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BJA Advance Access originally published online on August 20, 2008
British Journal of Anaesthesia 2008 101(5):716-722; doi:10.1093/bja/aen243
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© The Board of Management and Trustees of the British Journal of Anaesthesia 2008. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Intrathecal lidocaine elevates prostaglandin E2 levels in cerebrospinal fluid: a microdialysis study in freely moving rats{dagger}

V. Umbrain1,*, L. Shi2, M.-H. Lauwers1, I. Smolders3, Y. Michotte3 and F. Camu1

1 Department of Anaesthesiology and Pain Medicine, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, Belgium
2 J&J Pharmaceutical Research and Development, Beerse, Belgium
3 Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium

* Corresponding author. E-mail: vincent.umbrain{at}uzbrussel.be

Background: In this study, we have investigated whether intrathecal (i.t.) lidocaine administration is accompanied with changes of cerebrospinal fluid (CSF) prostaglandin E2 (PGE2) levels.

Methods: Rats were anaesthetized for i.t. implantation of a triple-lumen spinal loop dialysis catheter. CSF changes in PGE2 after i.t. injection of saline, 400, or 1000 µg of lidocaine were measured. The impact of i.t. pretreatment with 5 µg MK801 (N-methyl-D-aspartate glutamate antagonist) or 10 µg SC76309A (COX-2 inhibitor) was also investigated. CSF dialysates for measurement of PGE2 were collected for 4 h. During the whole procedure, motor and sensory blocks were evaluated. A separate group receiving i.t. lidocaine 400 µg (without dialysate sampling) was assessed for mechanical (Von Frey) and radiant heat pain.

Results: PGE2 levels increased to 400% of baseline and remained elevated for 90–120 min after i.t. lidocaine at both doses. Pretreatment with SC76309A and MK801 attenuated this increase. A 40 min period of enhanced pain response was observed after Von Frey filament stimulation during and after sensory and motor block recovery.

Conclusions: I.T. lidocaine (400 or 1000 µg) increases PGE2 levels in the CSF for 90–120 min along with a transient period of mechanical hyperalgesia after sensory and motor block recovery.

Keywords: measurement techniques, microdialysis; pharmacology, lidocaine; pharmacology, prostaglandins

{dagger} This work was partly presented as an oral abstract at the Annual Neuroscience Meeting of Washington on November 14, 2005.


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