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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
07:23

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Stimulation of peripheral nociceptor endings by low dose morphine and its signaling mechanism

Takeshi Ono1, Makoto Inoue, M Harunor Rashid

  • 1Department of Anesthesiology, Nagasaki University School of Medicine, Nagasaki, Japan

Neurochemistry International
|September 6, 2002
PubMed

Insights

Peripheral morphine at extremely low doses activates sensory nerve endings via mu-opioid receptors (MOP-R), triggering substance P (SP) release and a flexor response in mice.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Pain Research

Background:

  • Peripheral administration of opioids can modulate pain pathways.
  • The role of peripheral mu-opioid receptors (MOP-R) in mediating acute responses is not fully understood.

Purpose of the Study:

  • To investigate the effects of very low-dose peripheral morphine on nociception in mice.
  • To elucidate the underlying molecular mechanisms, including receptor involvement and downstream signaling pathways.

Main Methods:

  • Intraplantar administration of morphine and agonists/antagonists in mice.
  • Assessment of flexor responses as a measure of nociception.
  • Pharmacological inhibition of MOP-R, substance P (SP) pathways, and intracellular signaling cascades.

Main Results:

  • Very low doses (amol range) of peripheral morphine induced a dose-dependent flexor response.
  • This response was mediated by peripheral MOP-R activation and subsequent SP release from nociceptor endings.
  • Downstream signaling involved phospholipase C (PLC) activation and calcium mobilization.

Conclusions:

  • Extremely low doses of peripheral morphine can activate sensory nerve endings via MOP-R.
  • This activation triggers a cascade involving SP release and downstream signaling pathways, leading to a nociceptive response.

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