CHARACTERISTICS OF NERVE GROWTH-FACTOR INDUCED HYPERALGESIA IN ADULT-RATS - DEPENDENCE ON ENHANCED BRADYKININ-1 RECEPTOR ACTIVITY BUT NOT NEUROKININ-1 RECEPTOR ACTIVATION

Treatment of adult rats with a single dose of nerve growth factor (NGF , 1 mg/kg, i.p.) results in a prolonged hypersensitivity to noxious th ermal stimulation which becomes noticeable within 30 min of administra tion and lasts for several days. A significant mechanical hyperalgesia develops within 7 h following injection of NGF and persists for up to 7 days. In the present set of experiments we describe certain quantit ative features of this hyperalgesia. The initial thermal hyperalgesia can be highly variable and is associated to some degree with the prese nce of an overt immunologic reaction. The mechanical hyperalgesia is r eproducible enough to reveal a clear dependency on the dose of NGF. We also examined the pharmacological properties of the NGF-induced hyper algesia. The bradykinin BK1 receptor antagonist des-Arg(9)[Leu(8)]BK t ransiently blocked the thermal hyperalgesia when injected 1 day after NGF administration whereas mechanical thresholds were further reduced under this protocol. The BK2 antagonist HOE 140 had no effect on this late NGF-induced hyperalgesia. Injection of the neurokinin NK1 recepto r antagonist CP-96345 or its inactive enantiomer CP-96344 one day afte r NGF both induced a transient block of NGF-induced thermal hyperalges ia indicating a non-specific effect rather than an action at NK1 recep tors. This was confirmed by finding no reversal of NGF-induced hyperal gesia by RP67580, another NK1 receptor blocker. These results suggest upregulation and activation of BK1 but not NK1 receptors as an additio nal, probably peripheral, mechanism for the late phase of NGF-induced thermal hyperalgesia.