title: Midazolam can potentiate the analgesic effects of intrathecal bupivacaine on thermal- or inflammatory-induced pain.
abstract: 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.
  
  
  CONCLUSIONS
  In both acute thermal- and inflammatory-induced pain, intrathecally administered midazolam and bupivacaine produced synergistic analgesia with decreased side effects in intrathecally catheterized rats.
authors.affiliation: Department of Anesthesiology, The University of Tokyo, Tokyo, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Nishiyama
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hanaoka
mesh_terms: D018686:Anesthetics, Intravenous / Q000009:adverse effects / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002045:Bupivacaine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005557:Formaldehyde; D006358:Hot Temperature / Q000009:adverse effects*; D007249:Inflammation / Q000150:complications*; D007278:Injections, Spinal; D008297:Male; D008874:Midazolam / Q000009:adverse effects / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology*; D010147:Pain Measurement / Q000187:drug effects; D011595:Psychomotor Agitation / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018686:Anesthetics, Intravenous; D000779:Anesthetics, Local; D005557:Formaldehyde; D008874:Midazolam; D002045:Bupivacaine