M. Pawlak et al., The neurokinin-1 receptor antagonist RP 67580 reduces the sensitization ofprimary afferents by substance P in the rat, EUR J P-LON, 5(1), 2001, pp. 69-79
The inflammatory mediator substance P (SP) produces a variety of biological
effects in several tissues by binding to the tachyldnin receptor neurokini
n 1 (NK1) and, to a lesser extent, by binding to the neurokinin 2 receptor
(NK2). To assess the sensitizing effect of SP on articular afferent fibres
the NK1 receptor antagonist RP 67580 was applied in normal and acutely infl
amed rat knee joints.
Altogether 38 fine afferent nerve Fibres from the rat knee with conduction
velocities of 0.71-13.5 m/s were recorded as single units, during non-noxio
us and noxious joint rotations. SP, injected i.a. as a bolus close to the k
nee joint, was able to sensitize 45.5% (10 of 22) of the units recorded fro
m normal joints and 33.3% (five of 15) of afferents from inflamed joints. T
he following i.a. application of RP 67580 in a range of 20 200 nmol antagon
ized in a dose-dependent manner the sensitizing effect of SP in a large pro
portion of slowly conducting articular afferents from normal (66.7%) and in
flamed (46.2%) knee joints. Subsequent SP application enhanced the afferent
sensitivity further. The electrophysiological results presented here furth
er support the suggestion that the sensitization of afferents by SP in the
rat knee joint is mediated mainly by the NK, receptor, which is probably lo
cated on the primary afferents. (C) 2001 European Federation of Chapters of
the International Association for the Study of Pain.