Nayebi A R, Hassanpour M, Rezazadeh H
Department of Pharmacology, Faculty of Pharmacy, Tabrize University of Medical Sciences, Iran.
J Pharm Pharmacol. 2001 Feb;53(2):219-25. doi: 10.1211/0022357011775235.
Serotonergic systems are involved in the central regulation of nociceptive sensitivity. Fluoxetine, a selective inhibitor of the reuptake of serotonin (5-hydroxytryptamine, 5-HT), was administered orally (0.16, 0.32, 0.8 mg kg(-1) daily for 7 days), intraperitoneally (0.04, 0.08, 0.16 mg kg(-1) day(-1) for 7 days and a single dose of 0.32 mg kg(-1)) and intracerebroventricularly (10 microg/rat) to rats and nociceptive sensitivity was evaluated using the formalin test (50 microL of 2.5% formalin injected subcutaneously). The effect of fluoxetine was also studied in the presence of 5,7-dihydroxytryptamine creatinine sulfate (5,7-DHT) and after co-administration with morphine. Oral (0.8 mg kg(-1)), intraperitoneal (0.16 and 0.32 mg kg(-1)) and intracerebroventricular (10 microg/rat) fluoxetine induced antinociception in the late phase of the formalin test. Furthermore, intrathecal administration of 5-HT (100 microg/rat) induced an analgesic effect. The analgesic effect of fluoxetine (0.16 and 0.32 mg kg(-1), i.p.) and 5-HT (100 microg/rat, i.t.) was abolished by pre-treatment with 5,7-DHT (100 microg/rat, i.t.). In addition, the analgesic effect of 5-HT (100 microg/rat, i.t.) was decreased by pre-treatment with naloxone (2 mg kg(-1), i.p.). Morphine (5 mg kg(-1), i.p.) induced analgesia that was increased by fluoxetine (0.32 mg kg(-1), i.p.). These results suggest that fluoxetine has an antinociceptive effect in tonic inflammatory pain through functional alteration of the serotonergic system and also potentiates the analgesic effect of morphine.
5-羟色胺能系统参与伤害性感受敏感性的中枢调节。氟西汀是一种5-羟色胺（5-羟色胺，5-HT）再摄取的选择性抑制剂，分别以口服（每日0.16、0.32、0.8 mg·kg⁻¹，共7天）、腹腔注射（每日0.04、0.08、0.16 mg·kg⁻¹，共7天，单次剂量0.32 mg·kg⁻¹）和脑室内注射（10 μg/只大鼠）的方式给予大鼠，并用福尔马林试验（皮下注射50 μL 2.5%福尔马林）评估伤害性感受敏感性。还研究了在存在5,7-二羟基色胺硫酸肌酐（5,7-DHT）的情况下以及与吗啡联合给药后氟西汀的作用。口服（0.8 mg·kg⁻¹）、腹腔注射（0.16和0.32 mg·kg⁻¹）和脑室内注射（10 μg/只大鼠）氟西汀在福尔马林试验的后期诱导产生抗伤害感受作用。此外，鞘内注射5-HT（100 μg/只大鼠）可产生镇痛作用。预先用5,7-DHT（100 μg/只大鼠，鞘内注射）处理可消除氟西汀（0.16和0.32 mg·kg⁻¹，腹腔注射）和5-HT（100 μg/只大鼠，鞘内注射）的镇痛作用。此外，预先用纳洛酮（2 mg·kg⁻¹，腹腔注射）处理可降低5-HT（100 μg/只大鼠，鞘内注射）的镇痛作用。吗啡（5 mg·kg⁻¹，腹腔注射）诱导的镇痛作用可被氟西汀（0.32 mg·kg⁻¹，腹腔注射）增强。这些结果表明，氟西汀通过5-羟色胺能系统的功能改变对紧张性炎性疼痛具有抗伤害感受作用，并且还可增强吗啡的镇痛作用。
