Endocrinological Bases of Individual Differences of Pain Expression

FR272~Endocrinological Investigation of Exercise Effects by Using Different Instruction Styles~
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Ay Nakae , Wei-Chuan Chang , Chie Kishimoto , Hani M. Bu-Omer , Hidenobu SumiokaaPresence Media Research Group, Hiroshi Ishiguro Laboratories, Deep Interaction Laboratory Group, Advanced Telecommunications Research Institute International, JapanbGlobal Center for Medical Engineering and Informatics, Osaka University, Japan

Results & Discussion
CortisolFigure 1. Relationship between the brain and the entire body, with a particular focus
on the role of hormones and the autonomic nervous system.

Pre 15min Just 1h
after after

Type 1

Type 2

Duration Time•
Peak Temp. = 10 s•
Other Temp. = 15 s

Experimental heat stimulation

Agreeableness:
High Agreeableness: Individuals are compassionate, cooperative, and empathetic. They tend to be trusting and helpful
towards others.
: Individuals may be more competitive, critical, and less concerned with others' feelings.

PATHWAY (Medoc Ltd.)

Low AgreeablenessHigh Neuroticism

OriginFunction

Growth Hormone(GH)

1h after
1 hourA

CortisolGroup Exercise

LactateFigure 2. Study Design

Conclusions

DHEA-SThis study highlights the intricate link between personality traits, hormonal
responses, and pain perception, and suggests that tailored training interventions
could enhance pain tolerance and overall well-being.

Training Effectiveness and Motivation
Individual differences in training effectiveness and motivation may be related to the
HPA-axis function. Repeated intensive interventions, such as personal training, could
potentially align the hormone secretion patterns of individuals with poor training
efficiency with those of more autonomously trained individuals.

Clinical Imprecation
Individuals exhibit unique pain sensitivity and expression patterns. This study
demonstrates that these variations originate in the brain, providing insights forhealthcare professionals to better understand and manage patients' pain experiencesin clinical settings.

Adrenal glands

Stress response, increases blood sugar
levels, enhances glucose use in brain

Stress resilience?
Predictive marker of physical training
strength

Produced during
anaerobic respirationin muscles

Energy source for muscles, involved inmetabolic processes

Adrenal glands

Precursor to sex hormones(testosterone, estrogen), role in puberty
and secondary sexual characteristics

Predictive marker of physical training
strength

Affects mood, energy levels, andimmune function

Active Ghrelin

StomachStimulates appetite, increases foodintake, promotes fat storage

LeptinRegulates energy balance by inhibiting
hunger, signals satiety to the brain,
regulates food intake and body weightPre

Just 1hafter after

Pre

-2000

Just 1hafter after

Type 2

1.

Bar-Shalita, T., & Cermak, S. A. (2020). Multi-sensory Responsiveness and Personality Traits Predict Daily Pain Sensitivity. Frontiers in
Integrative Neuroscience, 13,77. https://doi.org/10.3389/fnint.2019.00077

2.

Vassend, O., Røysamb, E., & Nielsen, C. S. (2013). Five-factor personality traits and pain sensitivity: a twin study. Pain, 154(5), 722–728.
https://doi.org/10.1016/j.pain.2013.01.010
Almagor, M., Tellegen, A., & Waller, N. G. (1995). The Big Seven model: A cross-cultural replication and further exploration of the basic
dimensions of natural language trait descriptors. Journal of Personality and Social Psychology, 69(2), 300–307. https://doi.org/10.1037/00223514.69.2.300
Grouper, H., Eisenberg, E., & Pud, D. (2021). More insight on the role of personality traits and sensitivity to experimental pain. Journal ofPain Research, 14,837–1844.https://doi.org/10.2147/JPR.S309729

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Type 1

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2000

B

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*

1.5
1

***

1500

1000

500

0.5
0

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after afterPre

Just 1hafter after

Personal Training

Group Training0

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after afterPre

Personal Training

Group Training

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Just 1hafter afterPre

Type 2Just 1hafter afterPre

Type 1

Just 1hafter after

Type 2Just 1hafter after

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15

***

In the KAATSU condition, compared to pre-training, serum leptin
levels significantly decreased 15 min after and just after the training(p=0.0137;0.0266, respectively). In the circuit condition, comparedto just after the training, the serum leptin level significantly
increased 1 hour after the training (p=0.0021). There was nochanges in different type.

