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Analgesic effect of intrathecally administered matrix metalloproteinase 2 (MMP-2) in the rat formalin test
Tatsuo Yamamoto1, Osamu Saito, Koyo Shono
1Department of Anesthesiology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan. yamatat@med.m.chiba-u.ac.jp
Abstract:
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.
Insights
Matrix metalloproteinases-2 (MMP-2) applied to the spinal cord reduced inflammatory pain in rats. This analgesic effect was specific to the early phase of the formalin test and was blocked by an MMP inhibitor.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Matrix metalloproteinases (MMPs) are enzymes degrading extracellular matrix.
- Their role in pain modulation is an area of active research.
Purpose of the Study:
- To investigate the effect of intrathecal MMP-2 on nociceptive transmission in a rat formalin test model.
- To determine if MMP inhibition affects MMP-2's action on pain.
Main Methods:
- Intrathecal injection of MMP-2 in rats undergoing the formalin test.
- Administration of an MMP inhibitor (ONO-4817) to assess antagonism.
- Observation and quantification of flinching behavior during the biphasic formalin test.
Main Results:
- Intrathecal MMP-2 (1 microg) significantly reduced phase 1 (acute) flinching behavior.
- MMP-2 did not affect phase 2 (inflammatory) flinching behavior.
- The MMP inhibitor ONO-4817 antagonized the analgesic effect of MMP-2 on phase 1, while ONO-4817 alone had no effect.
Conclusions:
- Exogenously applied MMP-2 to the spinal cord exhibits analgesic properties in the early phase of inflammatory pain.
- These findings suggest a specific role for MMP-2 in acute pain signaling within the spinal cord.
- Targeting MMPs could be a potential strategy for managing certain types of pain.
