This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Nishiyama, T. Articles by Hanaoka, K. Search for Related Content PubMed PubMed Citation Articles by Nishiyama, T. Articles by Hanaoka, K. Related Collections Pain Pharmacology

---

PAIN MEDICINE

Midazolam Can Potentiate the Analgesic Effects of Intrathecal Bupivacaine on Thermal- or Inflammatory-Induced Pain

Department of Anesthesiology, The University of Tokyo, Tokyo, Japan

Address correspondence and reprint requests to Tomoki Nishiyama, MD, PhD, 3-2-6-603, Kawaguchi, Kawaguchi-shi, Saitama, 332-0015, Japan. Address e-mail to nishiyamat-ane{at}h.u-tokyo.ac.jp

Epidurally administered midazolam can potentiate analgesia by epidural bupivacaine. However, whether this effect is synergistic or additive is not known. In this study, we investigated the spinally-mediated analgesic interaction between midazolam and bupivacaine by using the tail-flick and formalin tests in rats with chronically implanted catheters. Behavioral effects were also observed. The dose dependency of analgesia and the 50% effective doses of intrathecal midazolam and bupivacaine were determined, and then the interaction of these two drugs was examined with an isobolographic analysis. Both drugs had dose-dependent analgesic effects in both the tail-flick test and the formalin test. The 50% effective dose values of the combination were significantly lower than the calculated additive values in both tests (P = 0.023 in the tail-flick test; P = 0.0025 in Phase 1 and 0.047 in Phase 2 of the formalin test). Behavioral side effects decreased in the combination group compared with each drug alone. In conclusion, intrathecally administered midazolam and bupivacaine had synergistic analgesic effects on acute thermal- or inflammatory-induced pain, with decreased behavioral side effects.

IMPLICATIONS: In both acute thermal- and inflammatory-induced pain, intrathecally administered midazolam and bupivacaine produced synergistic analgesia with decreased side effects in intrathecally catheterized rats.

This article has been cited by other articles:

				S. Kang, C. H. Kim, H. Lee, D. Y. Kim, J. I. Han, R. K. Chung, and G. Y. Lee Antinociceptive Synergy Between the Cannabinoid Receptor Agonist WIN 55,212-2 and Bupivacaine in the Rat Formalin Test Anesth. Analg., March 1, 2007; 104(3): 719 - 725. [Abstract] [Full Text] [PDF]

				T. L. Yaksh and J. W. Allen The Use of Intrathecal Midazolam in Humans: A Case Study of Process Anesth. Analg., June 1, 2004; 98(6): 1536 - 1545. [Abstract] [Full Text] [PDF]