NERVE GROWTH-FACTOR EVOKES HYPERALGESIA IN MICE LACKING THE LOW-AFFINITY NEUROTROPHIN RECEPTOR P75

Endogenous nerve growth factor (NGF) has been shown to be an important mediator of inflammatory pain and exogenous application of recombinan t human NGF (rhNGF) produces pain and hyperalgesia in animals and huma ns. Since NGF can act through two receptors types, the high affinity t yrosine kinase A (trkA) receptor and the low affinity p75 receptor, we used transgenic mice lacking p75 to analyse the relative importance o f these receptors. After systemic injection of rhNGF (5 mg/kg), pharma cokinetic studies revealed similar serum levels and elimination profil es of exogenously administered rhNGF in both strains of mice. Although animals lacking p75 have increased mechanical and thermal withdrawal thresholds they developed both heat and mechanical hyperalgesia after systemic injection of rhNGF whose magnitude did not differ significant ly from wildtype animals. This means that NGF-induced hyperalgesia can occur in the absence of the p75 receptor and suggests that the trkA r eceptor is sufficient to mediate the acute noxious action of NGF. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.