Characteristics of nerve growth factor induced hyperalgesia in adult rats: dependence on enhanced bradykinin-1 receptor activity but not neurokinin-1 receptor activation.

Abstract:

: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 thermal stimulation which becomes noticeable within 30 min of administration 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 quantitative features of this hyperalgesia. The initial thermal hyperalgesia can be highly variable and is associated to some degree with the presence of an overt immunologic reaction. The mechanical hyperalgesia is reproducible enough to reveal a clear dependency on the dose of NGF. We also examined the pharmacological properties of the NGF-induced hyperalgesia. The bradykinin BK1 receptor antagonist des-Arg9[Leu8]BK transiently 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 receptor antagonist CP-96345 or its inactive enantiomer CP-96344 one day after NGF both induced a transient block of NGF-induced thermal hyperalgesia indicating a non-specific effect rather than an action at NK1 receptors. This was confirmed by finding no reversal of NGF-induced hyperalgesia by RP67580, another NK1 receptor blocker. These results suggest upregulation and activation of BK1 but not NK1 receptors as an additional, probably peripheral, mechanism for the late phase of NGF-induced thermal hyperalgesia.

journal_name

Pain

journal_title

Pain

authors

Rueff A,Dawson AJ,Mendell LM

doi

10.1016/0304-3959(96)03060-6

subject

Has Abstract

pub_date

1996-08-01 00:00:00

pages

359-72

issue

2-3

eissn

0304-3959

issn

1872-6623

pii

0304-3959(96)03060-6

journal_volume

66

pub_type

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