PAP has long-lasting, localized antinociceptive effects in chronic inflammatory and neuropathic pain models. (A, B) CFA was injected into one hindpaw. One day later hPAP (250 mU) was injected into the ipsilateral popliteal fossa. Inflamed and non-inflamed (contralateral) hindpaws were tested for (A) thermal and (B) mechanical sensitivity. (C, D) The sural and common peroneal branches of the sciatic nerve were ligated and then transected (injure-arrow). Two days later, hPAP (250 mU) was injected into the ipsilateral popliteal fossa. Injured and non-nerve injured (contralateral) hindpaws were tested for (C) thermal and (D) mechanical sensitivity. (E, F) Preemptive study. hPAP (250 mU) was injected into the popliteal fossa. One day later, SNI surgery was performed on the ipsilateral leg. Injured and non-nerve injured (contralateral) hindpaws were tested for (E) thermal and (F) mechanical sensitivity. (A-F) Ipsi = ipsilateral hindpaw. Contra = contralateral hindpaw. Contralateral popliteal fossa was not injected. Wild-type (n = 9-10) and A
R−/− (n = 10) male mice in each cohort. Data are plotted as means ± s.e.m. T-tests were used to compare responses at each time point between genotypes, same paw comparisons. +
P < 0.05, ++
P < 0.005, +++
P < 0.0005.