Figure 2. Up-regulation of GABA_B2 receptor expression in small diameter DRG neurons after chronic oxycodone treatment.

A–C: Immunofluorescent staining showing GABA_B2 receptor immunoreactive neurons (arrowheads) in representative vincristine-saline (A), vincristine-morphine, (B) and vincristine-oxycodone (C) treated animals. Scale bars  = 50 μm. D: Relative expression of Gabbr2 in the DRG of vincristine-treated rats determined by qPCR. The results validate the up-regulation of the Gabbr2 gene observed by DNA microarray in the vincristine-oxycodone treated rat, as compared to a vincristine-morphine treated rat. Data obtained from vincristine-treated rats were normalized to control rat data (n = 4 per group; *p<0.05 between vincristine-oxycodone treated rats and vincristine-morphine treated rats). Data were expressed as mean ± SEM. E: Histogram showing the size distribution frequency of GABA_B2 receptor expression in the DRG for all vincristine groups. Note that the size distribution frequency was identical in the three groups studied. F: Percentage of GABA_B2 receptor-positive neurons in the three animal groups. Oxycodone induced an increased percentage of GABA_B2 receptor-positive neurons as compared to morphine treatment. G: Analysis of the mean intensity of GABA_B2 receptor staining in the three vincristine-treated animals. Oxycodone induced a 53% increase in GABA_B2 receptor staining in vincristine-oxycodone treated rats as compared to vincristine-morphine treated rats, and an 84% increase as compared to vincristine-saline treated rats. (n = 4 vincristine-morphine treated rats, n = 4 vincristine-oxycodone treated rats, and n = 4 vincristine-saline treated rats) *p<0.05 between vincristine-oxycodone treated rats and vincristine-morphine treated rats; #p<0.05 between vincristine-oxycodone treated rats and vincristine-saline treated rats. Data are expressed as mean ± SEM.