Cellular Prion Protein Protects from Inflammatory and Neuropathic Pain. Issue 1 (16th August 2011)

• Record Type: Journal Article
• Authors: Gadotti, Vinicius M; Zamponi, Gerald W
• Is Part Of: Molecular pain. Volume 7:Issue 1(2011)
• Publication Date: 2011-08-16
• Subjects: Prion protein -- pain -- knockout mice -- NMDA receptor -- spinal cord; Pain -- Molecular aspects -- Periodicals; Pain -- Pathophysiology -- Periodicals; Pain -- Physiological aspects -- Periodicals; 616.0472
• DOI: 10.1186/1744-8069-7-59
• Languages: English
• ISSNs: 1744-8069

Abstract

Cellular prion protein (PrP C ) inhibits N -Methyl- D -Aspartate (NMDA) receptors. Since NMDA receptors play an important role in the transmission of pain signals in the dorsal horn of spinal cord, we thus wanted to determine if PrP C null mice show a reduced threshold for various pain behaviours. We compared nociceptive thresholds between wild type and PrP C null mice in models of inflammatory and neuropathic pain, in the presence and the absence of a NMDA receptor antagonist. 2-3 months old male PrP C null mice exhibited an MK-801 sensitive decrease in the paw withdrawal threshold in response both mechanical and thermal stimuli. PrP C null mice also exhibited significantly longer licking/biting time during both the first and second phases of formalin-induced inflammation of the paw, which was again prevented by treatment of the mice with MK-801, and responded more strongly to glutamate injection into the paw. Compared to wild type animals, PrP C null mice also exhibited a significantly greater nociceptive response (licking/biting) after intrathecal injection of NMDA. Sciatic nerve ligation resulted in MK-801 sensitive neuropathic pain in wild-type mice, but did not further augment the basal increase in pain behaviour observed in the null mice, suggesting that mice lacking PrP C may already be in a state of tonic central sensitization. Altogether, our data indicate that PrP C exerts a critical role in modulating nociceptive transmission at the spinal cord level, and fit with the concept of NMDA receptor hyperfunction in the absence of PrP C .