title: Physical exercise induces excess hsp72 expression and delays the development of hyperalgesia and allodynia in painful diabetic neuropathy rats.
abstract: BACKGROUND
  The underlying mechanism of exercise on the development of diabetes-associated neuropathic pain is not well understood. We investigated in rats whether exercise regulates the functional recovery and heat shock protein 72 (Hsp72), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 expression in streptozotocin (STZ)-induced diabetes.
  
  
  METHODS
  Male Wistar rats were divided into 4 groups: normal sedentary rats, normal rats with exercise, sedentary STZ-diabetic (SS) rats, and STZ-diabetic rats with exercise. Diabetes was induced with STZ (65 mg/kg IV). The trained rats ran daily on a treadmill 30 to 60 min/d with an intensity of 20 to 25 m/min. We monitored thermal withdrawal latency and mechanical withdrawal threshold as well as Hsp72, TNF-α, and IL-6 expression in the spinal cord and peripheral nerves.
  
  
  RESULTS
  Two weeks after STZ injection, sedentary rats exhibited a marked and sustained hypersensitivity to von Frey tactile and heat stimuli. In contrast, diabetic rats undergoing exercise demonstrated delayed progress of tactile and thermal hypersensitivity. Exercise significantly suppressed diabetes-induced blood glucose levels and body weight loss, although they were not restored to control levels. Compared with normal sedentary rats, SS rats displayed significantly higher TNF-α and IL-6 levels in the spinal cord and peripheral nerves. The STZ-diabetic rats with exercise group showed greater Hsp72 expression and similar TNF-α or IL-6 level compared with the SS group in the spinal cord and peripheral nerves on day 14 after STZ treatment.
  
  
  CONCLUSIONS
  These results suggest that progressive exercise training markedly decreases diabetes-associated neuropathic pain, including thermal hyperalgesia and mechanical allodynia. In rats, this protective effect is related to the increase of Hsp72, but not TNF-α and IL-6, expression in the spinal cord and peripheral nerves of STZ-induced diabetes.
authors.affiliation: Department of Physical Therapy, China Medical University, No. 91 Hsueh-Shih Rd., Taichung 40402, Taiwan. cywhwok@mail.cmu.edu.tw
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Chen
authors.forename: Pei-Ling
authors.initials: PL
authors.lastname: Hsieh
authors.forename: Yu-Chung
authors.initials: YC
authors.lastname: Chen
authors.forename: Ching-Hsia
authors.initials: CH
authors.lastname: Hung
authors.forename: Juei-Tang
authors.initials: JT
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003929:Diabetic Neuropathies / Q000150:complications*; D050884:HSP72 Heat-Shock Proteins / Q000096:biosynthesis*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000150:complications*; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D010525:Peripheral Nerves / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015431:Weight Loss / Q000502:physiology
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D050884:HSP72 Heat-Shock Proteins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha