Skip to main content
. Author manuscript; available in PMC: 2010 Aug 3.
Published in final edited form as: Pain. 2009 Dec 14;148(2):302–308. doi: 10.1016/j.pain.2009.11.015

Fig. 4.

Fig. 4

Intrathecal acetazolamide (ACT) combined with midazolam (MZL) acts synergistically to inhibit neuropathic allodynia in the spinal nerve ligation (SNL) model. (A) Predrug mechanical withdrawal thresholds were measured and ACT + MZL, at a fixed dose ratio of 1850–0.97 ng (see text for explanation) was injected intrathecally and mechanical withdrawal thresholds were reassessed at the indicated time points. A significant main effect of ACT + MZL was observed (F(3, 126) = 6.29, p = 0.0005). (B) ACT + MZL dose-dependently inhibited neuropathic allodynia with a combined dose EC50 (C) of 190 ± 141 ng, curves for ACT and MZL alone are shown for comparison. (D) Isobolographic analysis revealed that ACT and MZL act synergistically to inhibit neuropathic allodynia. The A50 for ACT given alone was 2.19 ± 0.75 μg. The A50 of MZL was 1.07 ± 0.88 ng. The theoretical additive A50 for a combined dose was 1058 ± 480 ng while the observed A50 for ACT and MZL administered together was 182 ± 65 ng. The theoretical additive mixture A50 differed from the observed A50 significantly (p < 0.001) indicating that ACT and MZL act synergistically to inhibit neuropathic allodynia. (E) MZL, ACT or MZL + ACT were given intrathecally and paw withdrawal thresholds were measured at 60 min post-drug administration to test whether ACT would restore efficacy of MZL at a dose where efficacy was lost. ACT alone and ACT + MZL significantly reversed neuropathic allodynia while MZL alone did not. *p < 0.05, **p < 0.01 with one-way ANOVA and Dunnett’s post hoc test.