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1
Measuring the Autonomic Response in a Functional
Imaging Study of Pain Li, Michelle S.M. Owen,
Daron. St. Lawrence, K. The University of
Western Ontario Lawson Health Research
Institute at St. Josephs Health Care, London,
Ontario.
Abstract
Discussion
Objectives

• Partial statistical analysis show that for
  some individuals heart rate will increase
  when a pain stimuli is felt (further analysis is
  required).
• When the body is faced with a pain stimuli and
  its opioid receptors are able to release its
  pain-relieving chemicals, there is no
  significant effect of time on heart rate
  (p0.4716).
• In situations where the opioid receptors are
  blocked with an antagonist drug, the body
  will feel the pain more intensely and with
  time, heart rate will increase (p0.0209).
• When stimulating the brain, an increase in
  cerebral blood flow
• will occur in the regions affected by the
  stimuli. This fact can be used to allow
  one to quantitatively determine exactly which
  areas become activated by using fMRI.

It is commonly thought that when one
feels some sort of pain sensation, his or her
autonomic nervous system will activate and
trigger the infamous flight or fight response.
Rehabilitation clinicians utilize this
correlation while complementing objective
measures of pain. Specifically, this study
researches the correlation of pain and its effect
on increasing heart rate. In this controlled
study, with 37 healthy male volunteers who had no
history of neurological diseases or pain, either
present or chronic, were separated into two
groups control (no drug) and pain (drug) groups,
composed of 18 and 19 volunteers respectively.
The subjects heart beats were measured every 5.5
milliseconds for a total of 25 minutes. For the
first 11 minutes of the study (preinfusion
period), we measured the heart rate to obtain a
baseline. The next 14 minutes of the study
(infusion period), an infusion of hypertonic
saline (HS, 5 NaCl) solution, was used to mimic
pain similar to the chronic pain sensation. We
also took fMRI scans to see which regions of the
brain were activated with pain. The pain group
had taken an opioid receptor antagonist,
Naloxone, to prevent the release of endogenous
pain relieving chemicals. The hypertonic saline
solution was infused intramuscularly,at an
initial rate of 200 µL/min, with increments of
100 µL/min, to a maximum rate of 500 µL/min. The
results of this study show there is no effect on
heart with time for the control study (p
0.4716) and an effect with the pain group (p
0.0209). Further analysis is required to
determine if this is true for individual cases.

• To determine whether there was a significant
  autonomic response to pain during a neuroimaging
  study.

Methods
Data Analysis

• The study was completed at the Lawson Health
  Research Institute, approved by the Health
  Sciences Research Ethics Board of the
  University of Western Ontario.
• Study consisted of 37 healthy male subjects,
  with no history of neurological disorders,
  present or chronic pain.
• The subjects were split into two groups, a
  control group (just HS infusion) and a
  pain group (HS infusion with Naloxone,
  opioid receptor antagonist).
• HS solution was used as the pain stimulus
  because HS models the pain sensation very
  similar to chronic pain.
• During the study, fMRI scans were taken of
  the subjects brain to see the brain
  regions associated with tonic and chronic pain.
• Heart rate data was collected for 25 minutes
  the first 11 minutes were preinfusion to
  obtain a baseline, followed by 14 minutes
  of infusion with a hypertonic saline (HS, 5
  NaCl) solution at a rate of 200 µL/min,
  increasing to a maximum of 500 µL/min at
  increments of 100 µL/min.

• A program in MATLAB had to be written to
  count the number of heart beats which
  occurred in a desired amount of time.
• Since resting heart rate differs from
  individual to individual, the heart rate
  data had to be normalized to baseline.
• Statistical tests using GraphPad InStat were
  needed to determine if there is an effect
  on heart rate due to time (repeated
  measures ANOVA).
• To analyze if there is a correlation between
  heart rate and pain rating, a bivariate
  correlation test had to be done.

Conclusion

• Using fMRI, one can visually see the
  activated areas of the brain upon
  stimulation.
• In this study, we used a pain stimulus and
  saw that the regions activated were the
  insula and anterior cingulate cortex (ACC),
  which corresponded to research conducted by other
  research groups.
• After infusion, we observed no significant
  effect of time on heart rate for the
  control group (p0.4716), whereas we observed
  a significant effect in the pain group
  (p0.0209).
• Some individuals show there is a correlation
  between pain ratings and heart rate.

Introduction

• Neuroimaging has made it possible to
  determine which brain regions are
  associated with various cognitive and sensory
  tasks.
• Our group is focused on mapping out the
  brain regions involved with pain
  perception, particularly tonic and chronic
  pain conditions.
• There are several regions activated during
  pain stimulation. The main 2 regions are
  the insula and anterior cingulate cortex
  (ACC).

Results

• Within each group, some individuals displayed
  a correlation between heart rate and pain
  (but further statistical analysis is
  required).
• fMRI scans showed that with pain, the insula
  and ACC regions were the primary regions
  which were associated with pain
  (increased CBF).

• Both groups showed an increase in pain
  ratings around the time when infusion of HS
  solution began.
• For the control group, during the infusion
  period, there was no significant effect of
  time on heart rate after infusion began
  (p0.4716 repeated measures ANOVA).
• For the pain group, there was a statistically
  significant effect of time on heart rate
  after infusion began (p0.0209 repeated
  measures ANOVA).

Future Research

• Further statistical analysis is required to
  determine potential correlations between
  heart rate and pain rating for individual
  subjects.
• Our group will continue mapping out the brain
  regions involved with pain perception,
  using medical imaging techniques.

Acknowledgements

• Special thanks to Daron Owen, PhD candidate
  Dr. Keith St. Lawrence for all their help
  and knowledge on this project.
• The Medical Biophysics department at the
  University of Western Ontario all of the
  individuals involved in Medical Biophysics
  3302E to allow their students this wonderful
  opportunity.

References
(1) Stephenson, J. Pain and the Brain. JAMA.
2004, 291, (11), 1313. (2) Apkarian, A.V.
Bushnell, M.C. Treede, R.D. Zubieta, J.K..
Human brain mechanisms of pain perception and
regulation in health and disease. European
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L.A. Bandler, R. Gandevia, S.C. Macefield,
V.G.. Distinct Forebrain Activity Patterns During
Deep Versus Superficial Pain. Pain. 2006, 120,
286-296. Porro, C.A. Cettolo, V. Francescato,
M.P. Baraldi, P.. Functional Activity Mapping of
the Mesial Hemispheric Wall During Antipation of
Pain. Neuroimage. 2003, 19, 1738-1747. Tousignant
-Laflamme, Y. Rainville, P. Marchand, S..
Establishing a link between heart rate and pain
in health subjects A gender effect. Journal of
Pain. 2005, 6, (6), 341-347.
Figure 4a The average number of heart beats per
minute
Figure 4b The normalized heart rate per minute
Figure 4c The average
pain rating over time
Figure 2 The insula activated due to
Figure 3 The different regions of the empathy
(1) .
brain involved in pain perception (2).
Figure 5a The relationship between heart rate
and pain ratings for the control group
Figure
5b The relationship between heart rate and pain
ratings for the pain group