Antinociceptive Effect of Rat D-Serine Racemase Inhibitors, L-Serine-O-Sulfate, and L-Erythro-3-Hydroxyaspartate in an Arthritic Pain Model. (12th March 2012)

• Record Type: Journal Article
• Authors: Laurido, Claudio; Hernández, Alejandro; Pelissier, Teresa; Constandil, Luis
• Other Names: Montoliu Carmina Academic Editor.; Russell James Academic Editor.
• Is Part Of: TheScientificWorldjournal. Volume 2012(2012)
• Publication Date: 2012-03-12
• Subjects: Science -- Periodicals; Technology -- Periodicals; Medicine -- Periodicals; 505
• DOI: 10.1100/2012/279147
• Languages: English
• ISSNs: 2356-6140

Abstract

Abstract : N-methyl-D-aspartic acid receptor (NMDAr) activation requires the presence of D-serine, synthesized from L-serine by a pyridoxal 5′-phosphate-dependent serine racemase (SR). D-serine levels can be lowered by inhibiting the racemization of L-serine. L-serine-O-sulfate (LSOS) and L-erythro-3-hydroxyaspartate (LEHA), among others, have proven to be effective in reducing the D-serine levels in culture cells. It is tempting then to try these compounds in their effectiveness to decrease nociceptive levels in rat arthritic pain. We measured the C-reflex paradigm and wind-up potentiation in the presence of intrathecally injected LSOS (100 μ g/10 μ L) and LEHA (100 μ g/10 μ L) in normal and monoarthritic rats. Both compounds decreased the wind-up activity in normal and monoarthritic rats. Accordingly, all the antinociceptive effects were abolished when 300 μ g/10 μ L of D-serine were injected intrathecally. Since no in vivo results have been presented so far, this constitutes the first evidence that SR inhibitions lower the D-serine levels, thus decreasing the NMDAr activity and the consequent development and maintenance of chronic pain.