Physical exercise induces excess hsp72 expression and delays the development of hyperalgesia and allodynia in painful diabetic neuropathy rats

Anesth Analg. 2013 Feb;116(2):482-90. doi: 10.1213/ANE.0b013e318274e4a0. Epub 2013 Jan 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Cytokines / biosynthesis
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 1 / complications
  • Diabetic Neuropathies / complications*
  • HSP72 Heat-Shock Proteins / biosynthesis*
  • Hot Temperature
  • Hyperalgesia / complications*
  • Interleukin-6 / biosynthesis
  • Male
  • Peripheral Nerves / metabolism
  • Physical Conditioning, Animal / physiology*
  • Physical Stimulation
  • Rats
  • Rats, Wistar
  • Spinal Cord / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Weight Loss / physiology


  • Blood Glucose
  • Cytokines
  • HSP72 Heat-Shock Proteins
  • Interleukin-6
  • Tumor Necrosis Factor-alpha