Title: A Novel Model of Cancer-Induced Peripheral Neuropathy and the Role of TRPA1 in Pain Transduction,
Abstract: Background. Models of cancer-induced neuropathy are designed by injecting
cancer cells near the peripheral nerves. The interference of tissue-resident
immune cells does not allow a direct contact with nerve fibres which affects
the tumor microenvironment and the invasion process. Methods. Anaplastic
tumor-1 (AT-1) cells were inoculated within the sciatic nerves (SNs) of male
Copenhagen rats. Lumbar dorsal root ganglia (DRGs) and the SNs were collected
on days 3, 7, 14, and 21. SN tissues were examined for morphological changes
and DRG tissues for immunofluorescence, electrophoretic tendency, and mRNA
quantification. Hypersensitivities to cold, mechanical, and thermal stimuli
were determined. HC-030031, a selective TRPA1 antagonist, was used to treat
cold allodynia. Results. Nociception thresholds were identified on day 6.
Immunofluorescent micrographs showed overexpression of TRPA1 on days 7 and 14
and of CGRP on day 14 until day 21. Both TRPA1 and CGRP were coexpressed on the
same cells. Immunoblots exhibited an increase in TRPA1 expression on day 14.
TRPA1 mRNA underwent an increase on day 7 (normalized to 18S). Injection of
HC-030031 transiently reversed the cold allodynia. Conclusion. A novel and a
promising model of cancer-induced neuropathy was established, and the role of
TRPA1 and CGRP in pain transduction was examined.