Effect of knock down of spinal cord PSD-93/chapsin-110 on persistent pain induced by complete Freund's adjuvant and peripheral nerve injury.
PSD-93/chapsin-110 is a neuronal PDZ domain-containing protein that binds to and clusters the N-methyl-D-aspartate receptor (NMDAR) at synapses in the central nervous system. It also assembles a specific set of signaling proteins around the NMDAR and mediates downstream signaling by the NMDAR. Thus, PSD-93/chapsin-110 might be involved in many physiological and pathophysiological actions triggered via the activation of the NMDAR. In the current study, we report that abundant PSD-93/chapsin-110 protein was detected in rat spinal cord, particularly in the superficial dorsal horn. The rats injected intrathecally with PSD-93/chapsin-110 antisense oligodeoxynucleotide every 24 h for 4 days displayed not only a remarkable decrease in spinal cord PSD-93/chapsin-110 expression but also a significant reduction in the paw withdrawal responses to thermal and mechanical stimuli during complete Freund's adjuvant-induced inflammatory pain and peripheral nerve injury-induced neuropathic pain. In contrast, the rats injected intrathecally with PSD-93/chapsin-110 missense oligodeoxynucleotide did not exhibit these changes. We also found that pretreatment with PSD-93/chapsin-110 antisense oligodeoxynucleotide did not change the locomotor activity or the responses to acute noxious thermal and mechanical stimuli in intact rats. The present results indicate that the deficiency of spinal cord PSD-93/chapsin-110 protein significantly attenuates thermal and mechanical hyperalgesia in complete Freund's adjuvant- or peripheral nerve injury-induced chronic pain. This suggests that spinal cord PSD-93/chapsin-110 might be involved in the central mechanism of chronic pain. Our work might provide a new target for the therapy of chronic pain.
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 355 Ross, 720 Rutland Ave., Baltimore, MD 21205, USA.
Bosheng
B
Zhang
Feng
F
Tao
Wen-Jinn
WJ
Liaw
David S
DS
Bredt
Roger A
RA
Johns
Yuan-Xiang
YX
Tao
D000208:Acute Disease; D000818:Animals; D005620:Freund's Adjuvant; D051528:Guanylate Kinases; D006930:Hyperalgesia / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins; D008124:Locomotion; D008297:Male; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009703:Nucleoside-Phosphate Kinase / Q000235:genetics*; D020319:Oligodeoxyribonucleotides, Antisense; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D059348:Peripheral Nerve Injuries; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C501451:Mpp2 protein, rat; D009419:Nerve Tissue Proteins; D020319:Oligodeoxyribonucleotides, Antisense; C033652:postsynaptic density proteins; D005620:Freund's Adjuvant; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases