Inhibition of FAAH reverses spinal LTP
-
Guro S. Eriksen
, Line M. Jacobsen , Linda M. Pedersen and Johannes Gjerstad
Objectives
Fatty-acid amide hydrolase (FAAH) is an enzyme that metabolizes several endocannabinoids and fatty acid amides important for human pain sensitivity. Here we examine how reduced FAAH activity affects maintenance of spinal long-term potentiation (LTP) and spinal expression of the transcription factor Zif.
Methods
Dorsal horn field potential recordings were performed in urethane anaesthetized SPD rats. LTP was induced by high frequency stimulation (HFS) conditioning applied to the sciatic nerve. To inhibit the enzymatic activity of FAAH, URB 597 was administered (1 mg/kg i.v.). Gene expression of the transcription factor Zif was examined by real time RT-PCR.
Results
A clear LTP was observed after HFS conditioning. The expression of LTP was, however, significantly reduced after i.v. administration of the FAAH inhibitor URB 597. A significant increase in the gene expression level of Zif was demonstrated in the ipsilateral dorsal horn after HFS compared to the corresponding control.
Conclusion
Our results demonstrated that inhibition of FAAH partly reverses spinal LTP. While the HFS conditioning caused a clear increase in Zif gene expression in the ipsilateral dorsal horn, HFS in combination with the FAAH inhibitor did not. We conclude that FAAH may be important for the neuronal mechanisms underlying maintenance of spinal LTP. Whether or not the increased gene expression of Zif is important for these mechanisms remains to be investigated.
© 2010 Scandinavian Association for the Study of Pain
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