Fig. 1.
The HCN antagonist ZD7288 reverses neuropathic pain behavior. a, One week after SNL, rats received equivalent volumes of intraperitoneal saline (▪), 1 mg/kg ZD7288 (○), 3 mg/kg ZD7288 (⋄), or 10 mg/kg ZD7288 (■) after baseline assessment of tactile allodynia with von Frey hairs. The redacted time course of allodynia suppression is illustrated:y-axis = 50% paw withdrawal threshold (PWT) (normal = 15 gm; allodynia = lower threshold values). At 10 mg/kg, near complete suppression of allodynia is seen. *p < 0.05, one-way ANOVA with Dunnett's multiple comparisons; n = 7–8 per group. b, The dose–response curve for ZD7288 froma: y-axis: percentage of maximum possible effect (MPE) (15 gm threshold = 100% allodynia suppression; no change from pre-drug baseline = 0%). The ED50 for allodynia suppression is ∼3 mg/kg.c, Lumbar intrathecal administration of ZD7288, 50 μg (●), had no effect on SNL-related tactile allodynia at any time point, compared with saline (○), over a 2 hr observation period:y-axis: 50% paw withdrawal threshold (PWT).