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Peripheral and central mechanisms of NGF-induced hyperalgesia

Item Type:Article
Title:Peripheral and central mechanisms of NGF-induced hyperalgesia
Creators Name:Lewin, G.R. and Rueff, A. and Mendell, L.M.
Abstract: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.
Keywords:Central Nervous System, Electrophysiology, Hyperalgesia, Inflammation, Mast Cells, Nerve Fibers, Nerve Growth Factors, Pain Measurement, Pain Threshold, Peripheral Nervous System, Physical Stimulation, N-Methyl-D-Aspartate Receptors, Serotonin Agonists, p-Methoxy-N-methylphenethylamine, Animals, Rats
Source:European Journal of Neuroscience
Publisher:Blackwell Publishing
Page Range:1903-1912
Date:1 December 1994
Official Publication:https://doi.org/10.1111/j.1460-9568.1994.tb00581.x
PubMed:View item in PubMed

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