European Journal of Pain 8 (2004) 31–38

www.EuropeanJournalPain.com

The tridimensional personality theory and pain: harm avoidanceand reward dependence traits correlate with pain perception

in healthy volunteers

Dorit Pud a,b,c,*, Elon Eisenberg a,b,d, Elliot Sprecher b,d, Zeev Rogowski b,d,David Yarnitsky b,e,d

a Pain Relief Unit, Rambam Medical Center, Haifa, Israelb Haifa Pain Research Group, Israel

c Faculty of Social Welfare and Health Studies, University of Haifa, Haifa 31905, Israeld The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Israel

e Department of Neurology, Rambam Medical Center, Israel

Received 2 September 2002; accepted 26 May 2003

Abstract

The aim of the present study was to examine the possible role of personality traits in determining the variability of pain per-

ception among individuals. More specifically, it was intended to test whether or not the three personality dimensions suggested by

Cloninger in 1987 – mainly harm avoidance (HA), but also reward dependence (RD), and novelty seeking (NS), can predict in-

terpersonal differences in responsiveness to experimental pain. Seventy healthy volunteers participated in the study. Their per-

sonality traits were evaluated through Cloninger�s tridimensional personality questionnaire (TPQ). Pain threshold (latency to pain

onset), pain magnitude (VAS), and pain tolerance (time to withdrawal) were measured by using the cold pressor test. Bonferroni-

adjusted correlations were found between HA and the pain parameters as follows: a negative correlation between HA and threshold

(q ¼ �0:297, Padj ¼ 0:039); no significant correlation between HA and tolerance (q ¼ �0:219, Padj ¼ 0:207); and a trend for a

positive correlation between HA and VAS (q ¼ 0:266, Padj ¼ 0:081). Possible correlations between pain perception and the various

possible combinations of high and low scoring for each of the three traits were also investigated. Correlations were found only for

the combinations of high/low HA and high/low RD. The low HA/low RD combination demonstrated the lowest responsiveness to

pain (VAS 65.2� 21.4; tolerance 107.6� 71.8 s), whereas the high HA/low RD combination was correlated with the highest re-

sponsiveness (VAS 83.3� 10.8; tolerance 30.8� 28.4 s). The results indicate that HA personality trait correlates best with pain

responsiveness. As such, a high HA are likely to predict a heightened pain response. RD may modify this pattern. The possible

relevant behavioral and neuro-chemical mechanisms are discussed.

� 2003 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All

rights reserved.

Keywords: Cold pressor test; Pain magnitude; Pain threshold; Pain tolerance; Personality traits; Tridimensional personality theory

1. Introduction

There are large individual differences in the percep-tion of clinical and experimental pain, in the propensity

to develop painful syndromes, and in the response to

pain-relieving treatments. Experimental pain studies

show a wide range of stimulus–response relations

* Corresponding author. Tel.: +972-4-8288013; fax: +972-4-8288017.

E-mail address: doritpud@research.haifa.ac.il (D. Pud).

1090-3801/$30 � 2003 European Federation of Chapters of the International

reserved.

doi:10.1016/S1090-3801(03)00065-X

between the intensity of the noxious stimulus and the

reported magnitude of pain perception (Mogil, 1999a).

Furthermore, considerable interpersonal variability inpain thresholds has been demonstrated for pressure pain

(Brennum et al., 1989; Isselee et al., 1997), cold pressor

tolerance (Chen et al., 1989), and heat pain (Kleinbohl

et al., 1999; Yarnitsky et al., 1995, 1996).

Much effort has been invested over the years in an

attempt to identify factors predicting pain perception.

Although the results have not always been consistent,

Association for the Study of Pain. Published by Elsevier Ltd. All rights

32 D. Pud et al. / European Journal of Pain 8 (2004) 31–38

several factors have been found to correlate with dif-ferent pain parameters. First, most clinical trials have

found gender-dependent differences in pain perception,

with women reporting more intense, prolonged and

frequent pain than men (Fillingim and Maixner, 1995;

Keefe et al., 2000; Riley et al., 1998; Unruh, 1996).

