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Updated: Aug 30, 2026

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

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

Published on: July 29, 2014

Spinally delivered N-, P/Q- and L-type Ca2+-channel blockers potentiate morphine analgesia in mice

Tadaoki Fukuizumi1, Tsuyako Ohkubo, Kenji Kitamura

  • 1Department of Physiological Science and Molecular Biology, Fukuoka Dental College, 2-15-1 Tamura, Sawara, Fukuoka 814-0193, Japan.

Life Sciences
|September 27, 2003
PubMed

Insights

Combining spinal voltage-dependent calcium channel (VDCC) blockers with morphine enhances pain relief. Specifically, N- and P/Q-type VDCC blockers significantly boosted morphine

Area of Science:

  • Neuroscience
  • Pharmacology
  • Pain Research

Background:

  • Voltage-dependent calcium channels (VDCCs) play a crucial role in pain signaling at the spinal level.
  • Morphine is a primary analgesic, but its efficacy can be limited by side effects and tolerance.

Purpose of the Study:

  • To investigate the antinociceptive effects of spinal N-, P/Q-, and L-type VDCC blockers, alone and in combination with morphine.
  • To determine if VDCC blockers can potentiate morphine's analgesic effects and potentially reduce required morphine dosage.

Main Methods:

  • Intrathecal administration of omega-agatoxin IVA (P/Q-type), omega-conotoxin GVIA (N-type), and calciseptine (L-type) VDCC blockers in mice.
  • Assessment of antinociception using tail-flick (thermal) and tail-pressure (mechanical) tests.
  • Evaluation of the combined effects of subthreshold doses of VDCC blockers with morphine.

Main Results:

  • Intrathecal omega-agatoxin IVA and omega-conotoxin GVIA demonstrated potent dose-dependent antinociception against both thermal and mechanical stimuli.
  • Omega-conotoxin GVIA showed stronger antinociception against mechanical stimuli compared to thermal stimuli.
  • Subthreshold doses of N- and P/Q-type VDCC blockers significantly enhanced morphine analgesia, with a potency order of N- or P/Q-type greater than or equal to L-type.

Conclusions:

  • Spinal N- and P/Q-type VDCC blockers exhibit significant antinociceptive properties.
  • Combining low doses of N- or P/Q-type VDCC blockers with morphine offers a promising strategy for potentiating analgesia.
  • This combination approach may allow for reduced morphine dosage, potentially mitigating associated side effects.

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