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The Analgesic Effect of Venlafaxine and Its Mechanism on Oxaliplatin-Induced Neuropathic Pain in Mice
oleh: Daxian Li, Ji Hwan Lee, Chang Won Choi, Jaihwan Kim, Sun Kwang Kim, Woojin Kim
Format: | Article |
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Diterbitkan: | MDPI AG 2019-04-01 |
Deskripsi
The analgesic effect of venlafaxine (VLX), which is a selective serotonin and noradrenaline reuptake inhibitor (SNRI), has been observed on oxaliplatin-induced neuropathic pain in mice. Significant allodynia was shown after oxaliplatin treatment (6 mg/kg, i.p.); acetone and von Frey hair tests were used to assess cold and mechanical allodynia, respectively. Intraperitoneal administration of VLX at 40 and 60 mg/kg, but not 10 mg/kg, significantly alleviated these allodynia. Noradrenaline depletion by pretreatment of <i>N</i>-(2-Chloroethyl)-<i>N</i>-ethyl-2-bromobenzylamine (DSP-4, 50 mg/kg, i.p.) blocked the relieving effect of VLX (40 mg/kg, i.p.) on cold and mechanical allodynia. However, serotonin depletion by three consecutive pretreatments of para-chlorophenylalanine (PCPA, 150 mg/kg/day, i.p.) only blocked the effect of VLX on mechanical allodynia. In cold allodynia, the α<sub>2</sub>-adrenergic antagonist idazoxan (10 μg, i.t.), but not the α<sub>1</sub>-adrenergic antagonist prazosin (10 μg, i.t.), abolished VLX-induced analgesia. Furthermore, idazoxan and 5-HT<sub>3</sub> receptor antagonist bemesetron (MDL-72222, 15 μg, i.t.), but not prazosin or mixed 5-HT<sub>1, 2</sub> receptor antagonist methysergide (10 μg, i.t.), abolished VLX-induced analgesia in mechanical allodynia. In conclusion, 40 mg/kg of VLX treatment has a potent relieving effect against oxaliplatin-induced neuropathic pain, and α<sub>2</sub>-adrenergic receptor, and both α<sub>2</sub>-adrenergic and 5-HT<sub>3</sub> receptors are involved in this effect of VLX on cold and mechanical allodynia, respectively.