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.