Fig. 4

Paw incision (PI) then drug. Immediately after closing the incision, a bolus injection of drug was given and pumps were connected for 3 days. a Mechanical allodynia was greatly reduced by both morphine and ZH853 on the first day of drug but by day 2 and 3 only ZH853 gave analgesia versus vehicle treatment. b ZH853 prevented thermal hyperalgesia for longer than morphine, but ultimately animals tolerated to both drugs by D3. However, ZH853-treated animals recovered more quickly than vehicle or morphine groups. Upon treatment with naltrexone, relapse to thermal hyperalgesia was apparent in vehicle- and morphine-treated animals but not ZH853-treated animals. c CatWalk data was highly variable and there were no differences between drug treatment groups. n indicated in bar graphs. Dashed lines indicate difference versus morphine while solid lines indicate difference versus vehicle. Error bars indicate SEM. + = veh vs morphine, # = veh vs ZH853, * = morphine vs 853. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001