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 We assessed the objective measurement of central sen- sitization processes in the awake rat after subcutaneous formalin with cortical somatosensory evoked poten- tials (CSEPs). Cranial extradural electrodes and intra- thecal 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 L of 2% formalin into the hindpaw of rats for 1 h. The drug and tested vehicles were deliv- ered 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 for- malin injection to the end of the 60-min test period. Pre- treatment 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 in- jection, thus indicating the need for distinguishing an impaired nociceptive signal from antinociception when the effects of drugs are evaluated. (Anesth Analg 2004;99:159 –65) B ecause of their relevance in various clinical settings, objective methods for measuring no- ciception have generated a broad interest among scientists and medical personnel involved in pain research or pain management. Whereas the quantitative assessment of nociception can be ad- dressed by various invasive electrophysiological methods (1,2), the evaluation of pain in unanesthe- tized animals relies almost exclusively on behav- ioral testing (3). An electrophysiological method based on a tonic pain model in awake animals would allow a more reliable interpretation of the data and would offer finer pharmacological testing conditions. Cortical somatosensory evoked potentials (CSEPs) are objective records of activity evoked in neural path- ways by a given stimulus. CSEPs correlate with noci- ception in humans (4 – 6) and in an anesthetized ani- mal pain model (7). We previously demonstrated the use of CSEPs as an objective measurement of central excitability after subcutaneous (SC) injection of forma- lin at the base of the tail in the awake rat (8). Two major components of the electrical signal were identi- fied: an early positive-negative (P1-N1) sequence re- lated to the arrival of the afferent volley in the cortex and a more ample late negative (N2) component that presumably arose from associative signal postprocess- ing. The amplitudes of both CSEP components evoked by nonnoxious stimuli were equally increased after the injection of formalin and were considered to be related to the central sensitization induced by forma- lin, because the stimuli given to elicit the CSEPs were distant from the site of injection. In attempts to eval- uate the effects of intrathecal drugs on formalin- induced central processing by using CSEPs, we found that increased CSEPs were markedly altered by rou- tine polyethylene (PE)-10 catheterization and by the varieties of solvents used for dissolving drugs. Intra- thecal injection of the solvents themselves even in- duced agitation and squeaking in the animals. Al- though it is reported in some publications (9 –12), not This work was supported by the Research Grant Program of the Society for Anesthesia and Resuscitation of Belgium (LS) and Grant RSTD-WB-03 from the Department of Defense. LS is supported by a Free University Brussels fellowship. MZ is supported by the Belgian Department of Defense. Accepted for publication December 10, 2003. 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@vub.ac.be. DOI: 10.1213/01.ANE.0000114552.20268.7F ©2004 by the International Anesthesia Research Society 0003-2999/04 Anesth Analg 2004;99:159–65 159