Journal of Neuroscience, Vol 13, 2136-2148, Copyright © 1993 by Society for Neuroscience
Nerve growth factor-induced hyperalgesia in the neonatal and adult rat
GR Lewin, AM Ritter and LM Mendell
Department of Neurobiology and Behavior, SUNY, Stony Brook 11794.
Recently, we have shown that the interaction between NGF and sensory
neurons in early postnatal periods is restricted to nociceptive afferents
(Ritter et al., 1991; Lewin et al., 1992a; Ritter and Mendell, 1992). Here
we show that administration of excess NGF to neonatal or mature animals can
lead to a profound behavioral hyperalgesia. Neonatal NGF treatment
(postnatal day 0-14) resulted in a profound mechanical hyperalgesia that
persisted until the animals had reached maturity (6 weeks of age). This
hyperalgesia could be explained by an NGF-mediated sensitization of A delta
nociceptive afferents to mechanical stimuli. This peripheral sensitization
wore off with a time course similar to that of the behavior hyperalgesia.
Treatment of animals from the second postnatal week until 5 weeks of age
(juveniles) led to a very similar behavioral hyperalgesia; however, there
was no corresponding sensitization of A delta nociceptors to mechanical
stimuli. Finally, one group of adult animals (5 weeks old) was treated
daily with single injections of NGF for between 1 and 4 d. Within 24 hr
after the first NGF injection these animals developed a mechanical
hyperalgesia of the same magnitude seen after neonatal and juvenile NGF
treatments. No sensitization of A delta nociceptive afferents was observed
in these animals. In addition to the mechanical hyperalgesia, the animals
also developed a heat hyperalgesia after one injection of NGF. The heat
hyperalgesia was apparent within 15 min after the injection; however, signs
of mechanical hyperalgesia were not seen until 6 hr after the injection. In
conclusion, it appears that the NGF- induced mechanical hyperalgesia is
brought about by different mechanisms in neonatal and adult rats.
Furthermore, in adult animals the NGF-induced mechanical and heat
hyperalgesia also appear to be attributable to two different mechanisms.
The mechanical hyperalgesia may be due to central changes (see Lewin et
al., 1992b), whereas the heat hyperalgesia is likely to result at least in
part from the sensitization of peripheral receptors to heat.