Expression of PSD-95/SAP90 is critical for N-methyl-D-aspartate receptor-mediated thermal hyperalgesia in the spinal cord.
PSD-95/SAP90, a molecular scaffold protein, attaches the N-methyl-D-aspartate receptor to cellular signaling pathways through PSD-95/DLG/Z0-1 domain interactions at neuronal synapses.(5,9) This suggests that PSD-95/SAP90 might be involved in many physiological and pathophysiological actions triggered via the N-methyl-D-aspartate receptor in the central nervous system. Here, we present evidence that suppression of the expression of PSD-95/SAP90 in the spinal cord significantly attenuated facilitation of the tail-flick reflex triggered through N-methyl-D-aspartate receptor activation but not baseline tail-flick reflex latency. Moreover, PSD-95/SAP90's messenger RNA and protein were enriched in the spinal cord and selectively distributed in the superficial dorsal horn, where PSD-95/SAP90 overlapped with the N-methyl-D-aspartate receptor. In spinal cord neurons, PSD-95/SAP90 interacted with the N-methyl-D-aspartate receptor subunits 2A/2B. It is indicated that activation of the N-methyl-D-aspartate receptor in spinal hyperalgesia results in association of the N-methyl-D-aspartate receptor with PSD-95/SAP90 and that PSD-95/SAP90 is required for noxious thermal hyperalgesia triggered via the N-methyl-D-aspartate receptor at the spinal cord level. The present findings may provide novel insights into the mechanisms for persistent sensitization of the somatosensory system.
Duke Scholars
Altmetric Attention Stats
Dimensions Citation Stats
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Spinal Cord
- Somatosensory Disorders
- Receptors, N-Methyl-D-Aspartate
- Rats, Sprague-Dawley
- Rats
- RNA, Messenger
- Neurology & Neurosurgery
- Nerve Tissue Proteins
- Membrane Proteins
- Male
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Spinal Cord
- Somatosensory Disorders
- Receptors, N-Methyl-D-Aspartate
- Rats, Sprague-Dawley
- Rats
- RNA, Messenger
- Neurology & Neurosurgery
- Nerve Tissue Proteins
- Membrane Proteins
- Male