Interaction of physostigmine and alfentanil in a human pain model.
BACKGROUND
Preclinical and clinical studies suggest an important role for cholinesterase inhibitors in pain therapy. The aim of this study was to examine the analgesic and antihyperalgesic properties of the cholinesterase inhibitor physostigmine and the opioid alfentanil, alone and in combination, in an experimental pain model in humans.


METHODS
Twenty healthy volunteers were enrolled in this double-blind and placebo-controlled cross-over study. Transcutaneous electrical stimulation at high current densities induced spontaneous acute pain and stable areas of hyperalgesia for painful mechanical stimuli (pinprick-hyperalgesia). Pain intensities, measured on a numeric rating scale (NRS) from 0 to 10, and the extent of the hyperalgesic areas were assessed before, during, and 145 min after i.v. infusions of physostigmine (30 microg kg(-1) in 15 min), alfentanil (20 microg kg(-1) in 2 min), the combination of the same doses of both drugs, or saline 0.9%. The type of interaction was determined by fitting an interaction model to the data.


RESULTS
Starting from a baseline value of NRS=6, the maximum reduction of pain intensity was 50.4 (sd 22.3) % after alfentanil, 35.4 (20.0) % after physostigmine, and 60.4 (17.1) % after the combination. The hyperalgesic areas were reduced by 53.8 (33.2) %, 47.0 (26.3) %, and 54.8 (33.2) %, respectively. The data were best described by a model assuming an infra-additive interaction for analgesic and antihyperalgesic effects.


CONCLUSIONS
Physostigmine and alfentanil showed distinct effects on pain and hyperalgesia in a human pain model. The interaction of both drugs was found to be infra-additive.
Wehrfritz
A P
AP
Department of Anaesthesiology, University Hospital Erlangen, Krankenhausstrasse 12, D-91054, Erlangen, Germany.
Ihmsen
H
H
Schmidt
S
S
Müller
C
C
Filitz
J
J
Schüttler
J
J
Koppert
W
W
D000208:Acute Disease; D000328:Adult; D015760:Alfentanil / Q000008:administration & dosage / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008954:Models, Biological; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000379:methods; D010830:Physostigmine / Q000008:administration & dosage / Q000627:therapeutic use*; D055815:Young Adult
D000701:Analgesics, Opioid; D002800:Cholinesterase Inhibitors; D015760:Alfentanil; D010830:Physostigmine