title: Treadmill training combined with insulin suppresses diabetic nerve pain and cytokines in rat sciatic nerve.
abstract: BACKGROUND
  Insulin therapy plays a critical role in managing type 1 diabetes mellitus, and exercise produces alterations in pain sensation. This experiment explored the effects of insulin therapy combined with treadmill training on diabetic neuropathic pain and on the expression of malondialdehyde (MDA) and cytokines.
  
  
  METHODS
  Rats were given 4 weeks of insulin (100 IU/kg) therapy and treadmill training (30-60 min/d of training at 20-25 m/min) each day beginning on day 3 after streptozotocin (65 mg/kg, IV) injection and continuing until day 27. Sensitivity to heat and mechanical stimuli and the expression of interleukin (IL)-10, IL-6, tumor necrosis factor-α, and MDA in the sciatic nerve were estimated.
  
  
  RESULTS
  We showed that 2 to 4 weeks of treadmill training, insulin treatment, or their combination increased both paw withdrawal thresholds and latencies compared with the same regimen in sedentary diabetic rats (all P < 0.0022). Treatment with insulin, but without treadmill training, had significant effects on glycemic control (P < 0.0001) and restored body weight (P < 0.0001) in the diabetic rats. The diabetic rats demonstrated the upregulation (all P < 0.009) of IL-6, MDA, and tumor necrosis factor-α in the sciatic nerve on days 14 and 28 after streptozotocin treatment, whereas in diabetic rats receiving insulin, treadmill training, or a combination (all P < 0.01), this upregulation was decreased. Insulin, treadmill training, or the combination increased IL-10 expression (all P < 0.0051) in all diabetic rats.
  
  
  CONCLUSIONS
  Treadmill training combined with insulin therapy showed the best improvements in tactile allodynia and thermal hyperalgesia among our 3 treatment groups. The benefits of insulin intervention and treadmill training could be related to chronic inflammation (proinflammatory cytokines) and oxidative stress (MDA).
authors.affiliation: From the Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan; Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan; Department of General Surgery, Chi-Mei Medical Center, Tainan and Liouying, Taiwan; Department of Electrical Engineering, Southern Taiwan University of Science and Technology, Tainan, Taiwan; and Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Chen
authors.forename: Chong-Chi
authors.initials: CC
authors.lastname: Chiu
authors.forename: Pei-Ling
authors.initials: PL
authors.lastname: Hsieh
authors.forename: Ching-Hsia
authors.initials: CH
authors.lastname: Hung
authors.forename: Jhi-Joung
authors.initials: JJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D003131:Combined Modality Therapy; D016207:Cytokines / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D003929:Diabetic Neuropathies / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D005081:Exercise Therapy / Q000379:methods*; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D017288:Pain Threshold / Q000187:drug effects; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012420:Running; D012584:Sciatic Nerve / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D012585:Sciatica / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D016207:Cytokines; D007004:Hypoglycemic Agents; D018836:Inflammation Mediators; D007328:Insulin; D008315:Malondialdehyde