Different peripheral mechanisms mediate enhanced nociception in metabolic/toxic and traumatic painful peripheral neuropathies in the rat

Neuroscience. 2002;111(2):389-97. doi: 10.1016/s0306-4522(02)00009-x.


Mechanisms underlying neuropathic pain states are poorly understood. We have compared mechanisms mediating enhanced nociception of four established models of neuropathic pain produced by very different types of insults to the peripheral nervous system: streptozotocin-induced hyperalgesia, a model of diabetic (metabolic) peripheral neuropathy, vincristine-induced hyperalgesia, a model of chemotherapeutic agent (toxic) peripheral neuropathy, and chronic constriction injury and partial nerve ligation, models of trauma-induced painful neuropathies. All four models resulted in prolonged mechanical hyperalgesia (>30% decrease in mechanical nociceptive threshold) and allodynia (detected by 10-209-mN-intensity von Frey hairs). In vincristine- and streptozotocin-induced hyperalgesia, the protein kinase A, protein kinase C and nitric oxide second messenger pathways in the periphery contributed to the hyperalgesia, while N-methyl-D-aspartate (NMDA) receptor-mediated events were not detected. None of these second messengers nor the NMDA receptor, which can contribute to peripheral sensitization of nociceptors, contributed to chronic constriction injury- and partial nerve ligation-induced hyperalgesia. In all four models the hyperalgesia was not antagonized by peripheral administration of a mu-opioid agonist.Our findings support the presence of a common abnormality in second messenger signaling in the periphery to the maintenance of two very different models of non-traumatic neuropathic pain, not shared by models of trauma-induced neuropathic pain.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Hyperalgesia / chemically induced
  • Hyperalgesia / etiology
  • Hyperesthesia / chemically induced
  • Hyperesthesia / etiology
  • Male
  • Nociceptors / physiology*
  • Pain / physiopathology
  • Pain Threshold
  • Peripheral Nerve Injuries*
  • Peripheral Nervous System Diseases / complications
  • Peripheral Nervous System Diseases / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Second Messenger Systems / physiology
  • Streptozocin
  • Vincristine
  • Wounds and Injuries / complications
  • Wounds and Injuries / physiopathology*


  • Vincristine
  • Streptozocin