Figure 5.
Tolerance evaluation of DN‐9 and morphine in different pain models. Antinociceptive effects of repeated administration of DN‐9 (9.48 μmol·kg−1, s.c.) and morphine (31.08 μmol·kg−1, s.c.) on acute (a), inflammatory (b), and neuropathic pain models [(c) anti‐allodynia; (d) anti‐hyperalgesia]. To evaluate the role of NPFF receptor on the tolerance development of DN‐9, RF9 was administrated prior to DN‐9 daily treatment in acute (a) and inflammatory (b) pain models. * P < .05, significantly different from the nociceptive latency on Day 1; one‐way ANOVA followed by Tukey's HSD post hoc test. To evaluate the effects of DN‐9 on the nociceptive latency in mice tolerance to morphine (31.08 μmol·kg−1, once daily for 7 days), DN‐9 (9.48 μmol·kg−1) was s.c. administered on Day 8 in inflammatory (b) and neuropathic (c,d) pain models. Each data point represents the mean ± SEM, n = 7–8 mice per group. # P < .05, indicates significant difference between latencies on Day 7 and Day 8; paired t test. (e,f) Effects of chronic DN‐9 and morphine administration on the expression of microglial cells in spinal cord. Each data point represents the mean ± SEM, n = 5, 5–6 images per animal. * P < .05, significantly different from saline group; one‐way ANOVA followed by Bonferroni's post hoc test. Scale bar equals 50 μm