Knockdown of PSD-95/SAP90 delays the development of neuropathic pain in rats

Neuroreport. 2001 Oct 29;12(15):3251-5. doi: 10.1097/00001756-200110290-00022.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Disease Models, Animal
  • Disks Large Homolog 4 Protein
  • Dose-Response Relationship, Drug
  • Foot / innervation
  • Foot / physiopathology
  • Hyperalgesia / drug therapy
  • Hyperalgesia / metabolism
  • Hyperalgesia / physiopathology
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Membrane Proteins
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / deficiency*
  • Neuralgia / drug therapy
  • Neuralgia / metabolism*
  • Neuralgia / physiopathology
  • Oligodeoxyribonucleotides, Antisense / pharmacology*
  • Pain Measurement / drug effects
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Peripheral Nerve Injuries
  • Peripheral Nerves / metabolism*
  • Peripheral Nerves / physiopathology
  • Peripheral Nervous System Diseases / drug therapy
  • Peripheral Nervous System Diseases / metabolism*
  • Peripheral Nervous System Diseases / physiopathology
  • Physical Stimulation
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Nerve Roots / injuries
  • Spinal Nerve Roots / physiopathology
  • Spinal Nerve Roots / surgery

Substances

  • Disks Large Homolog 4 Protein
  • Dlg4 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Oligodeoxyribonucleotides, Antisense
  • postsynaptic density proteins