knee osteoarthritis is known to cause not only restrictions in joint functions , but also 
 major problems , such as the wear of articular cartilage and pain due to inflammatory damage 
 to the surrounding tissues1 , 2 . if the pain due to osteoarthritis persists chronically , 
 cytokines will increase in the spinal cord due to inflammatory stimulation coming from 
 peripheral regions , and the increase in cytokines will induce inflammatory responses to 
 cause damage to spinal cord nerve cells . if pain signals continuously extend from the 
 peripheral joint regions to the spinal cord , spinal cord nerve cell damage will increase to 
 develop chronic pain along with neuropathic pain , such as hyperalgesia3 . in this case , to regenerate the synapses of damaged spinal 
 cord nerve cells , growth - associated protein-43 ( gap-43 ) , which is a substance related to 
 nerve regeneration , increases in the posterior horn of the spinal cord4 . among the many methods of treating osteoarthritis patients , exercise not only reinforces 
 the regenerative capacity of articular cartilage and improves the collagen synthesis 
 network , but it also strengthens the muscles and ligaments around the knee joints5 . in addition , exercise is known to not only 
 suppress the production of pre - inflammatory cytokines , such as il-6 , il-8 , and tnf- , and 
 increase the secretion of il-10 , which has anti - inflammatory effects to reduce inflammatory 
 responses in the joints and the spinal cord , but it also increases the expression of 
 neurotrophic factors , increased neurotrophic factor expression could promote the gap-43 
 expression , thereby enhancing the nerve regeneration capacity3 , 6 , 7 . as such , the purpose of exercise treatment for osteoarthritis 
 patients is to not only enhance joint functions , but also relieve pain , thereby enhancing 
 quality of life . therefore , the present study was conducted to examine the effects of 
 exercise on the recovery of spinal cord nerve cells damaged due to pain signals , which are a 
 major symptom of osteoarthritis . experimental procedures were performed in accordance with the protocols established by the 
 institution of animal care and use committee ( iacuc ) at the daegu university , based on the 
 nih guidelines for the care and use of laboratory animals ( nih , 1996 ) . adult male 
 sprague - dawley rats ( 810 weeks of age , weight 250300  g , n=40 ) were used and housed at a 
 controlled temperature at 25  2 c with 12  h light / dark cycle and free access to 
 food and water . induction of osteoarthritis by monosodium iodoacetate ( mia , sigma , st louis , mo , america ) 
 was performed briefly , 3  mg mia in 50ul saline was injected through the patella tendon into 
 the right knee joint8 . injected rats were randomly divided into 4 
 groups : sham control group without mia injection ( sg ) , control group with injected mia ( cg ) , 
 oa without exercise ( neg ) , oa with exercise ( eg ) . three weeks after oa induction , exercise group was habituated on motor - driven treadmill at 
 a speed of 10 m / min for 2 days to reduce their stress . the exercise group was submitted to 
 4-week training program on a treadmill for 5 days / week , 30  min / day , 16 m / min velocity which 
 corresponded to approximately 6070% vo2 max . spinal cord were removed , postfixed for 30  min , then rinsed and stored in 0.2  m phosphate 
 buffer ( pb ) overnight . spinal cord were sectioned with a microtome in serial section of 30 
 um , collected on slides and sections were performed immunohistochemistry . briefly , sections 
 were rinsed 5  min and incubated for 1hr rt in tbs ( tris - buffered saline ) containing 5% 
 donkey serum ( sigma aldrich , wien , austria ) , 1% bsa ( bovine serum albumin , sigma - aldrich ) . the sections were incubated for immunohistochemistry with the primary antibody ( rabbit 
 polyclonal gap-43 , 1:500 , chemion international , usa ) overnight at 4c . subsequently , the sections were rinsed 5  min , after which the abc complex ( vector 
 laboratories ) was applied to each section for 1hr at room temperature , antibody binding was 
 visualized using a commercially available dab substrate solution ( vector laboratories ) . for 
 quantitative analysis of positive immunoreactivity was measured using computer - assisted 
 image analysis and is reported here as the proportional area of tissue occupied by 
 immunohistochemically stained . data was calculated by pixel and were analyzed using spss for 
 windows version 18.0 . and expressed as mean  standard deviation ( sd ) . in this study , a results of measuring the expression of gap-43 , gap-43 was observed in all 
 groups , showed that the significant difference in each group ( table 1table 1.the comparison of expression of ngf in spinal cord between four groups unit ; 
