Chemotherapy-induced neuropathy: involvement of the alpha7 nAChR subtype

The limiting side effect of the chemotherapeutic agent oxaliplatin is its neurotoxicity, which promotes a neuropathic syndrome. In a rat model of oxaliplatin-induced neuropathy (2.4 mgkg-1 intraperitoneally, daily injected for 21 days), a dramatic decrease of the alpha7 nAChR protein expression levels was highlighted in the peripheral as well as central nervous system. The repeated treatment with the eutomer of the new alpha7 nAChR agonist ICH-3 (30 mgkg-1 p. os, daily administered for 21 days, starting from the first oxaliplatin injection) prevented mechanical hyperalgesia, mechanical and thermal allodynia, and improved motor coordination. Western blot analysis revealed that this treatment with the agonist significantly counteracted the decrease of alpha7 protein levels. Further ex vivo analysis of the nervous system evidenced a neuroprotective effect for ICH-3. On the whole, these results strongly suggest the pivotal role of alpha7 nAChRs in neuroprotection during chemotherapy-induced neuropathy.