Proteinase-activated receptors (PARs), a family of four G-protein-coupled receptors (GPCRs) (PAR1, PAR2, PAR3 and PAR4), can be cleaved by proteases that are generated and released by inflammatory cells during tissue injury and inflammation. By cleaving the PARs within the extracellular amino terminus, a tethered ligand domain is exposed and the cleaved receptors are activated. It is known that proteinases and PARs contribute to the mediation of inflammation, but the effect on pain transmission is not clear. The effect of an agonist of PAR1 in the spinal cord on the electrophysiological manifestations induced by intradermal injection of capsaicin in rats was investigated in this study. A microdialysis fiber was implanted in the spinal cord dorsal horn for artificial CSF (ACSF) or PAR1-activation peptide (PAR1-AP) pre-treatment. PAR1-AP or ACSF was perfused for 30 minutes through a microdialysis fiber implanted at the lumbar segmental level. Central sensitization was initiated by injection of capsaicin into the plantar surface of the left paw. In ACSF pretreated animals, the responses to innocuous and noxious stimuli following capsaicin injection increased 15 min after injection and were mostly recovered by 60 min later. Compared to the control animals, pre-treatment with two different concentrations of PAR1-AP, into the spinal cord dorsal horn blocked the capsaicin induced responses. The results suggest that PAR1 may be used to counteract capsaicin-induced central sensitization. (Supported by NIH grants NS09743, NS11255 & DE15814).