Previous studies indicate that inhibition of fatty acid amide hydrolase (FAAH) activity may result in accumulation of endocannabinoids both in the brain and the spinal cord. Furthermore, it has been suggested that the events following inhibition of FAAH activity interact with opioid signaling important for nociceptive modulation.
Therefore, electrophysiological extracellular field potential recordings were performed to investigate if inhibition of FAAH activity affects nociceptive signaling in the spinal cord and to examine a possible interaction between FAAH inhibition and opioid signaling. A single stimulus was applied to the sciatic nerve of anaesthetised rats, and as a measurement of nociceptive response, the C-fibre response was quantified. To inhibit the enzymatic activity of FAAH and the opioid receptors, URB597 (1.0 mg/kg i.v.) and naloxone (0.1 μg/μl i.th.) were administred, respectively. Quantitative real time RT-PCR was used to explore if FAAH inhibition is associated with changes in spinal dorsal horn gene expression of the genes encoding Zif and iNOS.
The field potential recordings demonstrated that the C-fibre response was reduced after inhibition of FAAH by URB597, and that this inhibition was reversed by blocking of the opioid receptors by naloxone. The gene expression analyses did not show any significant change in the expression of Zif and iNOS following FAAH inhibition.
The present data suggest that inhibition of the FAAH enzyme reduces the spinal nociceptive responses and that the underlying mechanism may involve activation of opioid receptors and/or intracellular pathways.