Introduction: Neuroma formation after peripheral nerve transection leads to severe neuropathic pain in amputees. Previous studies suggested physical exercise could bring beneficial effect on alleviating neuropathic pain. Yet the effect of exercise on neuroma pain still remained unclear. In addition, long-term exercise can affect the expression of neurotrophins (NTs), such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which play key roles in nociceptor sensitization and nerve sprouting following nerve injury. Here, we investigated whether long-term swimming exercise could relieve neuroma pain by modulating NTs expression.
Methods: We used a tibial neuroma transposition (TNT) rat model to mimic neuroma pain. Following TNT surgery, rats were performed swimming exercise for 5 weeks. Neuroma pain and tactile sensitivities were detected using von Frey filaments. Immunofluorescence was applied to analyze neuroma formation. NGF and BDNF expression in peripheral neuroma, dorsal root ganglion (DRG) and spinal cord were measured using ELISA and western blotting.
Results: TNT led to neuroma formation, induced neuroma pain and mechanical allodynia in hind paw. 5-week swimming exercise inhibited neuroma formation, relieved mechanical allodynia in the hind paw and neuroma pain in the lateral ankle. The analgesic effect lasted for at least one week, even the exercise ceased. TNT elevated the expressions of BDNF and NGF in peripheral neuroma, DRG and spinal cord to different extents. Swimming also decreased the elevation of NTs expression.
Conclusions: Swimming exercise not only inhibits neuroma formation induced by nerve transection, but also relieves pain behavior. These effects might be associated with the modulation of NTs.
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