Treadmill Training Combined with Insulin Suppresses Diabetic Nerve Pain and Cytokines in Rat Sciatic Nerve

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).