5-HT1A receptors mediate the analgesic effect of rosavin in a mouse model of oxaliplatin-induced peripheral neuropathic pain
Daxian Li1,5, Sangwon Park2, Kyungjoon Lee3, Dae Sik Jang4, and Sun Kwang Kim1,2,3,*
1Department of Physiology, College of Korean Medicine, Kyung Hee University, Departments of 2Korean Medicine, 3East-West Medicine, 4Life and Nanopharmaceutical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea, 5Department of Anesthesiology, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China
Oxaliplatin, a third-generation platinum derivative, is the mainstay of current antineoplastic medications for advanced colorectal cancer therapy. However, peripheral neuropathic complications, especially cold allodynia, undermine the lifeprolonging outcome of this anti-cancer agent. Rosavin, a phenylpropanoid derived originally from Rhodiola rosea, exhibits a wide range of therapeutic properties. The present study explored whether and how rosavin alleviates oxaliplatin-induced cold hypersensitivity in mice. In the acetone drop test, cold allodynia behavior was observed from days 3 to 5 after a single injection of oxaliplatin (6 mg/kg, i.p.). Cold allodynia was significantly attenuated following rosavin treatment (10 mg/kg, i.p.). Specific endogenous 5-HT depletion by three consecutive pretreatments with parachlorophenylalanine (150 mg/kg/day, i.p.) abolished the analgesic action of rosavin; this effect was not observed following pretreatment with naloxone (opioid receptor antagonist, 10 mg/kg, i.p.). Furthermore, 5-HT1A receptor antagonist WAY-100635 (0.16 mg/kg, i.p.), but not 5-HT3 receptor antagonist MDL-72222 (1 mg/kg, i.p.), blocked rosavin-induced analgesia. These results suggest that rosavin may provide a novel approach to alleviate oxaliplatin-induced cold allodynia by recruiting the activity of 5-HT1A receptors.