| pA2 online © Copyright 2004 The British Pharmacological Society |
038P
University of Newcastle Winter Meeting December 2004 |
Effects of a CB2 agonist on carrageenan-induced decrease in mechanically-evoked withdrawal thresholds of the hindpaw S.J.R. Elmes1, S.J. Medhurst2, N.M. Clayton2, A.W. Wilson2, D.A. Kendall1 and V. Chapman1. 1School of Biomedical Sciences, Queen’s Medical Centre, University of Nottingham. 2Neurology and GI CEDD, GSK, Harlow, Essex. |
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Print abstractCannabinoid 2 (CB2) receptors are predominantly expressed in immune tissues (Galiegue et al., 1995), activation of these receptors attenuates nociceptive responses in a model of inflammatory pain (Clayton et al., 2002). The aim of this study was to determine whether pre- versus post-administration of the CB2 agonist JWH-133 and the CB1 / CB2 receptor agonist HU210 attenuated decreases in mechanically-evoked withdrawal thresholds of the rat hindpaw in the carrageenan model of inflammatory pain.
Mechanically-evoked withdrawal thresholds of the hindpaw were measured with a dynamic plantar aesthesiometer prior to, and following, intraplantar injection of 100µl of 2% carrageenan in male Random Hooded rats (180-220g). Effects of pre-administration (30 minutes before carrageenan) versus post-administration (180 minutes post carrageenan) of drugs on mechanically-evoked withdrawal thresholds were determined at 210 minutes (for pre-administered drug) and 60 minutes (for post-administered drug) post drug administration.
In naïve rats, the mechanically-evoked withdrawal threshold of the hindpaw was 28.1 ± 1.7g (n=14 rats). Following injection of carrageenan, mechanically-evoked withdrawal threshold decreased to 12.6 ± 1.5g (n=14 rats) at 180 minutes post-carrageenan.
Table 1. Effects of HU210 and JWH-133 on carrageenan-induced decrease in mechanically-evoked withdrawal thresholds of the hindpaw. Data are expressed as % inhibition or % reversal of carrageenan-induced decrease in mechanical withdrawal thresholds ± S.E.M. (n=7 rats/group). Statistical analysis compared vehicle treated group with test groups using ANOVA test with Duncan’s post hoc test, *p<0.05, **p<0.01.
Pre- and post-administration of HU210 produced a significant and dose-related inhibition and reversal, respectively, of carrageenan-induced decrease in mechanical withdrawal thresholds (Table 1). In contrast, only pre-administration of JWH-133 significantly inhibited the carrageenan-induced decrease in mechanical withdrawal threshold (Table 1). These data demonstrate a differential role of the CB1 and CB2 receptor in the induction and maintenance of mechanical hyperalgesia in the carrageenan model of inflammatory pain.
Clayton, N.M. et al., (2002). Pain. 96, 253-260.
Galiegue, S. et al., (1995). Eur J Biochem. 232, 54-61.
This study was supported by The University of Nottingham and GlaxoSmithKline.