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Morphine tolerance and transcription factor expression in mouse spinal cord tissue

X Li1, J D Clark

  • 1Veterans Administration Palo Alto Health Care System, CA, USA.

Neuroscience Letters
|October 3, 1999
PubMed

Insights

Opioid tolerance involves changes in gene expression within the spinal cord. Key transcription factors like cyclic AMP response element binding protein (CREB) and Fos B increase, particularly in sensory processing areas.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Opioid analgesics are widely used, but tolerance limits their long-term efficacy.
  • Mechanisms underlying opioid tolerance, particularly changes in gene expression, remain poorly understood.

Purpose of the Study:

  • To investigate alterations in transcription factor gene expression in the spinal cord associated with morphine tolerance.
  • To identify specific molecular changes contributing to the development and maintenance of opioid tolerance.

Main Methods:

  • Utilized C57BL/6 mice rendered tolerant to morphine.
  • Employed Western blot analysis to quantify protein levels of transcription factors.
  • Conducted immunohistological staining to localize changes within the spinal cord.

Main Results:

  • Significant increases in cyclic AMP response element binding protein (CREB) and phospho-CREB immunoreactivity (1.9-fold and 2.4-fold, respectively).
  • Elevated levels of Fos B and deltaFos B immunoreactivity (2.2-fold and 2.3-fold, respectively).
  • No significant change observed in c-Fos expression; increased phospho-CREB and Fos B/deltaFos B localized to the dorsal horn.

Conclusions:

  • Chronic opioid exposure induces significant changes in gene expression within the spinal cord.
  • Upregulation of CREB and Fos B family proteins in spinal cord sensory processing areas is linked to opioid tolerance.
  • These molecular alterations provide insight into the neurobiological basis of opioid tolerance.

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