1 Department of Trauma Surgery and Sports Medicine, 2 Department of Anaesthesia and Intensive Care Medicine, 3 Department of Magnetic Resonance Imaging, 4 Department of Vascular Surgery and 5 Department of Pathology, University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria
*Corresponding author. E-mail: heinrich.schubert@uibk.ac.at
Accepted for publication: June 29, 2003
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Abstract |
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Methods. We constructed a computer-controlled pneumatic device to apply pressure to the anterior tibia. The reproducibility of the pain was tested by rating the pressure that caused pain rated 45 on a visual analogue scale (VAS) on days 0, 7, and 24 in 10 volunteers. The effect of remifentanil (0.025, 0.05, 0.075, and 0.1 µg kg1 min1) on pain tolerance in another set of volunteers (n=11) was used as an indirect measure of the reliability of pain production.
Results. The pressure needed (0.7 (0.3) to 0.9 (0.4) atm (mean (SD)) to induce pain rated 45 (VAS) did not vary, showing long-term reproducibility of the method. When pressure was applied to cause increasing pain in volunteers (n=11) 0.05 µg kg1 min1 remifentanil increased pain tolerance by 50%. An approximate doubling of the dose (0.1 µg kg1 min1) increased pain tolerance significantly more. The linear logarithmic dose-effect relationship shows that the device causes pain reliably, and this can be reduced with opioid treatment.
Conclusion. This pneumatic device can apply pain reliably and reproducibly.
Br J Anaesth 2004; 92: 5325
Keywords: analgesics opioid, remifentanil; pain, experimental; pain, stimulus; pain, tolerance; volunteers
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Introduction |
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We constructed a pneumatic device to reliably and reproducibly apply a painful stimulus, with computer control of intensity and duration. We measured reproducibility from the pressure needed to induce pain of a set subjective intensity (4 or 5 on a visual analogue scale (VAS)) on three occasions 7 and 24 days apart. We assessed reliability using a remifentanil infusion where the doseeffect relationship is known.
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Methods |
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Non-magnetizable materials were used to construct the device. To test the suitability of the device for fMRI measurements we made MRI phantom measurements, separate from the volunteer studies.
Experimental protocol
After approval by the local University Ethics Committee and with written informed consent, we enrolled 21 right-handed, non-smoking, healthy, male volunteers (ASA physical status I) with no history of chronic medication or drug or alcohol abuse.
Reproducibility of pain stimulus (10 subjects)
To test the reproducibility of the pain stimulus, the device was fixed to the anterior margin of the left tibia 10 cm above the ankle. We applied enough pressure to cause pain that was rated 45 on a VAS of 011. The pressure exerted was recorded on the first occasion and repeated after 7 and 24 days.
Reliability of pain stimulus (11 subjects)
The reliability of pain stimulus was tested by studying the effect of remifentanil (0.025, 0.05, 0.075, and 0.1 µg kg1 min1) on pain tolerance (per cent of maximum possible effect (%MPE); for details see Statistical analysis). The device was fixed as before. We set it to deliver a pressure, which increased by 0.2 atm every 5 s. The volunteers were instructed to switch off the device when the pain became intolerable. The time before the device was turned off was taken as the measure of pain tolerance. To prevent possible tissue damage the cut-off time for pressure application was set at 90 s and the cut-off pressure at 3 atm.
Following control measurement of pain tolerance, a continuous infusion of remifentanil was started. Each continuous infusion rate was preceded by a loading dose, where the infusion rate was increased by 25% for a period of 5 min. After an additional 15 min infusion of remifentanil, pain tolerance was measured. The doses were tested in ascending order, at 0.025, 0.05, 0.075, and 0.1 µg kg1 min1. The remifentanil infusion was then discontinued and a final control measurement was made 20 min later.
Statistical analysis
The time before the device was turned off is expressed as %MPE. The effect of the drug on the time for which pain is tolerated is expressed as a percentage of the maximum acceptable increase in toleration.
%MPE was calculated as follows:
where predrug time=time pain was tolerated before drug administration; postdrug time=time pain was tolerated during drug administration.
Data are given as mean (SD) or, for age, mean (range) and descriptive data analysis was used. As the KolmogorovSmirnov test showed normal distribution of data, analysis of variance (ANOVA) for repeated measurements with Least-Square Difference (LSD) correction for multiple testing was done to compare %MPE at the various doses of remifentanil. A P0.05 was considered statistically significant. The 50% MPE dose was interpolated from the doseeffect curves measured for remifentanil.
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Results and comment |
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Nausea, vomiting, or even respiratory depression are known side effects in patients given remifentanil for postoperative analgesia (0.0250.15 µg kg1 min1).16 These did not occur in our volunteers (n=11; age 27(4) yr; weight 79 (11) kg; height 182 (6) cm).
The materials used for construction of the cuff with the thumper and tubing were MRI-suitable, shown by an additional (non-volunteer) MRI phantom measurement (results not published). The pneumatic pressure pain device is suitable for fMRI studies on cerebral pain processing, which was a requirement for the device.
In conclusion, we constructed a computer-controlled pneumatic device to apply a painful stimulus, which is reliable and reproducible.
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Acknowledgement |
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References |
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