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Repeated Administration of Baclofen Modulates TRPV-1 Channel Expression by PKC Pathway in Dorsal Root Ganglia of Spinal Cord in a Morphine Tolerance Model of Rats

Authors
  • Mehrabadi, Shima1
  • Karimiyan, Seyed Morteza1
  • Ashabi, Ghorbangol1
  • Moradbeygi, Khadijeh1, 2
  • Hoseini, Marjan1
  • 1 Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;
  • 2 Department of Nursing, Abadan Faculty of Medical Sciences, Abadan, Iran
Type
Published Article
Journal
Iranian Biomedical Journal
Publisher
Pasteur Institute of Iran
Publication Date
Jun 21, 2020
Volume
24
Issue
6
Pages
379–385
Identifiers
DOI: 10.29252/ibj.24.6.374
PMID: 32660223
PMCID: PMC7601548
Source
PubMed Central
Keywords
License
Green

Abstract

Background: Tolerance and dependence to anti-nociceptive effect of morphine restricted its use. Nowadays co-administration of morphine and other drugs suggests diminishing this tolerance. Baclofen is one of the drugs that may be beneficial in the attenuation of tolerance to morphine. Studies have shown that changes in TRPV-1 expression during administration of morphine have a pivotal role in developing morphine tolerance. Therefore, the effect of baclofen on TRPV-1 expression during chronic administration of morphine was investigated in this study. Methods: A total of 48 rats were divided into four groups of control, morphine single injection, morphine tolerance, and morphine tolerance + baclofen. To induce morphine tolerance in rats, animals received 10 mg/kg of i.p. morphine sulfate once a day for 10 days. In the treatment group, baclofen (0.5 mg/kg) was injected for 10 days, before morphine injection. Finally, to evaluate baclofen treatment on morphine analgesia and hyperalgesia, thermal hyperalgesia and formalin test were used. TRPV-1 and PKC expression and protein production in DRG of spinal cord were then evaluated by real-time PCR and Western blot. Results: In baclofen treatment group, thermal hyperalgesia and formalin test improved in comparison with morphine tolerance group. In morphine tolerance group, both TRPV-1/PKC gene expression and protein levels increased in comparison with the control group. However, following the baclofen treatment, the TRPV-1 and PKC levels decreased. Conclusion: Baclofen can enhance anti-nociceptive effect of morphine by modulating TRPV-1 channel and PKC activity.

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