Searching for analgesic drug candidates alleviating oxaliplatin-induced cold hypersensitivity in mice.
Kinga SałatAnna FurgałaNatalia Malikowska-RaciaPublished in: Chemical biology & drug design (2019)
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.
Keyphrases
- neuropathic pain
- spinal cord
- spinal cord injury
- high fat diet induced
- drug induced
- chemotherapy induced
- newly diagnosed
- randomized controlled trial
- emergency department
- ejection fraction
- wild type
- high glucose
- risk factors
- type diabetes
- metabolic syndrome
- oxidative stress
- endothelial cells
- skeletal muscle
- depressive symptoms
- adipose tissue
- end stage renal disease
- cell therapy
- electronic health record