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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
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The role of nitric oxide in diabetes-induced changes of morphine tolerance in rats

Khojasteh Joharchi1, Masoumeh Jorjani

  • 1Neuroscience Research Center & Department of Pharmacology, Faculty of Medicine, Shaheed Beheshti Medical University, Tehran, Iran.

European Journal of Pharmacology
|June 30, 2007
PubMed

Insights

Diabetes alters morphine effects, reducing tolerance in diabetic rats. Nitric oxide (NO) plays a key role in modulating morphine analgesia and tolerance in diabetic states.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Endocrinology

Background:

  • Diabetes and other neuroendocrine complications can alter morphine's effects on pain relief (antinociception) and the development of tolerance.
  • Morphine antinociception is significantly reduced in diabetic rats that have developed tolerance compared to non-diabetic animals, but the underlying mechanisms remain unclear.

Purpose of the Study:

  • To investigate the role of nitric oxide (NO) in modulating morphine tolerance within a diabetic state.
  • To understand how diabetes influences the relationship between NO, morphine analgesia, and tolerance.

Main Methods:

  • Alloxan-induced diabetic rats with morphine tolerance were used.
  • Nociceptive responses were assessed using the hot-plate test.
  • Urinary nitric oxide (nitrite) levels were measured spectrophotometrically using the Griess reagent, with vanadium chloride facilitating nitrate to nitrite conversion.

Main Results:

  • Experimental diabetes enhanced morphine analgesia but diminished the degree of morphine tolerance.
  • Diabetic morphine-tolerant rats exhibited higher urinary nitrite levels compared to non-diabetic controls.
  • L-arginine administration increased NO production and morphine tolerance in diabetic rats, while aminoguanidine decreased both NO production and tolerance.

Conclusions:

  • Nitric oxide (NO) appears to play a significant modulatory role in how diabetes affects morphine analgesia and the development of tolerance.
  • These findings suggest potential therapeutic targets for managing pain and opioid tolerance in diabetic patients.

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