Akademik Veri Yönetim Sistemi
Anesthesiology, cilt.112, sa.3, ss.696-710, 2010 (SCI-Expanded)
Background: Tramadol is an analgesic drug, and its mechanism of action is believed to be mediated by the μ-opioid receptor. A further action of tramadol has been identified as blocking the reuptake of serotonin (5-HT). One of the most recently identified subtypes of 5-HT receptor is the 5-HT7 receptor. Thus, the authors aimed to examine the potential role of serotonergic descending bulbospinal pathways and spinal 5-HT7 receptors compared with that of the 5-HT2A and 5-HT3 receptors in the antinociceptive and antihyperalgesic effects of tramadol and its major active metabolite O-desmethyltramadol (M1) on phasic and postoperative pain models. Methods: Nociception was assessed by the radiant heat tail-flick and plantar incision test in male Balb-C mice (25-30 g). The serotonergic pathways were lesioned with an intrathecal injection of 5,7-dihydroxytryptamine. The selective 5-HT7, 5-HT2, and 5-HT3 antagonists; SB-269970 and SB-258719; ketanserin and ondansetron were given intrathecally. Results: Systemically administered tramadol and M1 produced antinociceptive and antihyperalgesic effects. The antinociceptive effects of both tramadol and M1 were significantly diminished in 5-HT-lesioned mice. Intrathecal injection of SB-269970 (10 μg) and SB-258719 (20 μg) blocked both tramadol-and M1-induced antinociceptive and antihyperalgesic effects. Ketanserin (20 μg) and ondansetron (20 μg) were unable to reverse the antinociceptive and antihyperalgesic effects of tramadol and M1. Conclusions: These findings suggest that the descending serotonergic pathways and spinal 5-HT7 receptors play a crucial role in the antinociceptive and antihyperalgesic effects of tramadol and M1. Copyright © 2010, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins.