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ANESTHETIC PHARMACOLOGY

Chronic Subarachnoid Administration of 1-(4chlorobenzoyl)-5methoxy-2methyl-1H-indole-3 Acetic Acid (Indomethacin): An Evaluation of Its Neurotoxic Effects in an Animal Model

Uriah Guevara-López, MD^*, Alfredo Covarrubias-Gómez, MD^*, Hilario Gutierrez-Acar, MD^||, J. Antonio Aldrete, MD^#, Francisco J. López-Muñoz, PhD^¶, and Braulio Martínez-Benítez, MD

From the Departments of *Pain and Palliative Medicine and Pathology, National Institute for Medical Sciences and Nutrition "Salvador Zubirán"; Medical Unit of High Specialization (UMAE) Magdalena de las Salinas, IMSS; Department of Anesthesiology, National Institute of Rehabilitation; ||Department of Anesthesiology, General Hospital "Manuel Gea González"; ¶Laboratory No. 7 "Pain and Analgesia," Department of Pharmacobiology, Cinvestav-Coapa, Mexico City, Mexico; and #Department of Anesthesiology, University of Alabama at Birmingham.

Address correspondence and reprint requests to Guevara-López Uriah, MD, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán," Vasco de Quiroga # 15, Del. Tlalpan, CP 14000, México, D. F. México. Address e-mail to uriahguevara{at}yahoo.com.mx.

Neuraxial administration of nonsteroid antiinflammatory drugs has been suggested as an alternative in the management of intractable pain, but there is little evidence that the neurotoxic effects of indomethacin by this route of administration have been evaluated. In this study, we evaluated histological neurotoxicity of indomethacin after its subarachnoid administration in guinea pigs. The hypothesis tested was "Does subarachnoid administration of indomethacin produce damage in the spinal cord of guinea pigs?" Ten male guinea pigs were anesthetized, and a polyamide catheter connected to a subcutaneous osmotic micro-pump was implanted at the L2-3 level. Animals were randomly assigned in 2 groups of 5 animals each. Indomethacin or saline solution was administered by continuous infusion (0.5 µL/h) for 14 days. Neurotoxicity was determined by spinal cord histopathology. There was no evidence of toxicity in the histological examinations of either group. These data suggest that subarachnoid administration of indomethacin infusion, at these doses, did not produce lesions typical of neurotoxicity in the spinal cord. We have concluded that epidural administration of indomethacin may be considered an alternative for application in human pain management, although more studies to determine its safety are required.