 pixelexpressions of gap-43 ( mean  sd)group ( n=40)sg ( n=10)cg ( n=10)neg ( n=10)eg ( n=10)8,306.6  541.711,558.2  881.618,213.5  603.322,986.4  1239.6sg : sham group ; cg : control group ; neg : no exercise group ; eg : exercise group ; mean  
 sd : mean  standard deviation . significant difference from sg . , significantly higher gap-43 expression were 
 found in neg and eg groups . in particular , it was confirmed that the highest expression of 
 gap-43 in the group which performed treadmill exercise . sg : sham group ; cg : control group ; neg : no exercise group ; eg : exercise group ; mean  
 sd : mean  standard deviation . if the 
 pain signals generated by the knee joint are continuously delivered to the spinal cord , 
 cytokines , which are an inflammation - inducing substance , will increase in the spinal cord to 
 cause inflammatory responses in the spinal cord so that nerve cells are damaged and the 
 sensory neurons in the spinal dorsal horn become sensitive , resulting in the occurrence of 
 neuropathic pain , such as hyperalgesia4 , 9 . when the central nervous system s nerve cells have been damaged , activities for the 
 protection and regeneration of the damaged region increase . astrocytes , which are neuroglia 
 cells , proliferate , neurotrophic factors , such as ngf , brain - derived neurotrophic factor 
 ( bdnf ) , and neurotrophic-3 ( nt-3 ) , increase , and these neurotrophic factors lead to 
 increases in the expression of gap-43 , which acts directly in the secretion of 
 neurotransmitters and axonal regeneration10 , 11 . in the present study , to examine whether exercise affects the expression of gap-43 , which 
 plays important roles in nerve cell regeneration and recovery in osteoarthritic white rats 
 spinal cords , rats were induced to perform treadmill exercises , and the state of the 
 expression of gap-43 in the posterior horn of the spinal cord was examined through 
 immunohistochemical staining . upon examining the state of the expression of gap-43 , it could 
 be seen that gap-43 increased in the cg compared to the sg , and this can be judged as 
 indicating spinal cord nerve cell damage due to osteoarthritis , as presented in a study 
 conducted by orita et al . in addition , orita et al . observed the gap-43 expression in the spinal cord , which did not 
 clearly increase at the early stage of the onset of osteoarthritis , but it remarkably 
 increased from 14 days after the onset , and the lesion progressed to 28 days after the onset 
 when the experiment terminated . this is consistent with the results of the present study , 
 indicating that the gap-43 expression significantly increased in the neg compared to in the 
 cg . therefore , gap-43 seems to have increased over time through natural healing to heal the 
 damaged nerve cells . the significantly higher expression could be seen in the eg , which 
 performed exercise , compared to the neg . based on the results of an analysis of previous 
 studies , this result can be judged as indicating that the damaged nerve cells were actively 
 being recovered as gap-43 increased thanks to exercise . when the above - mentioned results were viewed comprehensively , it could be seen that 
 exercise increased the gap-43 expression in the spinal cord to promote the regeneration of 
 spinal cord nerve cells damaged due to chronic osteoarthritis . also , the increase in the 
 regeneration of nerve cells damaged due to inflammatory responses is thought to have 
 positive effects on treatment for pain relief .
[ purpose ] the purpose of the study was to investigate the effects of exercise on the 
 recovery of spinal cord nerve cells damaged due to pain signals which are a major symptom 
 of osteoarthritis . 
 [ subjects and methods ] adult male sprague - dawley rats ( n=40 ) were used 
 and induction of osteoarthritis by monosodium iodoacetate . 
 injected rats were randomly 
 divided into 4 groups : sham control group without mia injection ( sg ) , control group with 
 injected mia ( cg ) , oa without exercise ( neg ) , oa with exercise ( eg ) . 
 sham control group 
 was injected normal cell line instead of mia . 
 the exercise group was submitted to 4-week 
 training program on a treadmill for 5 days / week , 30  min / day , 16 m / min velocity , then 
 spinal cord were removed and measured the gap-43 expression by immunohistochemistry 
 analysis . [ results ] in this study , a results of measuring the expression of gap-43 . 
 gap-43 
 was observed in all groups , showed that the significant difference in each group . 
 [ conclusion ] it could be seen that exercise increased the gap-43 expression in the spinal 
 cord to promote the recovery of spinal cord nerve cells damaged due to chronic 
 osteoarthritis .