Non-linear morphine-induced depression of spinal excitation following long-term potentiation of C fibre-evoked spinal field potentials.

Reduced efficacy of opioid analgesics in some abnormal pain states is a common clinical observation. We tested whether the depressing effect of spinally administered morphine (MOR) on C fibre-evoked spinal field potentials is diminished during long-term potentiation (LTP) induced in the spinal dorsal horn by high-frequency stimulation (HFS). MOR distinctly reduced evoked field potentials 2 h after LTP induction, yet MOR doses suppressing spinal responses in control rats (500 microM) failed to achieve so in HFS-receiving rats. However, HFS and MOR administration at the 0.01-0.1 mM range were found to interact positively as independent variables, suggesting that LTP induction may trigger an endogenous factor enhancing the effectiveness of spinally applied MOR. The present findings suggest that LTP-like, long-lasting enhancement of synaptic strength in the spinal dorsal horn can contribute to increasing MOR doses required for antinociception in some forms of abnormal pain.