Morphine and Clonidine Synergize to Ameliorate Low Back Pain in Mice
Figure 1
Morphine and clonidine synergize to attenuate axial pain in SPARC-null mice. (a) Saline-treated SPARC-null animals spend less time in immobility compared to WT mice in the tail suspension assay, indicative of axial pain. (b), (b′) In SPARC-null mice (b), morphine and clonidine (■) dose-dependently inhibited axial pain when administered systemically either alone or coadministered (i.p.) at a constant dose ratio of 100 : 1 (morphine : clonidine). In WT mice (b′), morphine (●) and clonidine (■) dose-dependently inhibited axial pain when administered systemically, but the combination lacked efficacy. (c) Isobolographic analysis applied to the data from (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 are the 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 significantly (; -test) lower than the theoretical additive ED50 (), indicating that the interaction is synergistic. An isobolograph was not plotted for WT mice, since the combination lacked efficacy in this assay. Error bars represent ±SEM for each dose point ( = 5–11 animals/dose). See Table 1 for ED50 values. .
