Figure 4.

Depletion of descending NA and 5-HT levels almost abolishes the analgesic effects of supraspinally administered taltirelin on mechanical and thermal nociception, respectively. To deplete NA (a) or 5-HT (b), 6-OHDA or PCPA was injected intracisternally once or administered i.p. for 5 consecutive days, respectively. Taltirelin hydrate (tal, 0.1 and 0.3 μg, i.c.v.) was administered at time zero. Each point represents the mean (±s.e.m.) result from six mice. Ordinates: mean normalized tail flick latencies (tail flick test; left) and nociceptive thresholds (tail pressure test; right). Abscissae: time in minutes after taltirelin application. The asterisks indicate data points for which a significant difference between the control and taltirelin-treated groups was observed, as determined by two-tailed non-parametric Bonferroni-type multiple comparisons following the Kruskal–Wallis test (two comparisons in three groups, ^*P<0.05). Pretreatment with vehicle (ascorbic acid in (a) and CMC in (b)) alone did not affect the antinociceptive effects of taltirelin hydrate (0.3 μg, i.c.v.), as shown superimposed in the graphs (n=6, clear squares).