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 (D MSO)-containing morphine produces a dose-dependent, naloxone-sensitive, ana lgesia (ED50 6.1 mM; CL 4.3, 8.4) limited to the portion of the tail expose d to the drug. DMSO alone in this paradigm had no analgesic activity. Like morphine, the opioids levorphanol (ED50 5.0 mM; CL 3.8, 7.8) and buprenorph ine (ED50 1.1 mM; CL 0.7, 1.5) were effective topical analgesics. Lidocaine also was active in the tail-flick assay (ED50 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 f or all opioids tested. Isobolo-graphic analysis confirmed the presence of s ynergy 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 managemen t of pain.