Details

Autor(en) / Beteiligte

• Sałat, Kinga
• Furgała, Anna
• Malikowska‐Racia, Natalia

Titel

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

Ist Teil von

• Chemical biology & drug design, 2019-06, Vol.93 (6), p.1061-1072

Ort / Verlag

England

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Wiley Online Library Journals【キャンパス外アクセス可】

Beschreibungen/Notizen

• 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. Oxaliplatin is widely used to induce a rodent model of chemotherapy‐induced neuropathic pain. This pain model is useful in the search for novel analgesics. In this paper, we present the protocol used in our laboratory for the assessment of cold allodynia caused by oxaliplatin and we show antiallodynic efficacy of duloxetine in this mouse model of neuropathic pain.