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Anesthesiology. 2010 Mar;112(3):696-710. doi: 10.1097/ALN.0b013e3181cd7920.

Spinal 5-HT7 receptors play an important role in the antinociceptive and antihyperalgesic effects of tramadol and its metabolite, O-Desmethyltramadol, via activation of descending serotonergic pathways.

Author information

1
Department of Anesthesiology and Reanimation, Gulhane Military Academy of Medicine, Ankara, Turkey.

Abstract

BACKGROUND:

Tramadol is an analgesic drug, and its mechanism of action is believed to be mediated by the mu-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 microg) and SB-258719 (20 microg) blocked both tramadol- and M1-induced antinociceptive and antihyperalgesic effects. Ketanserin (20 mumicrog) and ondansetron (20 microg) 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.

PMID:
20179508
DOI:
10.1097/ALN.0b013e3181cd7920
[Indexed for MEDLINE]

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