Hyperalgesia due to nerve injury: role of neutrophils

Neuroscience. 2000;101(3):745-57. doi: 10.1016/s0306-4522(00)00396-1.


The hypothesis that the early inflammatory cell, the neutrophil, contributes to the hyperalgesia resulting from peripheral nerve injury was tested in rats in which the sciatic nerve was partially transected on one side. The extent and time-course of neutrophilic infiltration of the sciatic nerve and innervated paw skin after partial nerve damage was characterized using immunocytochemistry. The number of endoneurial neutrophils was significantly elevated in sections of operated nerve compared to sections of sham-operated nerve for the entire period studied, i.e. up to seven days post-surgery. This considerable elevation in endoneurial neutrophil numbers was only observed at the site of nerve injury. Depletion of circulating neutrophils at the time of nerve injury significantly attenuated the induction of hyperalgesia. However, depletion of circulating neutrophils at day 8 post-injury did not alleviate hyperalgesia after its normal induction. It is concluded that endoneurial accumulation of neutrophils at the site of peripheral nerve injury is important in the early genesis of the resultant hyperalgesia. The findings support the notion that a neuroimmune interaction occurs as a result of peripheral nerve injury and is important in the subsequent development of neuropathic pain.

MeSH terms

  • Animals
  • Behavior, Animal / physiology
  • Cell Movement / drug effects
  • Cell Movement / immunology
  • Hot Temperature / adverse effects
  • Hyperalgesia / immunology*
  • Hyperalgesia / pathology
  • Hyperalgesia / physiopathology
  • Male
  • Nerve Crush / adverse effects
  • Neutrophils / drug effects
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • Pain Measurement / statistics & numerical data
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Peripheral Nerve Injuries*
  • Peripheral Nerves / immunology
  • Peripheral Nerves / physiopathology
  • Peripheral Nervous System Diseases / immunology*
  • Peripheral Nervous System Diseases / pathology
  • Peripheral Nervous System Diseases / physiopathology
  • Rats
  • Rats, Wistar
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Thermoreceptors / immunology
  • Thermosensing / immunology
  • Time Factors