10

5

0

Pre 15min Just 1h
after afterPre

Just 1hafter after

Personal Training

Group Training

Figure 8. Different secretion changes between (personal training (KAATSU training) vs. Group training (Circuit training) of (A) leptin and (B) Active Ghrelin

B

*

3

Expression of Pain & Big5 Scores

2.5

A

2

1
0.5

Pre 15min Just 1h
after afterPre 15min Just 1h
after after

C

Type 2B

Type 2

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Type 2

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100
80

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40

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20

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Type 1

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120

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3

Type 1

140

1.5

2.5

References***

Leptin & Active Chrelin

2

Known as the "hunger hormone, as asecondary effect of training

A secondary effect of training

***

**

6000

1000

Type 1
Adipose (fat) cells,
small intestine

*

5

2.5

0

Novelty of the Study
To the best of our knowledge, this study is the first to investigate the relationshipbetween personality traits, hormonal responses to training exercises, and individual
differences in pain expression.
Key Findings
The study results suggest a causal relationship between personality traits,
particularly neuroticism, and cortisol secretion via the HPA axis after training
exercises. This finding indicates an association between personality traits and pain
perception.

Promotes growth of bones and tissues,
cell repair, metabolism regulation

8000

3000

*
3

Focusing Points

Pituitary gland

7000
**

DHEA-SDHEA-S [pg/ml]

Just after
45min exercise******* ****

8000

In the KAATSU condition, compared to pre-training, serum lactate levels
significantly increased in 15 min and just after the training (15 min p<0.0001;
just after p<0.0001). Compared to 15 min after starting the experiment, theserum lactate level significantly decreased 1 hour after the training(p=0.0005). Compared to just after the training, the serum lactate levelsignificantly decreased 1 hour after the training (p=0.0001). In the circuit
condition, compared to baseline, the serum lactate level significantly
increased just after and 1 hour after the training (p<0.0001 & p=0.0186,
respectively). Compared to just after the training, the serum lactate levelsignificantly decreased 1 hour after the training (p<0.0001). Lactate canreflect the training strength but both type looked almost equal lactate
secretion..

DHEA-S [pg/ml]

Pre

Type 2In the KAATSU condition, compared to pre-training, serum GH levels
significantly increased just after the training (p=0.0019). Compared to justafter the training, the serum GH level significantly decreased 1 hour after
the training (p=0.0010). In the circuit condition, compared to the baseline,
serum GH level significantly increased just after the training (p=0.0044).
Compared to the just after the training, serum GH level significantly
decreased 1 hour after the training (p=0.0022)
Especially in the KAATSU condition, there was no changes in 15min in
type2, however, just after the training there was significant change also in
type2. This result may suggest that cortisol hyper secreter(type1) cancontrol their training anytime but personal training can influence better to thehypo-secreter(type 2)

15min after
Pain perception?
Reflect effectivity on physical training

Type 1After cluster analysis using the cortisol data(B), seven participants were included in the high cortisol group (Type1)
and seven in the low cortisol group (Type2). In the KAATSU condition for Type1 group, compared to pre-training,serum cortisol levels significantly increased in all timings (15min p<0.0001; just after p=0.0040; 1 hour after
p=0.0005). Compared to 15 min after starting the experiment, the serum cortisol level significantly increased justafter training (p=0.0210). In the KAATSU condition of Type2 group, compared to pre-training, serum cortisol levels
significantly increased just after the training (p=0.0220). Compared to just after the training, the serum cortisol levelsignificantly decreased (p=0.0449) in 1 hour after the end of the training. In the circuit condition for Type1,
compared to the baseline, the serum cortisol level significantly increased just after and 1 hour after the training(p=0.0007; p=0.0053). Compared to just after the training, the serum cortisol level significantly decreased 1 hour
after the training (p=0.0035).In the circuit condition in Type2, compared to the baseline, the serum cortisol levelsignificantly increased just after and 1 hour after the training (p=0.0419; p=0.0173). Compared to just after the
training, the serum cortisol level significantly decreased 1 hour after the training (p=0.0018).

