Matrix metalloproteinases (MMPs) are a family of extracellular endopeptidases that selectively degrade components of the extracellular matrix. In the present study, the authors examined the effect of intrathecal injection of MMP-2 on the nociceptive transmission during the rat formalin test (a model of inflammatory pain). The paw formalin injection induces biphasic flinching (phase 1: 0-6 min; phase 2: 10-60 min) of the injected paw. Intrathecal injection of 1 microg of MMP-2 depressed the phase 1 agitation behavior, but not the phase 2 agitation behavior, and this effect of MMP-2 was antagonized by ONO-4817, an MMP inhibitor. ONO-4817 itself had no effect on the formalin test. These data suggest that exogenously applied MMP-2 to the spinal cord produces analgesic effects in the rat formalin test.