Acute cold allodynia induced by oxaliplatin is attenuated by amitriptyline

Abstract

Oxaliplatin is a third-generation, platinum-based antitumor drug used to treat colorectal cancer. Since its main adverse effect is neuropathic pain resulting from chemotherapy‑induced peripheral neuropathy (CIPN), this drug is used to study the neurobiology of CIPN in rodents and to search for analgesics that could attenuate neuropathic pain symptoms - cold and tactile allodynia that develop in most of the oxaliplatin‑treated subjects. In this research, testing across various temperatures, we assessed the cold reactivity threshold of albino Swiss mice treated with oxaliplatin. We also investigated if amitriptyline, a tricyclic antidepressant drug and a sodium channel inhibitor, could attenuate cold allodynia caused by this chemotherapeutic drug. Cold allodynia was induced using a single intraperitoneal dose of oxaliplatin. In the cold plate test while testing various temperatures the pain sensitivity threshold was assessed at different time-points after oxaliplatin (late‑phase allodynia). Antiallodynic activity of intraperitoneal amitriptyline was assessed for doses of 1, 2.5 and 10 mg/kg. A statistically significant decrease in latency time to pain reaction was detected for all temperatures applied, but the earliest response (i.e., 2 h post‑injection) was noted at 2.5°C. In all experimental groups early‑phase cold allodynia was fully developed 3 h after oxaliplatin injection and it was maintained until the end of the observation period (7 days). Early‑phase cold allodynia induced by oxaliplatin can be effectively attenuated by amitriptyline.