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The beneficial effects of isothiocyanate-based compounds, as well as their safety, have been shown in neuropathological disorders, such as neuropathic pain. Aim of the present work was to study the efficacy of the glucosinolate glucoraphanin (GRA) and the derived isothiocyanate sulforaphane (SFN), secondary metabolites occurring exclusively in Brassicales, on chemotherapy-induced neuropathic pain. Mice were repeatedly treated with oxaliplatin (2.4 mg kg ip) for 14 days to induce neuropathic pain. GRA and SFN effects were evaluated after a single administration on Day 15 or after a daily repeated oral and subcutaneous treatment starting from the first day of oxaliplatin injection until the 14 day. Single subcutaneous and oral administrations of GRA (4.43-119.79 μmol kg ) or SFN (1.33-13.31 μmol kg ) reduced neuropathic pain in a dose-dependent manner. The repeated administration of GRA and SFN (respectively 13.31 and 4.43 μmol kg ) prevented the chemotherapy-induced neuropathy. The co-administration of GRA and SFN in mixture with the H S binding molecule, haemoglobin, abolished their pain-relieving effect, which was also reverted by pretreating the animals with the selective blocker of Kv7 potassium channels, XE991. GRA and SFN reduce neuropathic pain by releasing H S and modulating Kv7 channels and show a protective effect on the chemotherapy-induced neuropathy.

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