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In this report, we demonstrate the transcription, expression, and DNA-binding properties of the peroxisome proliferator–activated receptor (PPAR)-γ subtype of the peroxisome proliferator–activated nuclear receptor family to the spinal cord with real-time PCR, Western blot, and electrophoretic mobility shift assay. To test the hypothesis that activation of spinal PPAR-γ decreases nerve injury–induced allodynia, we intrathecally administered PPAR-γ agonists and/or antagonists in rats after transection of the tibial and common peroneal branches of the sciatic nerve. Single injection of either a natural (15-deoxy-prostaglandin J2, 15d-PGJ2) or synthetic (rosiglitazone) PPAR-γ agonist dose-dependently decreased mechanical and cold hypersensitivity. These effects were maximal at a dose of 100 μg and peaked at ∼60 minutes after injection, a rapid time course suggestive of transcription-independent mechanisms of …