Rescue experiment reveals that PAP is exclusively required at the spinal level to mediate the antinociceptive effects of systemic BT.

<p>hPAP (P; 250 mU) was injected i.t. into <i>A₁R^−/−,Pap^−/−</i> (n = 10) and <i>A₁R^−/−</i> (n = 10) male mice. Vehicle (V; 0.9% saline) was injected into a separate group of <i>A₁R^−/−, Pap^−/−</i> (n = 10) male mice. BT (300 mg/kg, p.o.) was administered 24 h later. One week later, BT (300 mg/kg, p.o.) was again administered to the mice that were previously injected with hPAP. Noxious thermal sensitivity in the hindpaw was measured at the indicated times. Paired t tests were used to compare responses at each time point to the response before administration of BT. *<i>P</i><0.05, **<i>P</i><0.005, ***<i>P</i><0.0005. Data are plotted as means ± s.e.m.