Nerve growth factor-induced hyperalgesia in the neonatal and adult rat

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.