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Minocycline can delay the development of morphine tolerance, but cannot reverse existing tolerance in the maintenance period of neuropathic pain in rats.

Publication ,  Journal Article
Zhang, X; Wang, J; Yu, T; Du, D; Jiang, W
Published in: Clin Exp Pharmacol Physiol
January 2015

Neuropathic pain is a challenge for physicians and basic science researchers, because it often does not respond to routine treatment. The administration of morphine has been considered one of the effective recommended treatments, but its wide application is limited because of the development of antinociceptive tolerance. In general, basic science studies focus on neuropathic pain and morphine tolerance separately. However, we tried to investigate the effect of microglial activation on morphine tolerance in spinal nerve ligation (SNL) rats during the maintenance period of neuropathic pain. This study produced the following results. The morphine tolerance model in neuropathic pain was established by repeated administration of morphine twice daily (10 mg/kg s.c) in the maintenance period of SNL rats. Minocycline, the microglial activation inhibitor, was given once daily (30 mg/kg, i.p.) at different time-points. The CD11b protein level was measured by western blot to monitor microglial activation. Rats' mechanical allodynia was assessed using the 50% paw withdrawal threshold, and the tail antinociception was determined using the percentage of the maximal possible antinociceptive effect. First, the repeated administration of morphine induced the development of antinociceptive tolerance during the maintenance period of neuropathic pain. Second, during the development of morphine tolerance, microglial activation, which is related to the analgesic effect of morphine, decreased in the first few days, but this pattern was reversed in the following days with the development of morphine tolerance. Third, the repeated administration of minocycline, a microglial activation inhibitor, did not influence the antinociceptive effect of a single dose of morphine. Fourth, the pre-administration of minocycline can delay the development of morphine tolerance, but repeated minocycline administration cannot reverse existing morphine tolerance. We concluded that microglial activation contributes to the morphine tolerance of SNL rats in the maintenance period of neuropathic pain, and that minocycline delays the development of morphine tolerance, but does not reverse existing morphine tolerance during the maintenance period of neuropathic pain in rats. These findings might be useful for clinical pain management.

Duke Scholars

Published In

Clin Exp Pharmacol Physiol

DOI

EISSN

1440-1681

Publication Date

January 2015

Volume

42

Issue

1

Start / End Page

94 / 101

Location

Australia

Related Subject Headings

  • Time Factors
  • Rats, Sprague-Dawley
  • Rats
  • Random Allocation
  • Physiology
  • Pain Measurement
  • Neuralgia
  • Morphine
  • Minocycline
  • Male
 

Citation

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Zhang, X., Wang, J., Yu, T., Du, D., & Jiang, W. (2015). Minocycline can delay the development of morphine tolerance, but cannot reverse existing tolerance in the maintenance period of neuropathic pain in rats. Clin Exp Pharmacol Physiol, 42(1), 94–101. https://doi.org/10.1111/1440-1681.12316
Zhang, Xin, Jing Wang, Tingting Yu, Dongping Du, and Wei Jiang. “Minocycline can delay the development of morphine tolerance, but cannot reverse existing tolerance in the maintenance period of neuropathic pain in rats.Clin Exp Pharmacol Physiol 42, no. 1 (January 2015): 94–101. https://doi.org/10.1111/1440-1681.12316.
Zhang, Xin, et al. “Minocycline can delay the development of morphine tolerance, but cannot reverse existing tolerance in the maintenance period of neuropathic pain in rats.Clin Exp Pharmacol Physiol, vol. 42, no. 1, Jan. 2015, pp. 94–101. Pubmed, doi:10.1111/1440-1681.12316.
Journal cover image

Published In

Clin Exp Pharmacol Physiol

DOI

EISSN

1440-1681

Publication Date

January 2015

Volume

42

Issue

1

Start / End Page

94 / 101

Location

Australia

Related Subject Headings

  • Time Factors
  • Rats, Sprague-Dawley
  • Rats
  • Random Allocation
  • Physiology
  • Pain Measurement
  • Neuralgia
  • Morphine
  • Minocycline
  • Male