title: Role of postsynaptic density protein-95 in the maintenance of peripheral nerve injury-induced neuropathic pain in rats.
abstract: Our previous work has demonstrated that postsynaptic density protein-95, a molecular scaffolding protein that binds and clusters N-methyl-D-aspartate receptors at neuronal synapses, plays an important role in the development of peripheral nerve injury-induced neuropathic pain. The current study further investigated the possible involvement of postsynaptic density protein-95 in the maintenance of neuropathic pain. Mechanical and thermal hyperalgesia were induced within 3 days and maintained for 15 days or longer after unilateral injury to the fifth lumbar spinal nerve. The rats injected intrathecally with postsynaptic density protein-95 antisense oligodeoxynucleotide every 24 h for 4 days from day 7 to day 10 post-surgery exhibited not only a marked decrease in spinal cord postsynaptic density protein-95 protein expression but also a significant reduction in mechanical and thermal hyperalgesia on day 11 post-surgery. The rats injected with sense oligodeoxynucleotide did not display these changes. However, in the rats without nerve injury, postsynaptic density protein-95 antisense oligodeoxynucleotide given intrathecally every 24 h for 4 days did not affect responses to mechanical and thermal stimulation. In addition, postsynaptic density protein-95 antisense oligodeoxynucleotide did not change locomotor activity of experimental animals. Our results indicate that the deficiency of postsynaptic density protein-95 protein in the spinal cord significantly attenuates nerve injury-induced mechanical and thermal hyperalgesia during both the development and maintenance of chronic neuropathic pain. These results suggest that postsynaptic density protein-95 might be involved in the central mechanisms of chronic neuropathic pain and provide a novel target for development of new pain therapies.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Blalock 1415, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287-4965, USA.
authors.forename: F
authors.initials: F
authors.lastname: Tao
authors.forename: Y-X
authors.initials: YX
authors.lastname: Tao
authors.forename: P
authors.initials: P
authors.lastname: Mao
authors.forename: R A
authors.initials: RA
authors.lastname: Johns
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018882:Heat Stress Disorders; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D008161:Lumbosacral Region; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009841:Oligonucleotides / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010146:Pain / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000378:metabolism / Q000503:physiopathology*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology
chemical_list: D009419:Nerve Tissue Proteins; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; C033652:postsynaptic density proteins