Transient Receptor Potential Vanilloid 1 is essential for cisplatin-induced heat hyperalgesia in mice

Lauren E. Ta, Allan J. Bieber, Susan M. Carlton, Charles L. Loprinzi, Philip A. Low, Anthony J. Windebank

    Research output: Contribution to journalArticle

    111 Citations (Scopus)

    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.

    Original languageEnglish (US)
    Article number15
    JournalMolecular Pain
    Volume6
    DOIs
    StatePublished - Mar 5 2010

    Fingerprint

    oxaliplatin
    Hyperalgesia
    Cisplatin
    Hot Temperature
    Trigeminal Ganglion
    Neurons
    Spinal Ganglia
    Platinum
    vanilloid receptor subtype 1
    Pain
    Messenger RNA
    Poisons
    Testicular Neoplasms
    Peripheral Nervous System
    Proxy
    Peripheral Nervous System Diseases
    Reverse Transcriptase Polymerase Chain Reaction
    Ovarian Neoplasms
    Colorectal Neoplasms
    Immunohistochemistry

    ASJC Scopus subject areas

    • Anesthesiology and Pain Medicine
    • Molecular Medicine
    • Cellular and Molecular Neuroscience

    Cite this

    Ta, L. E., Bieber, A. J., Carlton, S. M., Loprinzi, C. L., Low, P. A., & Windebank, A. J. (2010). Transient Receptor Potential Vanilloid 1 is essential for cisplatin-induced heat hyperalgesia in mice. Molecular Pain, 6, [15]. https://doi.org/10.1186/1744-8069-6-15

    Transient Receptor Potential Vanilloid 1 is essential for cisplatin-induced heat hyperalgesia in mice. / Ta, Lauren E.; Bieber, Allan J.; Carlton, Susan M.; Loprinzi, Charles L.; Low, Philip A.; Windebank, Anthony J.

    In: Molecular Pain, Vol. 6, 15, 05.03.2010.

    Research output: Contribution to journalArticle

    Ta, Lauren E. ; Bieber, Allan J. ; Carlton, Susan M. ; Loprinzi, Charles L. ; Low, Philip A. ; Windebank, Anthony J. / Transient Receptor Potential Vanilloid 1 is essential for cisplatin-induced heat hyperalgesia in mice. In: Molecular Pain. 2010 ; Vol. 6.
    @article{ea94a4feaccb4599a229c37f7d70be5d,
    title = "Transient Receptor Potential Vanilloid 1 is essential for cisplatin-induced heat hyperalgesia in mice",
    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.",
    author = "Ta, {Lauren E.} and Bieber, {Allan J.} and Carlton, {Susan M.} and Loprinzi, {Charles L.} and Low, {Philip A.} and Windebank, {Anthony J.}",
    year = "2010",
    month = "3",
    day = "5",
    doi = "10.1186/1744-8069-6-15",
    language = "English (US)",
    volume = "6",
    journal = "Molecular Pain",
    issn = "1744-8069",
    publisher = "BioMed Central",

    }

    TY - JOUR

    T1 - Transient Receptor Potential Vanilloid 1 is essential for cisplatin-induced heat hyperalgesia in mice

    AU - Ta, Lauren E.

    AU - Bieber, Allan J.

    AU - Carlton, Susan M.

    AU - Loprinzi, Charles L.

    AU - Low, Philip A.

    AU - Windebank, Anthony J.

    PY - 2010/3/5

    Y1 - 2010/3/5

    N2 - 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.

    AB - 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.

    UR - http://www.scopus.com/inward/record.url?scp=77951173732&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=77951173732&partnerID=8YFLogxK

    U2 - 10.1186/1744-8069-6-15

    DO - 10.1186/1744-8069-6-15

    M3 - Article

    C2 - 20205720

    AN - SCOPUS:77951173732

    VL - 6

    JO - Molecular Pain

    JF - Molecular Pain

    SN - 1744-8069

    M1 - 15

    ER -