Behavior and electrophysiology studies of the peripheral neuropathy induced by individual and co-administration of paclitaxel and oxaliplatin in rat

• Published in: Life sciences (1973) 2021-07, Vol.277, p.119397-119397, Article 119397
• Main Authors: Paniagua, N., Sánchez-Robles, E.M., Bagues, A., Martín-Fontelles, M.I., Goicoechea, C., Girón, R.
• Format: Article
• Language: English
• Subjects: Animals; Anticancer properties; Antitumor activity; Antitumor agents; Aδ-fibers; Cancer; Cancer therapies; Chemotherapy; Chemotherapy peripheral neuropathy; Drugs; Electrophysiology; Fibers; Hypersensitivity; Orofacial pain; Oxaliplatin; Paclitaxel; Pain perception; Peripheral neuropathy; Platinum; Platinum compounds; Saphenous nerve; Sensory neurons; Side effects; Skin; Taxanes
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2021.119397

Antitumor agents, as taxanes and platinum compounds, induce peripheral neuropathies which can hamper their use for cancer treatment. The study of chemotherapy-induced neuropathies in humans is difficult because of ethical reasons, differences among administration protocols and intrinsic characteristics of patients. The aim of the present study is to compare the neuropathic signs induced by individual or combined administration of paclitaxel and oxaliplatin. Oxaliplatin and paclitaxel were administered individually and combined to induce peripheral neuropathy in rats, sensory neuropathic signs were assessed in the hind limbs and orofacial area. The in vitro skin-saphenous nerve preparation was used to record the axonal activity of Aδ sensory neurons. Animals treated with the combination developed mechanical allodynia in the paws and muscular hyperalgesia in the orofacial area, which was similar to that in animals treated with monotherapy, the latter also developed cold allodynia in the paws. Aδ-fibers of the rats treated with the combination were hyperexcited and presented hypersensitivity to pressure stimulation of the innervated skin, also similar to that recorded in the fibers of the animals treated with monotherapy. Our work objectively demonstrates that the combination of a platinum compound with a taxane does not worsen the development of sensorial neuropathies in rats, which is an interesting data to take into account when the combination of antitumor drugs is necessary. Co-administration of antitumor drugs is more effective in cancer treatment without increasing the risk of the disabling neuropathic side effects. •Oxaliplatin or paclitaxel induce a chronic painful peripheral neuropathy in the hind limbs and orofacial region in rats.•When both antitumorals are co-administered, the peripheral neuropathy is not worse than when individually administered.•In the paws, impaired mechanical perception correlates with a hyperexcited state of the Aδ-fibers of the saphenous nerve.•The risk of inducing a disabling neuropathy does not increase when the combination is needed to improve the effectiveness.