Exercise Alleviates Neuroma Pain Through Regulating Expression Of Nerve Growth Factor And Brain Derived Neurotrophic Factor In Rats

Background: Nowadays amputation surgery is becoming more and more common along with increasing of traffic accident,diabetic neuropathy peripheral vascular diseases and limb tumor diseases.After experiencing the big surgery hit,some amputees may be subjected to post-amputation pain.It is reported that neuroma formation after peripheral nerve transection can lead to severe neuropathic pain in amputees.And physical exercise can alleviate neuropathic pain.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 a key role in nociceptor sensitization,nerve regeneration and myelination following never injury.Here,we investigated whether extended swimming exercise could relieve neuroma pain by modulating NT expression.Methods: We used a tibial neuroma transposition(TNT)rat model.TNT was surgically induced and rats performed regular swimming exercise for 5 weeks.Neuroma pain in the lateral ankle and mechanical allodynia in the plantar skin were detected using von Frey filaments.Immunofluorescence was used to assess effect of exercise on the size of neuroma,and toluidine blue staining and transmission electron microscope were applied to detect the effect of swimming exercise on regeneration and myelination of injured nerve.NGF and BDNF expression was measured using ELISA and western blotting in peripheral and central nervous system tissues.Results: TNT caused neuroma pain in the lateral ankle and induced mechanical allodynia in the plantar skin.Swimming relieved neuroma pain and mechanical allodynia,and the analgesic effect lasted for 1 week,even when exercise was stopped.Development of TNT-induced neuroma and myelination of injured nerve was inhibited by 5 weeks swimming exercise.In addition,TNT increased levels of NGF and BDNF in peripheral neuroma,dorsal root ganglion(DRG)and spinal cord tissue to different extents.Swimming decreased the up-regulation of.NGF and BDNF expression.In the early phase after swimming intervention,NGF and BDNF expression in peripheral nervous system were decreased,and in the later phase after swimming intervention and 1 week after swimming stopping,NGF and BDNF expression in central nerve system were decreased.Conclusions: We demonstrated that 5-week swimming inhibits the formation of peripheral neuroma and myelination of injured nerve,meanwhile alleviates neuroma pain and mechanical allodynia.These effects might be associated with the modulation of NGF and BDNF.We suppose that swimming exercise may regulate the peripheral NGF and BDNF to inhibit neuroma formation and myelination of injured nerve,thereby relieving neuroma pain.In addition,down-regulation of central NGF and BDNF expression by exercise may also be involved in mitigation process of neuroma pain and the mechanical allodynia.