Knockdown of PSD-95/SAP90 delays the development of neuropathic pain in rats.
Our previous work has shown that PSD-95/SAP90 is required for NMDA receptor-mediated thermal hyperalgesia. To address the role of PSD-95/SAP90 in chronic pain, the present study investigated the effect of the deficiency of PSD-95/SAP90 on nerve injury-induced neuropathic pain. Following unilateral L5 spinal nerve injury, mechanical and thermal hyperalgesia developed within 3 days and persisted for 9 days or longer on the injured side. The intrathecal administration of antisense oligodeoxynucleotide specifically against PSD-95/SAP90, but not sense or missense oligodeoxynucleotide, dose-dependently delayed the onset of tactile allodynia and thermal hyperalgesia. These results suggest that PSD-95/SAP90 might be involved in the central mechanisms of the development of chronic neuropathic pain.
Tao
F
F
Department of Anesthesiology and Critical Care Medicine, Blalock 1415, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287-4965, USA.
Tao
Y X
YX
Gonzalez
J A
JA
Fang
M
M
Mao
P
P
Johns
R A
RA
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D004305:Dose-Response Relationship, Drug; D005528:Foot / Q000294:innervation / Q000503:physiopathology; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency*; D009437:Neuralgia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000378:metabolism* / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013126:Spinal Nerve Roots / Q000293:injuries / Q000503:physiopathology / Q000601:surgery
D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020319:Oligodeoxyribonucleotides, Antisense; C033652:postsynaptic density proteins