Table 1: Hormones and their functions for the purposes of this study.
HormonePre 15min Just 1h
after after

Figure 6. Different lactate changes between (A) personal training(KAATSU training) vs. Group training (Circuit training), (B) different
secretion pattern of the two types in personal training, and (C) different
secretion pattern of the two types in group training: Individuals are more prone to experiencing negative emotions such as anxiety, anger, or depression.
They may be more sensitive to stress and emotionally reactive.
: Individuals are more emotionally stable, calm, and less likely to experience negative emotions.

Low Neuroticism

Personal Training

10

Pre 15min Just 1h
after after

Figure 5. Different GH changes between (A) personal training (KAATSU
training) vs. Group training (Circuit training), (B) different secretion
pattern of the two types in personal training, and (C) different secretion
pattern of the two types in group training

Neuroticism:

B. The Timing of the Blood Collection for the Exercise Experiment

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13000

Continuous

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2

C

1.5
1
0.5
0

Pre

Just 1hafter after

Type 1Pre

Just 1hafter after

Type 2

Schuch, F. B., & de Almeida Fleck, M. P. (2013). Is Exercise an Efficacious Treatment for Depression? A Comment upon Recent Negative
Findings. Frontiers in Psychiatry, 4, 20. https://doi.org/10.3389/fpsyt.
Bouchard, C., & Rankinen, T. (2001). Individual differences in response to regular physical activity. Medicine and Science in Sports andExercise, 33(6 Suppl), S446-51; discussion S452. https://doi.org/10.1097/00005768-200106001-00013
Box, A. G., Feito, Y., Brown, C., & Petruzzello, S. J. (2019). Individual differences influence exercise behavior: how personality, motivation,and behavioral regulation vary among exercise mode preferences. Heliyon, 5(4), e01459. https://doi.org/10.1016/j.heliyon.2019.e01459

Figure 7. Different DHEA-S changes between (A) personal training(KAATSU training) vs. Group training (Circuit training), (B) different
secretion pattern of the two types in personal training, and (C)different secretion pattern of the two types in group training

Naugle, K. M., Fillingim, R. B., & Riley, J. L. (2012). A meta-analytic review of the hypoalgesic effects of exercise. The Journal of Pain,
13(12), 1139–1150. https://doi.org/10.1016/j.jpain.2012.09.006
Kami, K., Tajima, F., & Senba, E. (2017). Exercise-induced hypoalgesia: potential mechanisms in animal models of neuropathic pain.
Anatomical Science International, 92(1), 79–90. https://doi.org/10.1007/s12565-016-0360-z
Almagor, M., Tellegen, A., & Waller, N. G. (1995). The Big Seven model: A cross-cultural replication and further exploration of the basic
dimensions of natural language trait descriptors. Journal of Personality and Social Psychology, 69(2), 300–307. https://doi.org/10.1037/00223514.69.2.300

In the KAATSU condition, compared to pre-training, the serum DHEA-S
levels significantly increased in 15 min and 1 hour after the training (15 min
p=0.0195; just after p=0.0351). In the circuit condition, compared to thebaseline, the serum DHEA-S level significantly increased just after and 1
hour after the training (p=0.0012; p=0.0461). Compared to just after the
training, the serum DHEA-S level significantly decreased 1 hour after the
training (p=0.0203).

Neuroticism Sub-trait Score

Temperature•
Peak Temp. = 49 ℃•
Baseline= 36 ℃

40

2000

Conscientiousness: Individuals are outgoing, energetic, sociable, and enjoy being around people.
They are often enthusiastic and action-oriented.
Low Extraversion (Introversion) : Individuals are more reserved, quiet, and prefer solitary activities or small groups over large social
gatherings.

