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Anesth Analg 2006;102:283-287
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ane.0000183639.37428.4d

REGIONAL ANESTHESIA

Doxepin by Topical Application and Intrathecal Route in Rats

Peter Gerner, MD*, Venkatesh Srinivasa, MD*, Anthony M. Zizza, BA*, Zhi-Ye Zhuang, PhD*, ShiHua Luo, BS*, David Zurakowski, PhD{dagger}, Sunil Eappen, MD*, and GingKuo Wang, PhD*

*Pain Research Center, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical School; and {dagger}Department of Biostatistics, Department of Orthopaedic Surgery, Children’s Hospital and Harvard Medical School, Boston, Massachusetts

Address correspondence and reprint requests to Peter Gerner, MD, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115. Address e-mail to pgerner{at}partners.org.

The tricyclic antidepressant, doxepin, has been reported to be a potent local anesthetic in rat sciatic nerve blockade. We hypothesized that topical doxepin has significantly longer antinociception compared with control and intrathecally compared with bupivacaine. Solutions of 0.3 mL of doxepin at 50, 75, and 100 mM and control (only the vehicle solution) were applied as a patch to the shaved dorsal skin of rats. After a 2-h contact interval, the patch was removed, and the rats were tested by three sets of six pinpricks. Inhibition of withdrawal to pain and cutaneous trunci muscle reflex were graded. In the second investigation, 60 µL of doxepin at 10, 20, and 50 mM was injected through intrathecal catheters implanted in the lumbar region of rats, which were evaluated for motor function, proprioception, and nociception. Topical doxepin at concentrations of 75 mM and 100 mM was significantly more effective than control (P < 0.05). Complete recovery for the 100-mM concentration occurred at 60 h, although two of five rats demonstrated erythema and scarring. Intrathecally, 20 mM of doxepin was not significantly different for motor and proprioceptive function from 23 mM (0.75%) bupivacaine; however, neurotoxicity (defined as persistent neurological deficit) commenced at 50 mM.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2006 by the International Anesthesia Research Society.