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Tolerance to Non-Opioid Analgesics is Opioid Sensitive in the Nucleus Raphe Magnus

Merab G Tsagareli1, Ivliane Nozadze, Nana Tsiklauri

  • 1Department of Neurophysiology, Beritashvili Institute of Physiology Tbilisi, Georgia.

Frontiers in Neuroscience
|August 17, 2011
PubMed

Insights

Repeated use of non-steroidal anti-inflammatory drugs (NSAIDs) in the brainstem leads to tolerance and cross-tolerance to morphine. This suggests endogenous opioid involvement in pain control and NSAID effects.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Pain Management

Background:

  • Opioid analgesics can lose effectiveness with repeated use, a phenomenon known as tolerance.
  • Non-steroidal anti-inflammatory drugs (NSAIDs) administered systemically or into the brainstem can induce pain relief and some tolerance.
  • Previous research showed NSAID microinjection into the amygdala causes tolerance and cross-tolerance to morphine.

Purpose of the Study:

  • To investigate the development of tolerance to NSAIDs administered into the nucleus raphe magnus (NRM).
  • To explore the role of endogenous opioids in NSAID-induced antinociception and tolerance within the descending pain-control system.

Main Methods:

  • Male rats received repeated daily microinjections of NSAIDs (analgin, ketorolac, xefocam) or saline into the NRM for four days.
  • Antinociceptive effects were assessed using tail-flick (TF) and hot plate (HP) tests.
  • The effect of naloxone, a μ-opioid antagonist, on NSAID antinociception and tolerance development was evaluated.

Main Results:

  • Repeated NSAID administration into the NRM resulted in progressively reduced antinociception compared to saline controls, indicating tolerance.
  • Naloxone administration into the NRM significantly reduced NSAID antinociceptive effects on the first day.
  • Naloxone impeded the development of tolerance to NSAIDs on the second day of testing.

Conclusions:

  • These findings support the involvement of endogenous opioids in NSAID-induced antinociception and tolerance within the NRM.
  • Repeated NSAID administration can lead to tolerance, cross-tolerance to morphine, and potential withdrawal symptoms.
  • The results have implications for understanding pain management and analgesic tolerance in human medicine.
Keywords:
antinociceptionhot plate testnon-opioid tolerancenon-steroidal anti-inflammatory drugstail-flick reflex

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