Potential mechanisms of neuropathic pain in diabetes

Int Rev Neurobiol. 2002;50:205-28. doi: 10.1016/s0074-7742(02)50078-7.


Abnormal sensations and pain are features of approximately 10% of all cases of diabvetic neuropathy and can cause marked diminution in the quality of life for these patients. The quality and distribution of pain are variable, although descriptions of burning pain in the hands and feet are commonly reported. Like other neuropathic pain states, painful diabetic neuropathy has an unknown pathogenesis and, in many cases, is not alleviated by nonsteriodal anti-inflammatory drugs or opiates. In the last decase, a number of behavioral and physiologic studies have revealed indices of sensory dysfunction in animal models of diabetes. These include hyperalgesia to mechanical and noxious chemical stimuli and allodynia to light touch. Animal models of painful diabetic neuropathy have been used to investigate the therapeutic potential of a range of experimental agents and also to explore potential etiologic mechanisms. There is relatively little evidence to suggest that the peripheral sensory nerves of diabetic rodents exhibit spontaneous activity or increased responsiveness to peripheral stimuli. Indeed, the weight of eveidence suggests that sensory input to the spinal cord is decreased rather than increased in diabetic rodents. Aberrant spinal or supraspinal modulation of sensory processing may therefore be involved in generating allodynia and hyperalgesia in these models. Studies have supported a role for spinally mediated hyeralgesia in diabetic rats that may reflect either a response to diminished peripheral input or a consequence of hyperglycemia on local or descending modulatory systems. Elucidating the affects of diabetes on spinal sensory processing may assist development of novel therapeutic strategies for preventing and alleviating painful diabetic neuropathy.

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus / physiopathology
  • Diabetic Neuropathies / drug therapy
  • Diabetic Neuropathies / etiology*
  • Diabetic Neuropathies / physiopathology*
  • Humans
  • Hyperglycemia / metabolism
  • Peripheral Nerves / metabolism
  • Peripheral Nerves / pathology
  • Sensation Disorders / physiopathology
  • Spinal Cord / physiology