title: Effects of Different Anesthetics on Pain Processing in an Experimental Human Pain Model.
abstract: After surgical procedures, anesthesia itself may affect pain perception. Particularly, there is increasing evidence that opioids not only have analgesic effects but also provoke pronociceptive changes, that is, opioid-induced hyperalgesia. We investigated the effect of different anesthetic regimens on pain processing in volunteers using a transdermal electrical pain model. In this model, stimulation of epidermal nerve fibers representing mainly peptidergic C-nociceptors leads to secondary hyperalgesia and habituation to the stimulus.
  
  
  
  Forty-eight healthy volunteers underwent conditioning noxious stimulation (CS) over 5 days. On day 2, the volunteers were randomized into 4 groups: control group (no anesthesia) and 3 groups receiving anesthesia before CS in anesthetic doses: propofol (P), propofol/remifentanil (PR), and propofol/remifentanil/S-ketamine (PRK). Quantitative sensory testing was performed on days 1 through 5 and on day 22.
  
  
  
  In every group, CS was associated with short- and long-term habituation to the electrical stimulus. Repetitive CS resulted in unmodified short-term sensitization with stable areas of hyperalgesia. Although the PR group showed a trend toward increased areas of hyperalgesia on day 2, no significant differences were detectable between the groups. In contrast, anesthesia resulted in decreased intensity of the electrically evoked pain on day 2. Finally, the mechanical pain threshold before CS on day 5 was increased in all groups and remained elevated 3 weeks after the first CS, consistent with a long-term antinociceptive effect after CS.
  
  
  
  The results suggest a short-term analgesic effect of general anesthesia. Furthermore, the conditioning stimulation over several days induced differential modulation of pro- and antinociceptive systems.
authors.affiliation: Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.|Department of Neurology, General Fürth Hospital, Fürth, Germany.
authors.forename: Florian T
authors.initials: FT
authors.lastname: Nickel
authors.affiliation: Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Ott
authors.affiliation: Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Möhringer
authors.affiliation: Department of Anesthesiology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Tino
authors.initials: T
authors.lastname: Münster
authors.affiliation: Department of Anesthesiology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Rieß
authors.affiliation: Department of Anesthesiology, Hannover Medical School, Hannover, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Filitz
authors.affiliation: Department of Anesthesiology, Hannover Medical School, Hannover, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koppert
authors.affiliation: Department of Neurology, General Fürth Hospital, Fürth, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Maihöfner
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology; D000777:Anesthetics / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced* / Q000503:physiopathology; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D010146:Pain / Q000188:drug therapy; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology; D000077208:Remifentanil; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D000777:Anesthetics; D010880:Piperidines; D007649:Ketamine; D000077208:Remifentanil; D015742:Propofol
keywords: N-methyl-d-aspartate antagonism; NMDA; conditioning stimulation; experimental pain model; general anesthesia; human pain model; pain processing