Loperamide and morphine dose response effect on paw withdrawal latency to heat is significantly shifted after intraplantar administration of herpes simplex virus that encodes μ-opioid receptor (hsvMOR) versus herpes simplex virus that encodes preproenkephalin (hsvPPE) and hsvMOR + preproenkephalin (PPE) in nerve-injured mice. (A) The loperamide dose-response curve was significantly shifted to the left in animals infected with μ-opioid receptor (MOR) virus (day 16 postinfection). *P < 0.001 compared with control. The loperamide dose-response curve in PPE–infected mice was comparable to that of control virus–infected mice at low doses (0.17 to 1.0 mg/kg); however, at higher cumulative doses, the PPE–infected mice were nonresponsive to loperamide. MOR + PPE virus–infected mice were largely nonresponsive to loperamide. (B) The morphine dose-response curve was shifted to the left in animals infected with MOR (day 19 postinfection). *P < 0.001 compared with control. The morphine dose-response curve was shifted to the right in animals infected with MOR + PPE as compared to that in controls. In contrast, the morphine dose-response curve of PPE–infected mice was comparable that of control virus–infected mice. The percentage of maximum analgesia was calculated based on the formula: (measured PWL [s] – predrug PWL [s])/(20 – predrug PWL [s]) × 100. Bonferroni post hoc test was used for multiple comparisons. PWL = paw withdrawal latency.