Spinal cord neuroplasticity following repeated opioid exposure and its relation to pathological pain

Ann N Y Acad Sci. 2001 Mar:933:175-84. doi: 10.1111/j.1749-6632.2001.tb05823.x.

Abstract

Convincing evidence has accumulated that indicates neuroplastic changes within the spinal cord in response to repeated exposure to opioids. Such neuroplastic changes occur at both cellular and intracellular levels. It has been generally acknowledged that the activation of N-methyl-D-aspartate (NMDA) receptors plays a pivotal role in the development of neuroplastic changes following repeated opioid exposure. Intracellular cascades can also be activated subsequent to NMDA receptor activation. In particular, protein kinase C has been shown to be a key intracellular element that contributes to the behavioral manifestation of neuroplastic changes. Moreover, interactions between NMDA and opioid receptors can lead to potentially irreversible degenerative neuronal changes in the spinal cord in association with the development of opioid tolerance. Interestingly, similar cellular and intracellular changes occur in the spinal cord following peripheral nerve injury. These findings indicate that interactions exist in the spinal cord neural structures between two seemingly unrelated conditions-chronic opioid exposure and a pathological pain state. These observations may help understand mechanisms of chemical intolerance and multiple chemical sensitivity as well as have significant clinical implications in pain management with opioid analgesics.

Publication types

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

MeSH terms

  • Analgesics / pharmacology*
  • Analgesics, Opioid / pharmacology
  • Analgesics, Opioid / therapeutic use
  • Analgesics, Opioid / toxicity
  • Animals
  • Benzamides / therapeutic use
  • Dizocilpine Maleate / therapeutic use
  • Drug Tolerance
  • Hot Temperature / adverse effects
  • Humans
  • Hyperalgesia / drug therapy
  • Hyperalgesia / etiology*
  • Hyperalgesia / physiopathology
  • Morphine / pharmacology
  • Morphine / therapeutic use
  • Morphine / toxicity
  • Multiple Chemical Sensitivity / physiopathology
  • N-Methylaspartate / toxicity
  • Narcotics / pharmacology
  • Narcotics / toxicity*
  • Nerve Degeneration / chemically induced*
  • Nerve Tissue Proteins / drug effects
  • Nerve Tissue Proteins / physiology
  • Neuralgia / physiopathology*
  • Neuronal Plasticity / drug effects*
  • Nitric Oxide / physiology
  • Phosphorylation
  • Poly(ADP-ribose) Polymerases / physiology
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / physiology
  • Protein Kinase C / physiology
  • Protein Processing, Post-Translational
  • Rats
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Receptors, Opioid / drug effects*
  • Receptors, Opioid / physiology
  • Receptors, Opioid, mu / drug effects
  • Receptors, Opioid, mu / physiology
  • Sciatic Nerve / injuries
  • Spinal Cord / drug effects*
  • Spinal Cord / physiopathology

Substances

  • Analgesics
  • Analgesics, Opioid
  • Benzamides
  • Narcotics
  • Nerve Tissue Proteins
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Opioid
  • Receptors, Opioid, mu
  • Nitric Oxide
  • N-Methylaspartate
  • Dizocilpine Maleate
  • benzamide
  • Morphine
  • Poly(ADP-ribose) Polymerases
  • Protein Kinase C