Searching for analgesic drug candidates alleviating oxaliplatin-induced cold hypersensitivity in mice

Oxaliplatin is a third-generation, platinum-based derivative used to treat advanced colorectal cancer. Within the patient population on oxaliplatin therapy, a lower incidence of hematological adverse effects and gastrointestinal toxicity is noted, but severe neuropathic pain episodes characterized by increased cold and tactile hypersensitivity are present in ~95% of patients. This drug is also used to induce a rodent model of chemotherapy-induced peripheral neuropathy (CIPN)-related neuropathic pain which is widely used in the search for novel therapies for CIPN prevention and treatment. This paper provides a step-by-step, detailed description of the prevention and intervention protocols used in our laboratory for the assessment of oxaliplatin-induced cold allodynia in mice. To establish cold sensitivity in mice, the cold plate test was used. Latencies to pain reaction in response to cold stimulus (2.5°C) for vehicle-treated non-neuropathic mice, vehicle-treated mice injected with oxaliplatin (neuropathic control), and oxaliplatin-treated mice treated additionally with duloxetine are compared. Duloxetine is a serotonin/noradrenaline reuptake inhibitor which was found to produce significant pain relief in patients with CIPN symptoms. In our present study, duloxetine administered intraperitoneally at the dose of 30 mg/kg served as a model antiallodynic drug which attenuated or partially prevented cold allodynia caused by oxaliplatin.