Fig. 3.

Repeated low-dose JZL184 administration continues to reduce nociceptive behavior in the CCI of the sciatic nerve model of neuropathic pain, but these antinociceptive effects undergo tolerance following repeated high-dose JZL184. Acute or repeated JZL184 treatment significantly attenuated mechanical allodynia (A) and cold allodynia (B). Repeated, 6-day administration of JZL184 (4 mg/kg) remained effective at reducing both cold and mechanical allodynia, whereas JZL184 (40 mg/kg) did not differ from vehicle treatment. (C and D) Twenty-four hours later, mice given repeated high-dose JZL184 displayed cross-tolerance to THC (30 mg/kg i.p.), whereas THC retained its effectiveness in mice treated repeatedly with low-dose JZL184. Control paw represents contralateral paws of vehicle-treated mice. Data presented as the mean ± S.E.M. (n = 6–7). *P < 0.05; **P < 0.01 versus vehicle.