Figure 4.

GABA_AR-Mediated Antinociception and Anesthesia is Impaired in Pd1^−/− Mice

(A and B) GABA_AR-mediated antinociception in WT and Pd1^−/− mice. (A) von Frey testing showing the effect of intrathecal THIP (3 nmol) on CFA-induced inflammatory pain. p = 0.0001, WT versus Pd1^−/−, two-way ANOVA, followed by Bonferroni's post hoc test. (B) von Frey testing showing the effect of intrathecal THIP (3 nmol) on CFA-induced inflammatory pain in mice pretreated with IgG4 or nivolumab (1 μg, i.t.). p = 0.0006, IgG4 + THIP versus nivolumab + THIP, two-way ANOVA, followed by Bonferroni's post-hoc test.

(C–F) GABA_AR-mediated anesthesia in WT and Pd1^−/− mice. (C) Experimental setup used to assess isoflurane anesthesia-mediated loss of righting reflex (LORR). (D) Dose-response curves of the fraction of LORR in WT or Pd1^−/− mice at various concentrations of isoflurane. The curves were drawn according to the Hill equation. (E) The effects of different doses of isoflurane on induction and emergence time in WT or Pd1^−/− mice (n = 10 animals in each group). Unpaired two-tailed t test. (F) The effects of sodium pentobarbital on anesthesia induction time in WT or Pd1^−/− mice (n = 22 and 16 animals). Unpaired two-tailed t test.

All error bars indicate the mean ± SEM.