Background: Understanding analgesic pharmacodynamics (PD) in the elderly is key to optimising
pain management. Electrically stimulated pain models (ESPM) permit assessment of pain responses
in humans. C and Aδ sensory fibres convey pain and respond to low frequency electrical stimulus
(5 and 250 Hz, respectively). Human research suggests pain tolerance threshold (PTT) is similar or
decreases with age.
Objectives: To determine whether an ESPM is able to detect a difference in PTT in elderly (≥
75 years) and young (20-40 years) subjects after single dose administration of a placebo and
tramadol, a low potency analgesic.
Study Design: Two-cohort, randomized, placebo-controlled, cross-over study.
Methods: A noncompartmental analysis of data at 17 timepoints on 5 Hz and 250 Hz PTT over
24 h.
Results: Young (16) and elderly (13) patients showed similar baseline (E0) PTT between active
and placebo both overall and by age group in both frequencies. Net drug effect took into account
negative and positive changes from E0. In the elderly, net peak effect on PTT produced by active
treatment was significantly greater for both 5 Hz (34%) and 250 Hz (30%). Net area under the
24-h effect-time curve during active treatment was significantly higher for both 5 Hz (163 %) and
250 Hz (175%) stimulations in the elderly. No clinically significant difference was observed in the
young.
Limitations: High variability in young subjects, despite efforts to remove outliers limited
our ability to draw conclusions in that age group. Generalizability of results obtained from an
experimental pain model in volunteers to treatment of elderly patients may be limited.
Conclusion: ESPM can detect a difference for pain tolerance threshold between placebo and
tramadol administration in the elderly. Although both 5 Hz and 250 Hz stimulations can detect a
difference, the effect size for 5 Hz is larger and seems more precise and reliable, particularly in the
elderly.
Key words: Electrical pain model, elderly, geriatric, tramadol, placebo, opioid, area under the
effect curve, noncompartmental analysis
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