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TECHNOLOGY, COMPUTING, AND SIMULATION

Intrathecal Catheterization and Solvents Interfere with Cortical Somatosensory Evoked Potentials Used in Assessing Nociception in Awake Rats

Lin Shi, MD^*,, Philippe Lebrun, MD PhD, Frederic Camu, MD PhD^*, and Martin Zizi, MD PhD

Departments of *Anesthesiology and Physiology, Faculty of Medicine, Free University of Brussels, Brussels, Belgium

Address correspondence and reprint requests to Martin Zizi, MD, PhD, Department of Physiology, Free University Brussels Medical School, 103 Laarbeeklaan, 1090 Brussels, Belgium. Address e-mail to martin.zizi{at}vub.ac.be

We assessed the objective measurement of central sensitization processes in the awake rat after subcutaneous formalin with cortical somatosensory evoked potentials (CSEPs). Cranial extradural electrodes and intrathecal catheters were implanted in adult male Wistar rats. After 7 days of recovery, CSEPs were induced by electrical stimuli at the tail and recorded before/after the injection of 50 µL of 2% formalin into the hindpaw of rats for 1 h. The drug and tested vehicles were delivered intrathecally 5 min before the injection of formalin. The peak-to-peak amplitude of the P1-N1 (the early positive-negative sequence pair of CSEPs) and the baseline-to-peak amplitude of the N2 (the late negative component of CSEPs) were analyzed. We found that the amplitudes of both signals increased (154.3% ± 10.9% and 168.7% ± 9.8%, respectively) from 10 min after formalin injection to the end of the 60-min test period. Pretreatment with intrathecal ketorolac dose-dependently prevented the increases induced by formalin in both measured variables. Moreover, the increases in P1-N1 and N2 were markedly attenuated either by intrathecal polyethylene-10 tubing or by the solvents used for injection, thus indicating the need for distinguishing an impaired nociceptive signal from antinociception when the effects of drugs are evaluated.

IMPLICATIONS: Variability is the main limitation of cortical somatosensory evoked potential (CSEP) measurements. This study validated CSEPs to examine central sensitization induced by formalin. Testing conditions were found in which CSEP signals could be reliably used to evaluate central sensitization processes, as well as the antinociceptive effect of the drug, in a dose-dependent manner.