Role of Transient Receptor Potential Ankyrin 1 (TRPA1) channel in anticancer drugs-induced peripheral neuropathy and pain

The work described in this thesis is aimed at defining the role of TRPA1 in several painful states induced by the chemotherapeutic agents paclitaxel, bortezomib and third-generation aromatase inhibitors. To this purpose both in vitro and in vivo assays have been used. Calcium imaging experiments were performed in order to explore whether paclitaxel, bortezomib and third-generation aromatase inhibitors were able to directly gate the TRPA1 channel evoking painful states. Furthermore, several animal models of chemotherapy-evoked painful side effects were developed and the involvement of TRPA1 was investigated through the use of Trpa1+/+ and Trpa1-/- mice or via the administration of TRPA1 selective antagonist.