Analgesic Synergy between Topical Lidocaine and Topical Opioids

Topical drugs avoid many of the problematic side effects of systemic agents. Immersion of the tail of a mouse into a solution of dimethyl sulfoxide (DMSO)-containing morphine produces a dose-dependent, naloxone-sensitive, analgesia (ED 50 6.1 mM; CL 4.3, 8.4) limited to the portion of the tail expos...

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Bibliographic Details
Published in:The Journal of pharmacology and experimental therapeutics 2000-11, Vol.295 (2), p.546
Main Authors: Kolesnikov, Y A, Chereshnev, I, Pasternak, G W
Format: Article
Language:English
Subjects:
Administration, Topical
Analgesics, Opioid - pharmacology
Anesthetics, Local - pharmacology
Animals
Buprenorphine - pharmacology
Dose-Response Relationship, Drug
Drug Synergism
Levorphanol - pharmacology
Lidocaine - pharmacology
Male
Mice
Mice, Inbred ICR
Morphine - pharmacology
Pain Measurement - drug effects
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Summary:Topical drugs avoid many of the problematic side effects of systemic agents. Immersion of the tail of a mouse into a solution of dimethyl sulfoxide (DMSO)-containing morphine produces a dose-dependent, naloxone-sensitive, analgesia (ED 50 6.1 mM; CL 4.3, 8.4) limited to the portion of the tail exposed to the drug. DMSO alone in this paradigm had no analgesic activity. Like morphine, the opioids levorphanol (ED 50 5.0 mM; CL 3.8, 7.8) and buprenorphine (ED 50 1.1 mM; CL 0.7, 1.5) were effective topical analgesics. Lidocaine also was active in the tail-flick assay (ED 50 2.5 mM; CL 2.0, 3.4), with a potency greater than morphine. As expected, the free base of lidocaine was more potent than its salt. Combinations of a low dose of lidocaine with a low dose of an opioid yielded significantly greater than additive effects for all opioids tested. Isobolographic analysis confirmed the presence of synergy between lidocaine and morphine, levorphanol and buprenorphine. These studies demonstrate a potent interaction peripherally between opioids and a local anesthetic and offer potential advantages in the clinical management of pain.
ISSN:0022-3565
1521-0103