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Cannabinoid-mediated diversity of antinociceptive efficacy of parecoxib in Wistar and Sprague Dawley rats in the chronic constriction injury model of neuropathic pain

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Abstract

We studied nociceptive behavior and the effects of analgesics in Wistar (Wist) and Sprague Dawley (SPD) rats and in CB1 receptor-deficient mice with neuropathic pain experimentally. Neuropathic pain was induced by loose ligation of the sciatic nerve (chronic constriction injury, CCI). In CCI rats from both strains, cold allodynia and a reduced thermal pain threshold were detected, whereas no effect was found in the hot plate test. Thermal pain threshold was used to study the antinociceptive effects of morphine, gabapentin, and parecoxib 5 days after surgery. Doses of gabapentin and morphine which had no effect on sham-operated animals provoked antinociceptive activity in CCI rats from both strains. An antinociceptive effect of parecoxib was only found in CCI Wist rats. No pharmacokinetic differences were detected between the two strains in parecoxib metabolism. Antinociceptive activity caused by parecoxib was attenuated by the CB1 antagonist rimonabant. To further clarify parecoxib—CB1 interaction, the effect of parecoxib was investigated in CB1-deficient mice and wild-type animals. CCI did not affect thermal pain threshold and mechanical pain threshold was decreased. Parecoxib normalized the altered mechanical pain threshold in CCI wild-type animals, whereas it had only a marginal effect in CB1 receptor deficient mice. Receptor binding experiments showed increased CB1 binding in parecoxib-treated CCI Wist rats. Levels of the CB1 receptor mRNA remained constant in both strains of rats 5 days after surgery. Differences in antinociceptive activity might be due to modification of the cannabinoid system.

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Acknowledgments

The authors wish to thank Michaela Böx, Petra Dehmel, Cathleen Knape, Dana Meyer, Gabriele Schulze, Helga Tischmeyer, and Carlo Angioni for their expert technical assistance.

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The authors have no conflicts of interest related to this research.

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Authors and Affiliations

  1. Faculty of Medicine, Institute of Pharmacology and Toxicology, O. v. Guericke University, Leipziger Strasse 44, 39120, Magdeburg, Germany

    Axel Becker, Radovan Murín, Gisela Grecksch, Volker Höllt & Helmut Schröder

  2. Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Theodor-Stern-Kai 7, 60590, Frankfurt-am-Main, Germany

    Gerd Geisslinger

  3. Institute of Molecular Psychiatry, University of Bonn, Sigmund-Freud-Str. 25, 531257, Bonn, Germany

    Andreas Zimmer

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  1. Axel Becker
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  2. Gerd Geisslinger
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  3. Radovan Murín
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Correspondence to Axel Becker.

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Becker, A., Geisslinger, G., Murín, R. et al. Cannabinoid-mediated diversity of antinociceptive efficacy of parecoxib in Wistar and Sprague Dawley rats in the chronic constriction injury model of neuropathic pain. Naunyn-Schmiedeberg's Arch Pharmacol 386, 369–382 (2013). https://doi.org/10.1007/s00210-013-0839-2

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