pISSN 1226-4512 eISSN 2093-3827


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Original Article

Korean J Physiol Pharmacol 2021; 25(5): 489-494

Published online September 1, 2021 https://doi.org/10.4196/kjpp.2021.25.5.489

Copyright © Korean J Physiol Pharmacol.

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

Correspondence to:Sun Kwang Kim
E-mail: skkim77@khu.ac.kr

Received: April 19, 2021; Revised: June 8, 2021; Accepted: June 21, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © Korean J Physiol Pharmacol, pISSN 1226-4512, eISSN 2093-3827


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.

Keywords: Cold allodynia, Oxaliplatin, Peripheral neuropathy, Rosavin, Serotonergic