Intrathecal rosiglitazone acts at peroxisome proliferator-activated receptor-gamma to rapidly inhibit neuropathic pain in rats.

Unlabelled: In this report, we demonstrate the transcription, expression, and DNA-binding properties of the peroxisome proliferator-activated receptor (PPAR)-gamma 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-gamma decreases nerve injury-induced allodynia, we intrathecally administered PPAR-gamma 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-gamma agonist dose-dependently decreased mechanical and cold hypersensitivity.

Neuropeptide Y acts at Y1 receptors in the rostral ventral medulla to inhibit neuropathic pain.

Brain microinjection studies in the rat using local anesthetics suggest that the rostral ventral medulla (RVM) contributes to the facilitation of neuropathic pain. However, these studies were restricted to a single model of neuropathic pain (the spinal nerve ligation model) and to just two stimulus modalities (non-noxious tactile stimulus and heat). Also, few neurotransmitter systems have been shown to modulate descending facilitation.