Morphine and Clonidine Synergize to Ameliorate Low Back Pain in Mice
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 -axis represents the ED50 for morphine, and the -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 (-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 ( = 5–11 animals/dose). See Table 1 for ED50 values. .
