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

  title={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={Omer Yanarateş and Ahmet Bulent Dogrul and Vedat Yıldırım and Altan Şahin and Ali Sızlan and Melik Seyrek and {\"O}zg{\"u}r Akg{\"u}l and Orhan Kozak and Ercan Kurt and Ulku Aypar},
Background:Tramadol is an analgesic drug, and its mechanism of action is believed to be mediated by the &mgr;-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… 
Different role of spinal 5-HT(hydroxytryptamine)7 receptors and descending serotonergic modulation in inflammatory pain induced in formalin and carrageenan rat models.
Spinal 5-HT7R plays a significant inhibitory role in descending serotonergic modulation in pain induced by formalin but not carrageenan, with facilitatory and inhibitory effects, respectively.
Expression of the spinal 5-HT7 receptor and p-ERK pathway in the carrageenan inflammatory pain of rats
The expression of the spinal 5- HT7R is not altered by peripheral inflammation with carrageenan, suggesting that the lack of antinociceptive effect of the 5-HT7R activation is partly attributable to the absence of changes in the expression of this receptor in the spinal cord.
Descending serotonergic and noradrenergic systems do not regulate the antipruritic effects of cannabinoids*
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Differential role of 5-HT1A and 5-HT1B receptors on the antinociceptive and antidepressant effect of tramadol in mice
The results suggest the involvement of the 5- HT1A autoreceptors from the raphe nuclei and spinal 5-HT1A receptors in the antinociceptive effect and the blockade of the antidepressant-like effect of tramadol.
Actions of tramadol, its enantiomers and principal metabolite, O-desmethyltramadol, on serotonin (5-HT) efflux and uptake in the rat dorsal raphe nucleus.
Activity of (+/-)-tramadol and the (+)-enantiomer, at clinically relevant concentrations, may help to explain the antinociceptive efficacy of tramadol despite weak mu opioid receptor affinity and adds to evidence that tramadl exerts actions on central monoaminergic systems that may contribute to its analgesic effect.
Interaction of the central analgesic, tramadol, with the uptake and release of 5‐hydroxytryptamine in the rat brain in vitro
An intact uptake system is necessary for the enhancement of extraneuronal 5‐HT concentrations by tramadol indicating an intraneuronal site of action.
Ondansetron Inhibits the Analgesic Effects of Tramadol: A Possible 5-HT3 Spinal Receptor Involvement in Acute Pain in Humans
It is concluded that ondansetron reduced the overall analgesic effect of tramadol, probably blocking spinal 5-HT3 receptors.
Mu opioid receptor-dependent and independent components in effects of tramadol
Influence of tramadol on neurotransmitter systems of the rat brain.
The results indicate that tramadol enhances DA turnover via an opioid mechanism and closely resembles that of NA and 5-HT uptake inhibitors.
The antinociceptive effect of tramadol in the formalin test is mediated by the serotonergic component.