Figure 5.

Immediate-onset, descending facilitation requires activation of extraspinal MORs and spinal 5-HT₃Rs. Areas of C-fiber-evoked field potentials were normalized to predrug values (dotted line) and plotted against time (minutes). A, Intravenous infusion of the opioid receptor antagonist naloxone (hatched bar; 100 mg·kg⁻¹·h⁻¹) blocked depression induced by intravenous fentanyl (black bar; dosing as in Fig. 1B) as well as opioid-induced enhancement of synaptic transmission. B, Spinal superfusion with the 5-HT₃R antagonist granisetron and MOR antagonist CTOP (white bar; 1 mm and 10 μm, respectively) abolished immediate-onset, descending facilitation induced by intravenous fentanyl (black bar). C, Granisetron was applied to the spinal cord dorsum (top white bar; 1 mm). Precipitated withdrawal from intravenous fentanyl with spinal CTOP (bottom white bar; 10 μm) induced withdrawal LTP.