Fig. 4.  Opioid receptor antagonists reverse the effects of exercise on sensory hypersensitivity. (A ) Naloxone reversibly inhibited exercise effects. Exercise-trained animals (EXER) that underwent spinal nerve ligation (SNL) were administered naloxone (1 mg/kg) subcutaneously. *P < 0.05 compared with values before naloxone. (B ) Subcutaneous naloxone methiodide (N. Methiodide) (0.1 mg/kg) had no effect on tactile hypersensitivity in EXER that underwent SNL. *P < 0.05 compared with EXER that underwent SNL and received vehicle. #P < 0.05 compared with EXER that underwent SNL and received N. Methiodide. (C ) Reversal of nerve injury–induced sensory hypersensitivity by exercise is mediated by endogenous opioids in the central nervous system. Intracerebroventricular (i.c.v.) injection of N. Methiodide (2 μg) reversed exercise-training–mediated reversal of sensory hypersensitivity, whereas intrathecal (i.t.) injection of N. Methiodide (10 μg) had no effect. *P < 0.05 compared with vehicle-treated EXER that underwent SNL. (D ) Continuous naltrexone infusion (70 μg/h) prevented exercise-induced reversal of tactile hypersensitivity. *P < 0.05 versus  vehicle-infused animals. Data are given as mean (95% two-tailed CI). n = 6 animals per group. BL = presurgical baseline; SED = sedentary animals.