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Searching for analgesic drug candidates alleviating oxaliplatin‐induced cold hypersensitivity in mice
Author(s) -
Sałat Kinga,
Furgała Anna,
MalikowskaRacia Natalia
Publication year - 2019
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13507
Subject(s) - oxaliplatin , medicine , neuropathic pain , allodynia , duloxetine , pharmacology , analgesic , adverse effect , anesthesia , drug , peripheral neuropathy , colorectal cancer , hyperalgesia , nociception , cancer , receptor , endocrinology , alternative medicine , pathology , diabetes mellitus
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.