3000

Type 1

30
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Type 2
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Type 130Type 2

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Self
Discipline

High Extraversion

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4000

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Big5 Score

Low Conscientiousness

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C

Neuropathic: Individuals are organized, dependable, disciplined, and have a strong sense of duty.
They tend to be goal-oriented and plan ahead.
: Individuals may be more spontaneous, less reliable, and prone to procrastination.

Extraversion:

42

Type 2Angry/
Hostility

High Conscientiousness

VAS

Type 1

Intermittent

Conscientiousness:

[℃]
50

44

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after after

18000

Anxiety

Low Openness*

SF-MPQ-2 Score: Individuals are imaginative, curious, open to new experiences, and have a broad range of interests.
They tend to be creative and open to trying new things.
: Individuals are more conventional, prefer routine and familiarity, and may be resistant to change.

**
***

6000

*

Leptin [pg/ml]

High Openness

SFMPQ2*Just 1hafter after

Figure 4. Different cortisol changes between (A) personal training (KAATSU training) vs. Group training(Circuit training), (B) how to divide into two groups based on the cluster analysis, (C) different secretion
pattern of the two types in personal training, and (D) different secretion pattern of the two types in grouptraining

DHEA-S [pg/ml]

Extraversion

Figure 3. Five factor Model48

Pre 15min Just 1h
after after***

Type 1Openness to Experience:

Detail explanation is Shown in Fig 3

C

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AgreeablenessA. The NEO-PIR Answering and the Hear Stimulation Experiment
Experimental
Heat Pain
Stimulation

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10000

GH [pg/ml]

C
Personality

Statistical analyses were conducted using JMP 17.0 with a corresponding one-tailed test and a significance level of 5%.

36

Pre 15min Just 1h
after after

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Cortisol [μg/ml]

N

Participants’ blood samples were collected at three time points: just before training, immediately after training, and one hour
after training. In the KAATSU condition, additional samples were taken 15 minutes after starting the KAATSU training. Serumlevels of cortisol, dehydroepiandrosterone-sulfate (DHEA-S), growth hormone (GH), and leptin were measured using enzyme
immunoassays. Detection limits for cortisol, DHEA-S, GH, and leptin were 45.5 pg/mL, 0.044 ug/mL, 2.10 pg/mL, and 2.13
pg/mL, respectively, with intra- and inter-assay variation coefficients under 10% (except leptin, under 10.2%). L-lactate levels
were measured using a bioluminescent assay with a detection limit of 200 uM. Active ghrelin levels in acidified plasma were
measured by ELISA, with a detection limit of 160 fmol/mL; variation coefficients were not provided by the manufacturer.

NEO-PIR*Group Training

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7000

*

25

Fourteen healthy participants completed the Big 5 NEO-PI-R, received experimental thermal stimuli, and answered SFMPQ-2.
Five hormones (GH, Cortisol, DHEA-S, Active Ghrelin, and Leptin) and lactate were measured in serum before, during, andafter exercising for 45-minute group and individually supervised exercise tasks; KAATSU training was chosen as a personaltraining task whereas circuit training was chosen as a group training.

Consent Explanation
Confirmation of subject
background

15000

Personal Training
8000

*

*

Pre

1000

****

The study protocol was approved by the Ethics Review Committee of the Graduate School of Frontier Biosciences, Osaka
University (FBS30-11) in accordance with the tenets of the Declaration of Helsinki. Written informed consent was obtained fromeach participant before their enrollment. The study design was shown in Figure 2.

B

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Conscientiousness

Group Training

Pre 15min Just 1h
after after

Agreeableness

Neuroticism

Personal Training0

Just 1hafter after

5000

Openness

Methods

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O

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Hormonal Influence on Pain: Exercise influences pain perception through the endogenous opioid system. Dysfunction in
the GH/ghrelin axis is linked to hyperalgesia and common pain syndromes[10] (Figure 1).
# Aim of the Study: This study aims to clarify the relationship between personality traits, hormone secretion (focusing on
the HPA-axis and GH/ghrelin-axis), and individual differences in pain expression.

