Figure 2.

Effect of coadministration of morphine and clonidine on cold allodynia. (a) Saline-treated SPARC-null animals exhibit more acetone-evoked behaviours compared to WT mice in the acetone assay, indicative of cold hypersensitivity on the hindpaw. (b), (b′). In both SPARC-null (b) and WT (b′) mice, morphine (●) and clonidine (■) dose-dependently inhibited cold allodynia when administered systemically either alone or coadministered (i.p.) at a constant dose ratio of 100 : 1 (morphine : clonidine). (c), (c′) Isobolographic analysis applied to the data from (b), (b′). The y-axis represents the ED₅₀ for morphine, and the x-axis represents the ED₅₀ for clonidine. The lines directed from each ED₅₀ value toward zero represent the respective lower 95% confidence limits of each ED₅₀. The line connecting these two points is the theoretical additive line. The open circle on the theoretical additive line represents the calculated theoretical ED₅₀ value of the combination if the interaction is additive. The observed combination ED₅₀ (●) was not significantly different (t-test) from the theoretical additive ED₅₀ (∘) in either strain, indicating that the interaction is additive in both cases. Error bars represent ±SEM for each dose point (n = 5–11 animals/dose). See Table 1 for ED₅₀ values. ***P < 0.0001.