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Licensed Unlicensed Requires Authentication Published by De Gruyter July 1, 2017

Effect of intrathecal glucocorticoids on the central glucocorticoid receptor in a rat nerve ligation model

Mienke Rijsdijk, Nilesh M. Agalave, Albert J.M. van Wijck, Cornelis J. Kalkman, Roshni Ramachandran, Azar Baharpoor, Camilla I. Svensson and Tony L. Yaksh

Abstract

Background and aims

Despite widespread use, the efficacy of neuraxial glucocorticoids for neuropathic painis subject to debate. Since most glucocorticoid actions are mediated through its receptor, we explored the effects of intrathecal methylprednisolone acetate (MPA) on total glucocorticoid receptor (tGR) levels and activation of the glucocorticoid receptor (phosphorylated state = pGR) within the spinal dorsal horn (SDH) and dorsal root ganglion (DRG) in a spinal nerve ligation (SNL) model in rats.

Methods

Rats received unilateral ligation of the L5/L6 spinal nerves and were treated with two intrathecal doses of either 400 μg MPA or 0.9% saline with a 72-h interval. Plantar tactile thresholds were measured over time. Seven days after drug treatment, DRG and SDH were harvested to assess tGR and pGR levels using immunohistochemistry and qPCR.

Results

Allodynia, defined by lowered tactile withdrawal thresholds after SNL, was unaltered by intrathecal MPA. In saline controls, mRNA levels of tGR did not change after SNL in the DRGs or SDH. tGR and pGR protein levels in the SDH however, significantly increased on the ipsilateral side of SNL compared to the contralateral side and to naïve tissue. When treating rats with MPA, tGR mRNA levels were significantly reduced in the SDH compared to saline controls. tGR and pGR protein levels, however were not significantly lower compared to saline controls.

Conclusions

In intrathecal MPA treated rats, tGR mRNA levels decreased after SNL. However this did not result in lower tGR and pGR protein levels compared to saline controls, and did not decrease ligation-induced mechanical hypersensitivity.

Implications

Intrathecal MPA treatment after SNL did not result in lower tGR and pGR levels within the SDH and DRG compared to saline controls. In present study we did not differentiate between the various isoforms of the GR which might clarify this finding.


DOI of refers to article: http://dx.doi.org/10.1016/j.sjpain.2017.03.003.



Pain Clinic, Department of Anesthesiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.

  1. Conflict of interest: None.

  2. Authors’ contribution: M. Rijsdijk performed the research, R. Ramachandran, N.M. Agalave and A. Baharpoor participated in data collection, M Rijsdijk, T.L. Yaksh and C.I. Svensson designed the research study, C.I. Svensson, C.J. Kalkman and T.L. Yaksh contributed essential reagents and tools, M. Rijsdijk, C.I. Svensson, A.J.M. van Wijck, C.J. Kalkman and T.L. Yaksh analyzed the data, M. Rijsdijk wrote the paper and C.I. Svensson, A.J.M. van Wijck, C.J. Kalkman, R. Ramachandran, N.M. Agalave and T.L. Yaksh revised the manuscript. All authors approved the final manuscript.

Acknowledgments

This study was funded by a collaborative research grant from the European Society of Regional Anesthesia and Pain Therapy, the Stiftelsen Lars Hiertas minne grant (FO2013-0235) from the Karolinska Institutet and the Department of Anesthesiology, University Medical Center, Utrecht, The Netherlands. Funders did not play a role designing the study, analyzing the data or preparing the manuscript. We thank Jorrit Huisman for his technical support with the illustrations.

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Received: 2016-04-03
Revised: 2016-12-30
Accepted: 2016-12-31
Published Online: 2017-07-01
Published in Print: 2017-07-01

© 2017 Scandinavian Association for the Study of Pain