Low doses of fentanyl block central sensitization in the rat spinal cord in vivo

Abstract

Background: mu-Opioid receptor agonists are strong analgesics. However, their usefulness for preemptive analgesia is controversial. The authors tested antinociceptive and preemptive properties of fentanyl as a mu-opioid receptor agonist in a model of spinal nociception in vivo.

Methods: C fiber-evoked potentials were recorded in the superficial laminae I-II of the rat lumbar spinal cord with glass microelectrodes in response to electrical stimulation of the sciatic nerve. High-frequency stimulation was applied on the sciatic nerve to induce long-term potentiation of C fiber-evoked field potentials, a form of central sensitization. To test the effect of fentanyl on acute nociception, fentanyl was infused intravenously at increasing doses (6-192 microg.kg(-1).h(-1)). One hour after start of infusion, high-frequency stimulation was applied to evaluate effects of fentanyl on the induction of long-term potentiation.

Results: In the absence of fentanyl, high-frequency stimulation potentiated C fiber-evoked field potentials to 149 +/-12% of controls (mean +/-SEM; n = 6) for at least 1 h. Increasing doses of fentanyl led to a significant reduction of C fiber-evoked potentials in a dose-dependent manner. The induction of long-term potentiation was blocked by low doses of fentanyl (infusion 12-48 microg.kg(1).h(-1)). At high doses, fentanyl did not block the induction of long-term potentiation (infusion 96-192 microg.kg(-1).h(-1)).

Conclusions: : Low doses of fentanyl block the synaptic form of central sensitization in the rat spinal cord in vivo, but higher doses do not have this effect.