A Novel Model of Cancer-Induced Peripheral Neuropathy and the Role of TRPA1 in Pain Transduction.

Ahmad Maqboul,Bakheet Elsadek

doi:10.1155/2017/3517207

Ahmad Maqboul, Bakheet Elsadek

Open Access

https://doi.org/10.1155/2017/3517207

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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.

Highlights

Tumors spread through vascular, lymphatic, and/or neural routes. e latter is characteristic in cases of head and neck, pancreas, colon, rectum, prostate, biliary tract, and stomach cancers [1]
Cancer-induced neuropathy was modeled by injecting cancer cells in the proximity of the sciatic nerve (SN) [6, 7], promoting such models to study the invasion of malignant cells
To overcome the interference of these tissue-resident immune cells, which affects the onset of cancer pain and the regulation of the proteins involved in the invasion process, we introduce a novel cancer-induced neuropathic pain model

Summary

Introduction

Lymphatic, and/or neural routes. e latter is characteristic in cases of head and neck, pancreas, colon, rectum, prostate, biliary tract, and stomach cancers [1]. To overcome the interference of these tissue-resident immune cells, which affects the onset of cancer pain and the regulation of the proteins involved in the invasion process, we introduce a novel cancer-induced neuropathic pain model. In this model, we directly inoculated the tumor cells within the neuronal sheath, which allowed a direct contact with the neuronal fibers from the time of injection. E interference of tissue-resident immune cells does not allow a direct contact with nerve fibres which affects the tumor microenvironment and the invasion process. A novel and a promising model of cancer-induced neuropathy was established, and the role of TRPA1 and CGRP in pain transduction was examined

Methods

Results

Discussion

Conclusion