[Abstract Title]. - Society for Neuroscience

Topic: D.08.l. Neuropathic pain: Mechanisms
Support: NIH R01 NS 40471-04
NIH K08 DE14571-05
Title: TRPV1 and TRPA1 contribute to thermal hyperalgesia and mechanical allodynia in
platinum drug-induced neuropathy in mice
Authors: *A. J. BIEBER, L. E. TA, P. A. LOW, A. J. WINDEBANK;
Mol. Neurosci. Program, and Dept. of Neurol., Mayo Clin. Col. of Med., Rochester, MN
Abstract: 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 30-40% of cancer patients
receiving these agents experience painful peripheral neuropathy. The mechanisms underlying
painful platinum-induced neuropathy remain poorly understood. Previous studies demonstrated
important roles for TRPV1, TRPM8, and TRPA1 in inflammation and injury-induced pain. 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 ganglions (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 cis- or oxalplatin for three weeks. We showed that
cis- and oxaliplatin-treated DRG neurons had significant increase in TRPV1, TRPA1, and
TRPM8 mRNA expressions. TG neurons from cisplatin-treated mice had significant increase in
TRPV1 and TRPA1 mRNA expressions. Furthermore, compared to the cisplatin-treated wildtype
mice, cisplatin-treated TRPV1-null mice sustained mechanical allodynia but did not exhibit
enhancement of thermally evoked responses. These results indicate that TRPV1 and TRPA1
could contribute to the development of thermal hyperalgesia and mechanical allodynia following
cisplatin-induced painful neuropathy.
Disclosures: A.J. Bieber, None; L.E. Ta, None; P.A. Low, None; A.J. Windebank, None.
Poster
268. Neuropathic Pain Mechanisms: Ion Channels
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 268.7/GG4
Topic: D.08.l. Neuropathic pain: Mechanisms