Resumo

Objective: Exercise-induced synaptic plasticity in the spinal cord, may help to recover motor and sensory function following nerve injury. We investigated whether a chronic forced swimming activity influences tactile stimulus-induced neuropathic pain hypersensitivity and the phosphorylation status of the transcription factor CREB. Methods: adult Balb/C male mice weighting 25-35 g were used. Neuropathic pain was induced by partial sciatic nerve ligation whereas sham operated mice were used as control. Chronic exercise activity was performed by swim training which lasted 40 min/day, 5 days/week for 6 weeks. Another group of nerve injuried animals swam for the same period but were left untrained for additional 4 weeks. Control animals swam for 30 s over the same periods. The development of tactile hypersensitivity following nerve lesion was monitored by von Frey filaments whereas the phosphorylation of CREB was evaluated by western blots. Results: Seven days after nerve injury, animals showed a marked hypersensitivity to mechanical stimuli which lasted for at least 7 weeks (p < 0.01, Mann-Whitney test, n= 8). However, under moderate swim exercise training, injuried mice showed a progressive recovery of the sensory abnormality from the second week of training (p < 0.01, Mann-Whitney test, n= 8). By the end of six weeks of training no difference was observed in the mechanical threshold of injuried and sham-operated animals (p > 0.05, Mann-Whitney test). No sensory abnormality was observed in non-lesioned mice submitted to chronic exercise training. In addition, peripheral nerve injury marked increases CREB phosphorylation which is reversed by six weeks of forced swimming. Interestingly, four weeks after the end of forced swimming the levels of pCREB remain low when compared to animals with nerve injury without swimming exercise (p < 0.05, Student t-test, n= 8). Conclusion: Our data indicate that the physical training is effective in treating chronic neuropathic pain in a mouse model. In addition, the behavioral recovery of the sensory abnormality correlates with CREB inhibition in the spinal cord dorsal horn suggesting an involvement of this transcription factor in the antinociceptive mechanisms induced by physical exercise.