(a)
(b)
Figure 2: Cold stimulation evokes brain activation in oxaliplatin-treated macaques, which is attenuated with duloxetine. Before and three days after oxaliplatin treatment, brain activation was visualized with a 3.0 T Philips Healthcare MRI system in propofol-sedated macaques [42]. Alternating temperatures (cold, 10°C and neutral, 37°C) were applied to the tail for 30 sec. each with a 30 sec. interval without stimulation. (a) Cold stimulation in oxaliplatin-treated macaques activated secondary somatosensory cortex (SII) and insula (Ins). Activation in the left cerebellum (Cb) following cold stimulation was also observed. Contrast was defined as (10°C stimulation −37°C stimulation after oxaliplatin treatment)–(10°C stimulation −37°C stimulation before oxaliplatin treatment; “intact”). Peak voxels Z values greater than 3.0 were (uncorrected for multiple comparisons, one-tailed). Coronal sections of oxaliplatin-treated macaques averaged from four macaques. Sections arranged from rostral (upper left) to caudal (lower right) and spaced 2 mm apart. R, right; L, left. (b) Duloxetine suppressed cold-induced activation in SII and Ins in oxaliplatin-treated macaques. However, activation in Cb was still present following duloxetine treatment. Three days after oxaliplatin treatment, macaques were dosed with duloxetine (p.o. 30 mg/kg) and cold-evoked brain activation was measured one hour following duloxetine treatment. The effect of duloxetine treatment on cold-evoked brain activation in oxaliplatin-treated macaques (“after duloxetine treatment (Post-oxaliplatin)”) was compared to cold-evoked brain activation before oxaliplatin treatment (“intact”). No significant activation in SII and Ins was observed following duloxetine treatment (). Thus, the lack of activity in SII and Ins following duloxetine administration in oxaliplatin-treated macaques was similar to that of macaques prior to oxaliplatin treatment. (An additional analysis was performed comparing cold-evoked SII and Ins activation after and before duloxetine treatment in oxaliplatin-treated macaques (data not shown, [42]). Activation in SII and Ins following duloxetine treatment was significantly suppressed—the difference in peak voxels, between after and before duloxetine treatment, was . See [42] for details.) Coronal sections of oxaliplatin-treated macaques averaged from four macaques. Sections arranged from rostral (upper left) to caudal (lower right) and spaced 4 mm apart. R, right; L, left. Data previously published in [42].