Proteinase-activated receptor-1 agonists attenuate nociception in response to noxious stimuli

被引:83
作者
Asfaha, S
Brussee, V
Chapman, K
Zochodne, DW
Vergnolle, N
机构
[1] Univ Calgary, Fac Med, Dept Pharmacol & Therapeut, Calgary, AB T2N 4N1, Canada
[2] Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 4N1, Canada
关键词
analgesia; thrombin; proteinase-activated receptors; pain; nociception;
D O I
10.1038/sj.bjp.0704568
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Proteinase-activated receptor-1 (PAR-1) is activated by thrombin and can be selectively activated by synthetic peptides (PAR-1-activating peptide: PAR-1-AP) corresponding to the receptor's tethered ligand. PAR-1 being expressed by afferent neurons, we investigated the effects of PAR-1 agonists on nociceptive responses to mechanical and thermal noxious stimuli. Intraplantar injection of selective PAR-1-AP increased nociceptive threshold and withdrawal latency, leading to mechanical and thermal analgesia, while control peptide had no effect. Intraplantar injection of thrombin also showed analgesic properties in response to mechanical, but not to thermal stimulus. Co-injection of PAR-1-AP with carrageenan significantly reduced carrageenan-induced mechanical and thermal hyperalgesia, while thrombin reduced carrageenan-induced mechanical but not thermal hyperalgesia. The fact that thrombin is not a selective agonist for PAR-1 may explain the different effects of thrombin and PAR-1-AP, These results identified analgesic properties for selective PAR-1 agonists that can modulate nociceptive response to noxious stimuli in normal and inflammatory conditions.
引用
收藏
页码:1101 / 1106
页数:6
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