Pupillary responses to thermal pain stimulation in healthy volunteers!
Lauren A. Banker, Troy C. Dildine, Lauren Y. Atlas, Ph. D!
Affective Neuroscience and Pain Lab, National Center for Complementary and Integrative Health!
Introduction!
!
Results!
!
!
!
•  ! Pain = “an unpleasant sensory and emotional experience
! associated with actual or potential tissue damage, or described in
! terms of such damage” 1. !
! !
•  ! The autonomic nervous system (ANS) is activated in response
2
! to pain . The parasympathetic nervous system (PNS) and the
! sympathetic nervous system (SNS) comprise the ANS, and
2. physiologically
respond
to
pain
in
various
ways
!
!
Pupil dilation increases as temperature increases; Pupil dilation increases as pain rating increases;
!
Pupil dilation revealed no sex or duration differences when correlated with VAS pain rating
Summary
!
! •  The magnitude of pupil dilation is related to
! increases in temperature and increases in
! pain ratings!
!
!
!
Temperature Effects on PD
!
!
Pain Ratings and PD
Mean centered temperature on average PD (n = 13)
!
Conclusions!
Mean centered VAS pain rating on average PD
(n = 14)
!
! Fig. 1 Schematic of pupil response to pain!
!
•  No sex or heat duration group differences in
!
VAS pain on average PD; no sex differences
!
in pain ratings or temperatures given!
!
!
!
!
!
Increased pupil
dilation (PD) has
correlated with
increases in: !
•  Pain Intensity 3,4,5,7,8!
•  Temperature 6!
•  Pain ratings 5,6!
•  Length of painful
SNS stimulus 6!
Radial muscles ! !
contract!
!
Pupil ! Circular muscles !
contract!
!
! Implications
!
!
!
!
!
! Questions
!
!
!
!
!
!
!
!
!
--Do increases in temperature elicit increases in pupil dilation?!
! --Do increases in pain ratings reflect increases in pupil dilation?!
! --Does duration of thermal pain stimulation affect pupil dilation?!
! --Do pupil dilation responses differ by sex?!
Overall
10.0
8.0
Rating
6.0
1.5!
4.0
2.0
0.0
35
45
Temp
Time (s)!
Visual Analog Pain Scale (VAS Pain)
0 = No sensation!
1 = Warmth, No
Pain!
2 = Slight Pain!
5 = Moderate Pain!
8 = Most Pain
Tolerated!
Above 8 = Worst
Pain!
!
!
!
!
!
!
!
! Further research
•  PD and other forms of eye-data (saccades, !
interest areas)!
!
Mean centered VAS pain rating on average
PD across sex (Females: n = 8; Males: n = 6)
Group!
AVG!
Individuals!
Mean temperature applied for pain stimulus
(Females: n = 8; Males: n = 5)
Male!
Female!
No
differences in
VAS pain
rating and
average PD
between men
and women !
Group!
AVG!
Acknowledgments!
Male!
Female!
50 49 48 No
differences
in
temperatures
given
between
men and
women!
47 46 45 44 43 42 41 References!
!
!
t = 0.95, p = 0.36, sd = 1.87 !
Pain Duration Differences in PD
!
Mean centered VAS on average PD across length
of trial (Long – Short) (Long: n = 11, Short: n = 3)
Individuals!
Male!
Female!
Men did not
report
different levels
of pain (VAS)
compared to
women!
Temperature (Mean Centered)!
Intercept: ß = 0.20 , t = -0.88, p = 0.40 !
Group!
AVG!
!
!
Short!
Long!
Individuals!
Na$onal Ins$tutes of Health Summer Internship Program Affec$ve Neuroscience and Pain Lab ! !
1. ! International Association for the Study of Pain (2015)!
2. Andreassi, J. L. (2007). Pupillary response and !
behavior In J. L. Andreassi (Eds.), Psychophysiology !
(289-307). New York, NY: Taylor & Francis Group. !
!
3. Bertrand et al. (2013). Pupillometry: !
!
The influence of gender and anxiety on the pain !
!
response. Pain Physician 16(3), E257-E266.!
4.! Chapman et al. (1999). Phasic pupil dilation !
response to noxious stimulation in normal volunteers: !
! Relationhip to brain evoked potentials and pain report. !
Psychophysiology 36(1), 44-52.!
5. Ellermeier, W., & Westphal, W. (1995). Gender !
differences in pain ratings and pupil reactions to !
painful pressure stimuli. Pain 61(3), 436-439.!
6. Geuter et al. (2014). Parametric trial-by-trial prediction !
of pain by easily available !
physiological measures. Pain 155(5), 994-1001.!
7. Hölfe et al., (2008). You can see pain in the eye: !
Pupillometry as an index of pain intensity under !
different luminance conditions. International Journal of !
Physiology 70(3), 71-175. !
8. Oka et al. (2007). Pupil dilation response to noxious !
stimulation: Effect of varying nitrous oxide !
concentration. Clinical Neurophysiology 118(9), !
2016-2024. !
Female Average Temperature Male Average Temperature Sex!
Mean centered temperature on
VAS Pain Rating across sex
(Females: n = 8; Males: n = 5)
Fig. 2a VAS Pain Rating Scale!
Pupil Size (A.U.)
!
•  PD and Expectancy effects!
Sex Differences in PD
Intercept: ß = -24.04 , t = -0.56, p =0.59 !
Time (ms)
!
Intercept: ß = 867.96, t = 2.87, p < .05 !
As VAS pain rating increases by 1 unit,
average pupil size increases by 11.16 A.U. !
VAS Pain Rating (Mean Centered)!
Fig. 2d Process of!
removing blinks!
and artifacts!
measures during thermal pain stimulation!
VAS Pain Rating (Mean Centered)!
7 (Mean Centered, °C)!
Temperature
!
40 Interpolated Pupil Data with Blink And Artifact Removal
! •  PD in relation to other physiological !
!
VAS Pain Rating!
Temp(° C )!
12.0
1.5!
!
!
Average Pupil Dilation (A. U.)!
Fig. 2b Medoc Heat ! Fig. 2c Time-course ! Fig. 2d Graph of pain !
Thermode!
of Pain !
rating reliability x temp!
5 / 7!
!
Intercept: ß = 861.29, t = 3.7, p < .01, !
As temperature increases by 1° Celsius!
pupil dilation increases by 12.86 A.U. !
Rating Reliability
•  Our findings suggest that pupil dilation is a
promising method for measuring pain,
especially when subjective reports cannot
be measured!
!
•  Physiological measures are an attractive
alternative to imaging techniques for
measuring pain!
!
Methods!
Pain Stimulus
!
Average Pupil Dilation (A. U.)!
PNS !
Individuals!
!
Mean temperature (° C ) !
!
Group AVG!
Average Pupil Dilation (A. U.)!
!
Individuals!
Average Pupil Dilation (A. U.)!
!
!
Group AVG!
!
!
No differences
in VAS pain
rating and
average PD for
long versus
short duration
of heat
stimulus !
!
!
!
!
!
!
!
!
!
!
VAS Pain Rating (Mean Centered)!
Intercept: ß = -80.15, t = -0.01, p = .99 !
!
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