Figure 2.

Effects of adrenoceptor or 5-HT receptor antagonists on the inhibitory effect of milnacipran (Mil) on the C-fibre-evoked field potentials (FPs) following the establishment of long-term potentiation (LTP) in naïve animals. FPs in the spinal dorsal horn were elicited by electrical stimulation of the sciatic nerve fibres at 1 min intervals in anaesthetized naïve adult rats. LTP of C-fibre-evoked FPs was induced by high-frequency stimulation (HFS; 0.5 ms duration, 40–45 V, 100 Hz, given in two trains of 1 s duration at 20 s intervals; arrowhead) of the sciatic nerve fibres. Each area of C-fibre-evoked FPs was normalized to the mean of 60 consecutive responses obtained prior to HFS (–60 to 0 min in the graph) and five consecutive responses were averaged. (A) Yohimbine (Yoh; n= 4), idazoxan (Ida; n= 3) or methysergide (Met; n= 4) was administered spinally 60 min after HFS (arrow), when the enhancement of C-fibre-evoked FPs by HFS was fully established. (B) Yohimbine (n= 5), idazoxan (n= 5) or methysergide (n= 6) was administered spinally 45 min after HFS. Yohimbine, idazoxan or methysergide plus milnacipran were administered spinally 60 min after HFS. (C) The inhibitory effects of 10 µM milnacipran on the C-fibre-evoked FPs with or without yohimbine, idazoxan or methysergide. The % inhibition of C-fibre-evoked FPs was calculated using the mean area of 30 consecutive FPs during 90–120 min following the vehicle or milnacipran administration (averaged at 150–180 min after HFS) in comparison to the pre-drug values (averaged at 30–60 min after HFS). The values in vehicle and milnacipran groups are from Figure 1. Data shown are means ± SEM. *P < 0.05; **P < 0.01, significantly different as indicated.