Figure 4.
Morphine and oxycodindole (OCI) do not require PKCε for spinal analgesic synergy. (A, C) Dose–response curves for morphine, OCI and a 1:5 (morphine : OCI) combination of the two (open squares for relative contribution of morphine, and open circles for relative combination of OCI) in PKCε-WT (A) and -KO (C) mice. Error bars for each data point represent SEM. (B, D) Isobolograms showing OCI dose and ED50 (square) on the x-axis, morphine dose and ED50 (square) on the y-axis, theoretical additive ED50 for a 1:5 combination (open white circle on line of theoretical additivity), and observed combined ED50 (filled circle). Error bars represent 95% confidence limits. (B) Morphine and OCI produce analgesic synergy at the spinal level in PKCε-WT mice. (D) The combination of morphine and OCI remains synergistic in PKCε-KO mice. For morphine, n = 12 in PKCε-WT and n = 11 in PKCε-KO. For OCI and morphine + OCI, n = 6 for PKCε-WT and PKCε-KO. Numerical details including ED50 value for each dose–response curve, and P-value for each interaction can be found in Table 1.