Cellular prion protein protects from inflammatory and neuropathic pain

• Main Authors: Zamponi Gerald W (Author), Gadotti Vinicius M (Author)
• Format: Book
• Published: SAGE Publishing, 2011-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<p>Abstract</p> <p>Cellular prion protein (PrP^C) inhibits <it>N</it>-Methyl-<it>D</it>-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^Cnull mice show a reduced threshold for various pain behaviours.</p> <p>We compared nociceptive thresholds between wild type and PrP^Cnull 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^Cnull mice exhibited an MK-801 sensitive decrease in the paw withdrawal threshold in response both mechanical and thermal stimuli. PrP^Cnull 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^Cnull 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^Cmay already be in a state of tonic central sensitization. Altogether, our data indicate that PrP^Cexerts 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.</p>

Item Description

10.1186/1744-8069-7-59
1744-8069