Pre

Achievement
Striving

Mechanisms of EIH: Potential mechanisms include the roles of inflammatory cytokines, neurotrophins, neurotransmitters,
endogenous opioids, and histone acetylation in different parts of the peripheral nervous system[8,9].

20

Pre 15min Just 1h
after after*******

2000

Openness

Pain Perception: Exercise often reduces pain sensitivity through a phenomenon called exercise-induced hypoalgesia (EIH),
which is well-documented in healthy populations. However, the response to exercise in chronic pain patients varies, with someexperiencing increased pain[5,6,7].

Autonomic nervous system

0

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25

3000

1000

2000

B

4000

Assertiveness

Endocrine system

6000
4000

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30

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5000

Extraversion# Why We Chose Exercise Experiments?

C***

Sub-trait Score

heart rate, blood pressure
respiratory rate, blood sugarmuscle energy
Immunosuppression

***

8000

Neuroticism

Anti-inflammatory effects
Immunosuppression
Blood Sugar

Group Training

10000

Vulnerability

Chondrocyte proliferation
Acceleration of protein synthesis
Lipolysis
Electrolyte reabsorption

Personal Training

12000

Impulsiveness

Adrenaline

Just 1hafter after******

Total

CortisolPre****** ******

6000

Self
Consciousness

Growth hormone

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after after***

Lactate [μM]

0

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14000

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7000

Lactate [μM]

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A

Lactate [μM]10Cortisol [μg/ml]# Pain Sensitivity and Personality Traits: There is a limited but suggestive empirical relationship between pain sensitivity
and personality traits, particularly neurotic tendencies. Studies have shown correlations between daily sensation
responsiveness and traits like neuroticism, openness, and extraversion. Specific personality facets such as impulsiveness andexcitement-seeking are associated with experimental cold pain intensity[1,2]. Tools like the five-factor inventory[3] and the pain
catastrophizing scale can help identify personality traits related to high pain sensitivity[4].

*15Adrenal cortex

Background & Aim of the study*

Lactate16000

GH [pg/ml]

Adrenal medulla

Anterior pituitary gland Spinal cord

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A

1
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6
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12
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Type 1

Cortisol [μg/ml]

Hypothalamus

B*** ******

20

Growth Hormone

Type 2A*

GH [pg/ml]***

Affective

The study investigates the relationship between hormone secretion patterns in
response to exercise and individual differences in pain expression and personality
traits. Fourteen subjects were given thermal stimuli and their personality traits wereassessed using the NEO Personality Inventory (NEO-PI-R). Blood samples weretaken to measure cortisol and growth hormone levels. Subjects were divided into twogroups based on cortisol secretion: hyper-secretors (Type1) and hypo-secretors(Type2). Hyper-secretors showed significantly lower neuroticism scores and pain
ratings compared to hypo-secretors. The findings suggest that cortisol
responsiveness to exercise may be linked to pain sensitivity and neuroticism,
indicating that personality traits could be related to hormone secretion patterns.

Active Ghrelin [fmol/ml]

Exercise-Induced Physical and Mental Stress

Depression

Abstract

Figure 9. Different expression of (A) pain (B) the scores of Big 5 each scale, (C) the scores of Big 5 Neuroticism subscales, and (D) the scores of other significant in two types
The participants from the Type2 group expressed pain significantly more in the continuous component (p<0.05).The neuroticism score was significantly higher in the Type2 group compared to the Type1
group (p<0.05). Then, we examined the sub-trait of neuroticism. Anxiety, depression, and vulnerability scores were significantly higher in the Type2 group (p< 0.05), as was the self-consciousness score(p<0.005).Only assertiveness subscale showed a significant difference with the higher score in Type1(p<0.05).
The people who express higher in experimental pain condition may have a sensitive personality derived from different types of secretion of hormones.

Acknowledgement: This work was supported by JST Moonshot R&D Grant Number JPMJMS2011 (investigation of hormonal effect), JST CREST Grant Number JPMJCR18A1 (investigation of psychological effect), AMED under Grant Number JP21lm0203145 (investigation of evaluation of circuit training), and JP21he0122016 (investigation of evaluation of KAATSU training), Japan.