Transient Receptor Potential Vanilloid 1 is Essential for Cisplatin-Induced Heat Hyperalgesia in Mice
Open Access
- 1 January 2010
- journal article
- Published by SAGE Publications in Molecular Pain
- Vol. 6, 15
- https://doi.org/10.1186/1744-8069-6-15
Abstract
Background: Cisplatin is primarily used for treatment of ovarian and testicular cancer. Oxaliplatin is the only effective treatment for metastatic colorectal cancer. Both are known to cause dose related, cumulative toxic effects on the peripheral nervous system and thirty to forty percent of cancer patients receiving these agents experience painful peripheral neuropathy. The mechanisms underlying painful platinum-induced neuropathy remain poorly understood. Previous studies have demonstrated important roles for TRPV1, TRPM8, and TRPA1 in inflammation and nerve injury induced pain. Results: In this study, using real-time, reverse transcriptase, polymerase chain reaction (RT-PCR), we analyzed the expression of TRPV1, TRPM8, and TRPA1 induced by cisplatin or oxaliplatin in vitro and in vivo. For in vitro studies, cultured E15 rat dorsal root ganglion (DRG) neurons were treated for up to 48 hours with cisplatin or oxaliplatin. For in vivo studies, trigeminal ganglia (TG) were isolated from mice treated with platinum drugs for three weeks. We show that cisplatin and oxaliplatin-treated DRG neurons had significantly increased in TRPV1, TRPA1, and TRPM8 mRNA expression. TG neurons from cisplatin treated mice had significant increases in TRPV1 and TRPA1 mRNA expression while oxaliplatin strongly induced only TRPA1. Furthermore, compared to the cisplatin-treated wild-type mice, cisplatin-treated TRPV1-null mice developed mechanical allodynia but did not exhibit enhancement of noxious heat- evoked pain responses. Immunohistochemistry studies showed that cisplatin-treated mice had no change in the proportion of the TRPV1 immunopositive TG neurons. Conclusion: These results indicate that TRPV1 and TRPA1 could contribute to the development of thermal hyperalgesia and mechanical allodynia following cisplatin-induced painful neuropathy but that TRPV1 has a crucial role in cisplatin-induced thermal hyperalgesia in vivo.Keywords
This publication has 88 references indexed in Scilit:
- Comparison of Oxaliplatin- and Cisplatin-Induced Painful Peripheral Neuropathy in the RatThe Journal of Pain, 2009
- Group II metabotropic glutamate receptor activation on peripheral nociceptors modulates TRPV1 functionBrain Research, 2009
- Behavioral and electrophysiological studies in rats with cisplatin-induced chemoneuropathyBrain Research, 2008
- HC-030031, a TRPA1 Selective Antagonist, Attenuates Inflammatory- and Neuropathy-Induced Mechanical HypersensitivityMolecular Pain, 2008
- TRPA1 mediates formalin-induced painProceedings of the National Academy of Sciences of the United States of America, 2007
- 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1Proceedings of the National Academy of Sciences of the United States of America, 2007
- A Role of TRPA1 in Mechanical Hyperalgesia is Revealed by Pharmacological InhibitionMolecular Pain, 2007
- TRP channel activation by reversible covalent modificationProceedings of the National Academy of Sciences of the United States of America, 2006
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- Ethical guidelines for investigations of experimental pain in conscious animalsPain, 1983