title: Perineural dexmedetomidine added to ropivacaine for sciatic nerve block in rats prolongs the duration of analgesia by blocking the hyperpolarization-activated cation current.
abstract: BACKGROUND
  The current study was designed to test the hypothesis that the increased duration of analgesia caused by adding dexmedetomidine to local anesthetic results from blockade of the hyperpolarization-activated cation (I(h)) current.
  
  
  METHODS
  In this randomized, blinded, controlled study, the analgesic effects of peripheral nerve blocks using 0.5% ropivacaine alone or 0.5% ropivacaine plus dexmedetomidine (34 μM or 6 μg/kg) were assessed with or without the pretreatment of α(1)- and α(2)-adrenoceptor antagonists (prazosin and idazoxan, respectively) and antagonists and agonists of the I(h) current (ZD 7288 and forskolin, respectively). Sciatic nerve blocks were performed, and analgesia was measured by paw withdrawal latency to a thermal stimulus every 30 min for 300 min postblock.
  
  
  RESULTS
  The analgesic effect of dexmedetomidine added to ropivacaine was not reversed by either prazosin or idazoxan. There were no additive or attenuated effects from the pretreatment with ZD 7288 (I(h) current blocker) compared with dexmedetomidine added to ropivacaine. When forskolin was administered as a pretreatment to ropivacaine plus dexmedetomidine, there were statistically significant reductions in duration of analgesia at time points 90-180 min (P < 0.0001 for each individual comparison). The duration of blockade for the forskolin (768 μM) followed by ropivacaine plus dexmedetomidine group mirrored the pattern of the ropivacaine alone group, thereby implying a reversal effect.
  
  
  CONCLUSIONS
  Dexmedetomidine added to ropivacaine caused approximately a 75% increase in the duration of analgesia, which was reversed by pretreatment with an I(h) current enhancer. The analgesic effect of dexmedetomidine was not reversed by an α(2)-adrenoceptor antagonist.
authors.affiliation: Department of Anesthesiology, Division of Pain Medicine, University of Michigan, Ann Arbor, Michigan, USA. cbrummet@umich.edu
authors.forename: Chad M
authors.initials: CM
authors.lastname: Brummett
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Hong
authors.forename: Allison M
authors.initials: AM
authors.lastname: Janda
authors.forename: Francesco S
authors.initials: FS
authors.lastname: Amodeo
authors.forename: Ralph
authors.initials: R
authors.lastname: Lydic
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology*; D000698:Analgesia; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000037:antagonists & inhibitors*; D020927:Dexmedetomidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D019329:Idazoxan / Q000494:pharmacology; D008297:Male; D009407:Nerve Block; D010147:Pain Measurement / Q000187:drug effects; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011224:Prazosin / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077212:Ropivacaine; D012584:Sciatic Nerve / Q000187:drug effects*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000577:Amides; D000779:Anesthetics, Local; D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D006993:Hypnotics and Sedatives; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011743:Pyrimidines; C082246:ICI D2788; D005576:Colforsin; D020927:Dexmedetomidine; D000077212:Ropivacaine; D011224:Prazosin; D019329:Idazoxan