| pA2 online © Copyright 2004 The British Pharmacological Society |
160P
GKT, University of London Winter Meeting December 2003 |
|
Effects
of peripheral injection of a CB2
receptor agonist, JWH-133, on carrageenan-induced expansion of peripheral
receptive fields of spinal neurones in anaesthetised rats |
|
Print abstractCannabinoid 2 (CB2) receptors are predominantly located outside of the central nervous system. Activation of CB2 receptors inhibits acute nociception and inflammatory hyperalgesia (Malan et al.,2002). The aim of this study was to investigate the effects of peripheral injection of the CB2 receptor agonist JWH-133 on carrageenan-induced expansion of peripheral receptive fields of dorsal horn neurones in rats.
Extracellular recordings of convergent dorsal horn neurones were made in anaesthetised (1% halothane in 66% N2O / 33% O2) male Sprague Dawley rats (230-300g) (Chapman et al., 1994). Innocuous (6g) and noxious (21g) von Frey hairs (mechanical puntate stimulation) were employed to map peripheral receptive fields of dorsal horn neurones on the hindpaw of rats before and after intraplantar injection of 100µl of 2% carrageenan. Effects of intraplantar pre-administration (30mins prior) of JWH-133 (15µg in 50µl) on carrageenan-induced expansion of peripheral receptive fields were determined. Statistical analysis was performed using repeated measures ANOVA, Dunnett's post hoc test and Mann Whitney test.
Intraplantar carrageenan injection induced a significant expansion of innocuous and noxious receptive fields of neurones (Fig. 1). Peripheral pre-administration of the CB2 receptor agonist JWH-133 significantly inhibited carrageenan-induced expansion of peripheral receptive fields of dorsal horn neurones (Fig.1).
Fig. 1. Effects of intraplantar pre-administration of JWH-133 on carrageenan-induced expansion of peripheral receptive fields of dorsal horn neurones. *p<0.05,***p<0.001 compared to pre-carrageenan control data. Comparison between carrageenan and carrageenan plus JWH-133 #p<0.05, ##p<0.01.
Peripheral injection of carrageenan significantly increases innocuous and noxious receptive field areas of spinal dorsal horn neurones. Mechanisms underlying the expansion of receptive fields may include local release of inflammatory mediators, which sensitise primary afferent fibres, and recruitment of normally silent mechano-receptors. The reported peripheral CB2 receptor mediated inhibition of carrageenan-induced expansion of peripheral receptive fields may be mediated by the inhibition of release of inflammatory mediators from immune cells or direct effects on peripheral nerves.
Chapman V. et al.,
(1994). Anesthesiol. 81, 1429-1435.
Malan T.P. et al., (2002). Chem Phys lip. 121, 191-200.
Supported by University of Nottingham and GSK.