respectively. In spinal cord and dorsal root ganglion (DRG) neurons, qRT-PCR and western blot showed that the mRNA and protein of transient receptor potential voltage 1 (TRPV1) were down-regulated after oxaliplatin injection and up-regulated after [6]-gingerol treatment. Administration of TRPV1 antagonist blocked the analgesic effect of [6]-gingerol. This suggests that [6]-gingerol, which is structurally similar to capsaicin, can be a good ligand for the TRPV1 receptor and can potentially be used to treat neuropathic pain.

목차 (Table of Contents)

• A list of figures · ⅲ
• Abbreviations ⅴ
• Abstract · ⅶ
• Ⅰ. Introduction · 1
• Ⅱ. Materials and Methods 4
• 2.1 Animals · 4
• 2.2 Oxaliplatin Administration 4
• 2.3 Behavior Test · 4
• 2.4 Oxaliplatin-Induced Neuropathic Pain · 5
• 2.5 Administration of [6]-gingerol · 5
• 2.6 Intraperitoneal Injection of TRPV1 Antagonist 6
• 2.7 Intrathecal Injection of TRPV1 Antagonist · 6
• 2.8 Intrathecal Injection of [6]-gingerol · 6
• 2.9 Tissue Preparation 7
• 2.10 Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR) 7
• 2.11 Western Blot 8
• 2.12 Statistical Analysis · 8
• Ⅲ. Results 9
• 3.1 Single intraperitoneal administration of oxaliplatin induced cold and
• mechanical allodynia but did not induce heat allodynia · 9
• 3.2 Effect of [6]-gingerol oxaliplatin-induced cold, mechanical, and thermal allodynia in mice 11
• 3.3 TRPV1 antagonist completely blocked the effect of [6]-gingerol · 13
• 3.4 Effect of [6]-gingerol on Trpv1 gene expression in DRG and spinal cord 15
• 3.5 Effect of [6]-gingerol TRPV1 protein expression in DRG and spinal cord 17
• 3.6 Intrathecal injection of TRPV1 antagonist completely blocked the effect of [6]-gingerol 19
• 3.7 Intrathecal injection of [6]-gingerol completely blocked the oxaliplatin-induced neuropathic pain 21
• Ⅳ. Discussion 23
• Ⅴ. Conclusion · 27
• Ⅵ. References 30
• 국문초록 · 36