Selective i.t. cannabinoid 2 receptor agonist AM1710 reverses CCI-induced allodynia. A, B, AM1710 reverses CCI-induced allodynia in a dose-dependent manner. A total of 36 animals were used in this experiment. Prior to surgical manipulation, all groups exhibited similar bilateral (ipsilateral and contralateral) BL thresholds (ANOVA, F(5,35) =1.982 ; p=0.1124, ANOVA, F(5,35) =1.142; p=0.3616, respectively). Following CCI, clear bilateral allodynia developed by Day 3 and continued chronically through Day 10 compared to sham-operated rats. On Day 10, compared to i.t. control injected rats, AM1710 produced a dose-dependent reversal from allodynia, with maximal reversal observed at 3 hours following the highest injected dose (10 μg). However, allodynia fully returned by 5 hours after i.t. AM1710 treatment, with allodynia remaining stable through 24 hours (ipsilateral paw ANOVA, F(15,84) = 187.6; p<0.0001; and contralateral paw, ANOVA, F(15,84)=403.7; p<0.0001). While 1.0 μg produced attenuated allodynia, 0.1 μg did not alter allodynia for either the ipsilateral or contralateral hindpaws. Post hoc analysis revealed that 1μg AM1710 produced a robust reversal from allodynia at 2 hours following i.t. injection, while all AM1710 treated animals returned to allodynia by 4 hours (p<0.001).