Peripheral and central mechanisms of NGF-induced hyperalgesia

Eur J Neurosci. 1994 Dec 1;6(12):1903-12. doi: 10.1111/j.1460-9568.1994.tb00581.x.


Mechanisms underlying the hyperalgesia induced by a single systemic injection of nerve growth factor (NGF) in adult rats were studied in vivo. A single dose of NGF initiated a prolonged thermal hyperalgesia to a radiant heat source within minutes that lasted for days. Animals which had been pretreated with the mast cell degranulating compound 48/80 or either one of two specific 5-hydroxytryptamine receptor antagonists (ICS 205-930 and methiothepin) also developed an NGF-induced thermal hyperalgesia, but onset was delayed by more than 3 h. In the presence of ICS 205-930 or methiothepin the early component NGF-induced hyperalgesia was reversed and the animals responded with an initial hypoalgesia to the thermal stimuli. Whereas these results indicate a peripheral mechanism for the initial thermal hyperalgesia, the later phase (7 h-4 days after NGF) appeared to be centrally maintained, since it could be selectively blocked by the non-competitive NMDA receptor antagonist MK-801. In contrast to the almost immediate thermal hyperalgesia following a single injection of NGF, a significant mechanical hyperalgesia began only after a 7 h latency. This NGF-induced mechanical hyperalgesia was not blocked by any of the treatments that attenuated the thermal hyperalgesia, indicating that a separate mechanism may be involved. Additional electrophysiological experiments showed that NGF-induced hyperalgesia was not maintained by an increased amount of spontaneous activity in C-fibres. A final result showed that endogenous release of NGF in a model of acute inflammation (complete Freund's adjuvant-induced inflammation) may be involved in the development of thermal hyperalgesia, since it could be blocked by concomitant treatment with anti-NGF antisera. These data indicate that NGF-induced thermal and mechanical hyperalgesia are mediated by different mechanisms. The rapid onset component of thermal hyperalgesia is due to a peripheral mechanism involving the degranulation of mast cells, whereas the late component involves central NMDA receptors. In contrast, the NGF-induced mechanical hyperalgesia seems to be independent of mast cell degranulation or central NMDA receptor sites.

Publication types

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

MeSH terms

  • Animals
  • Central Nervous System / drug effects
  • Central Nervous System / physiopathology*
  • Electrophysiology
  • Female
  • Hyperalgesia / chemically induced
  • Hyperalgesia / physiopathology*
  • Inflammation / chemically induced
  • Inflammation / physiopathology
  • Mast Cells / physiology
  • Nerve Fibers / physiology
  • Nerve Growth Factors / pharmacology*
  • Pain Measurement / drug effects
  • Pain Threshold / drug effects
  • Peripheral Nervous System / drug effects
  • Peripheral Nervous System / physiopathology*
  • Physical Stimulation
  • Rats
  • Rats, Inbred WKY
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Serotonin Receptor Agonists / pharmacology
  • p-Methoxy-N-methylphenethylamine / pharmacology


  • Nerve Growth Factors
  • Receptors, N-Methyl-D-Aspartate
  • Serotonin Receptor Agonists
  • p-Methoxy-N-methylphenethylamine