Background & Aims

50 million people worldwide had Alzheimer’s disease (AD) in 2020. Neuropathological changes associated with AD may alter pathways associated with the sensory (lateral) and affective (medial) dimensions of pain. Our group’s prior psychophysical studies suggest that individuals with AD may experience decreased or unchanged sensory pain intensity but greater pain unpleasantness compared to matched cognitively-intact controls. Our previous perceptual matching studies identified the temperature needed to achieve pain percepts of “just noticeable pain,” “mild pain,” and “moderate pain.” In this design, every patient experienced a different stimulus intensity and pain unpleasantness was rated in response to these varying stimuli, potentially confounding pain unpleasantness measures particularly. The purpose of this pilot study was to compare ratings of pain intensity and unpleasantness in individuals with and without AD in response to three fixed-temperature stimuli.

Methods

Older adults with and without AD were recruited from the community and an academic medical center’s geriatric or neurology faculty practices. Participants could communicate verbally, had capacity for consent assessed, and took no analgesic medicine for 24 hours prior to testing. Demographic information was collected as well as measures of depression (Geriatric Depression Scale-Short Form (GDS-SF)) and pain (Brief Pain Inventory Short Form (BPI-SF)). Thermal stimuli were administered with the Medoc Pathway Pain and Sensory Evaluation System®. Starting at 30ºC with a ramp rate of 4°C/second, participants were exposed to each of three fixed target temperatures (34, 39, and 44°C) for 10 seconds in a pseudorandom order. During the stimulus, participants provided verbal reports of pain intensity and unpleasantness, each on 0–20-point numeric rating scale. We used mixed-effects models with robust standard errors to test the effects of group and pain level on intensity and unpleasantness.

Results

A sample of older adults (N=82, median age 76.5 years, 58.5% female), including 21 with AD (median age 76.0 years, 52.4% female), were enrolled. An age/sex-matched control group was selected from the healthy controls for comparison with the AD group; There were no statistically significant differences between AD and control groups in standardized measures (GDS-SF, p=.15; BPI-SF average pain, p=.47; BPI-SF pain right now, p=.36). There was a statistically significant interaction effect of group and fixed temperature exposures on pain intensity (p=.03) though not with respect to reports of unpleasantness (p=.09). Contrasts within the mixed-effects model of intensity revealed that a significant change in intensity from 34 to 39°C was observed for the controls but not for the AD. A sensitivity model including all controls (N=61) replicated the interaction effects on intensity using statistical controls for age, sex, and GDS-SF score.

Conclusions

These findings suggest that when using a fixed stimulus psychophysical protocol, individuals with AD report lower pain intensity than cognitively-intact controls, but only for more intense stimuli. AD-related elevations in pain unpleasantness reported in our prior work using individualized percept-based heat pain stimuli were not replicated using the current fixed stimulus methodology, although a nonsignificant directional trend was noted. A larger sample size may be needed to detect smaller AD-related effects on unpleasantness. Alternatively, our past findings suggesting elevated affective pain responsiveness in those with AD may have been an artifact of the individualized percept-based methodology used in those studies. The current findings suggest an alternative methodology for psychophysical pain studies in AD in which pain unpleasantness is not confounded by individualized stimulus intensities.

References

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Presenting Author

Jeffrey Boon

Poster Authors

Jeffrey Boon

PhD, RN, AGACNP-BC

The Ohio State University

Lead Author

E-mail

Stephen P. Bruehl

PhD

Vanderbilt University Medical Center

Lead Author

E-mail

Mary S. Dietrich

PhD

Vanderbilt University

Lead Author

E-mail

Ronald L. Cowan

MD

The University of Tennessee Health Science Center

Lead Author

E-mail

Michelle Failla

The Ohio State University

Lead Author

E-mail

Karen O. Moss

PhD

The Ohio State University College of Nursing

Lead Author

E-mail

Aaron McDaniel

The Ohio State University

Lead Author

E-mail

Asvena Siva

BS

The Ohio State University College of Nursing

Lead Author

E-mail

Ashleigh Fletcher

BS

The Ohio State University College of Nursing

Lead Author

E-mail

Todd B. Monroe

PhD

The Ohio State University College of Nursing

Lead Author

E-mail

Topics

  • Pain in Special Populations: Elderly