Korean J Physiol Pharmacol.  2021 Sep;25(5):489-494. 10.4196/kjpp.2021.25.5.489.

5-HT 1A receptors mediate the analgesic effect of rosavin in a mouse model of oxaliplatin-induced peripheral neuropathic pain

Affiliations
  • 1Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea.
  • 2Department of Anesthesiology, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China.
  • 3Department of Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea.
  • 4Department of East-West Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea.
  • 5Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea.

Abstract

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.

Keyword

Cold allodynia; Oxaliplatin; Peripheral neuropathy; Rosavin; Serotonergic
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