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Protease-activated receptors and inflammatory hyperalgesia Vergnolle NMem Inst Oswaldo Cruz 2005[Mar]; 100 Suppl 1 (ä): 173-6Recent advances in basic science pointed to a role for proteinases, through the activation of proteinase-activated receptors (PARs) in nociceptive mechanisms. Activation of PAR1, PAR2 and PAR4 either by proteinases or by selective agonists causes inflammation inducing most of the cardinal signs of inflammation: swelling, redness, and pain. Sub-inflammatory doses of PAR2 agonist still induced hyperalgesia and allodynia while PAR2 has been shown to be implicated in the generation of hyperalgesia in different inflammatory models. In contrast, sub-inflammatory doses of PAR1 increases nociceptive threshold, inhibiting inflammatory hyperalgesia, thereby acting as an analgesic agent. PARs are present and functional on sensory neurons, where they participate either directly or indirectly to the transmission and/or inhibition of nociceptive messages. Taken together, the results discussed in this review highlight proteinases as signaling molecules to sensory nerves. We need to consider proteinases and the receptors that are activated by proteinases as important potential targets for the development of analgesic drugs in the treatment of inflammatory pain.|Animals[MESH]|Humans[MESH]|Hyperalgesia/*enzymology/physiopathology[MESH]|Inflammation/*enzymology/physiopathology[MESH]|Neurons, Afferent/*enzymology[MESH]|Receptors, Proteinase-Activated/metabolism/*physiology[MESH] |