Experimental pain studies, on the other hand, have been

less consistent regarding gender differences in pain per-

ception, depending partially on the pain modality used(Fillingim et al., 1997; Lautenbacher and Strain, 1991;

Lautenbacher and Rollman, 1993). Second, high anxiety

levels have been found to correlate with post-operative

pain magnitude (Thomas et al., 1998), labor pain

(Green, 1993), and experimental pain induced by elec-

trical stimulation (Janssen and Arntz, 1999). Third,

cultural background has been shown to influence the

response to experimental and acute pain (see the reviewby Williams, 1999). Fourth, pain perception has been

shown to be associated with autonomic activity, as re-

flected in the association between increased arterial

blood pressure and decreased perception of pain (al�Absi

et al., 1999; Ditto et al., 1993; Ghione et al., 1988; Zamir

and Shuber, 1980). Finally, recent animal studies have

demonstrated the influence of genetic factors on pain

perception (Mogil et al., 1999b; Mogil, 1999c).An area of great interest in this context is the role of

personality traits in pain perception. Personality traits

are defined as ‘‘deeply ingrained patterns of behaviors,

which include the way one relates to, perceives, and

thinks about the environment and oneself that are ex-

hibited in a wide range of social and personal contexts’’

(American Psychiatric Association, 1994). Since pain is

widely accepted to be a bio-psychosocial process (Turk,1996), it is very likely to be influenced by personality.

Over the years, researchers have investigated the con-

tribution of personality to pain perception, both

through experimentally induced pain models as well as

in various clinical settings. The different parameters

measured include pain threshold, pain magnitude, tol-

erance, and pain behavior. Still, findings are inconsistent

and the relationship between personality and the variouspain parameters remains unclear (Phillips and Gatchel,

2000).

A unique personality theory that appears to make a

great contribution to the understanding of psychiatric

disorders is Cloninger�s tridimensional personality the-

ory (Cloninger, 1986, 1987; Hansenne et al., 1998; Nel-

son and Cloninger, 1997; Russo et al., 1994). This theory

is derived from the unified bio-social model of person-ality and is based on the hypothesis that neuro-chemical

transmitters determine stimulus–response characteris-

tics. Accordingly, three sets of behavioral manifestations

and their corresponding neuro-transmitters are hy-

pothesized: (1) Novelty seeking (NS), described as a

tendency to respond with intense excitement to novel

stimuli, leading to pursuit of rewards and escape from

punishment. This trait is associated with dopamine. (2)Harm avoidance (HA), defined as a tendency to respond

intensely to previously established signals of aversive

stimuli and to learn to passively avoid punishment,

novelty and frustrating non-reward. This trait is asso-

ciated with serotonin. (3) Reward dependence (RD),

characterized as a tendency to respond intensely to sig-

nals of reward and to maintain behavior previously as-

sociated with reward or with relief of punishment. Thistrait is associated with noradrenaline.

This theory is assumed to have relevance for pain

perception given that serotonin and noradrenaline are

the major neurotransmitters in the inhibitory modula-

tion of pain through descending pathways (Fields and

Basbaum, 1999). Dopamine may also be involved in

pain processing, as suggested by the painful syndromes

described in Parkinsonian patients (Chudler and Dong,1995). Furthermore, behaviors along the lines delineated

by the Cloninger theory may correspond to pain-related

behavior. For example, avoidance of harm is probably

equivalent to avoidance of pain, so that high scores on

harm avoidance would likely produce relatively high

scoring of painful stimuli.

The aim of our study was to examine the possible role

of personality traits in explaining the variability of painperception among individuals. Specifically, we at-

tempted to identify the relationships between personal-

ity traits and the parameters of pain threshold, tolerance

and magnitude estimation. To the best of our knowl-

edge, this is the first attempt to implement Cloninger�stheory in the context of pain perception. Our working

hypothesis was that individuals with high HA scoring,

who are nearly always fearful and anticipating harm,pessimistic and inhibited by unfamiliar situations, would

probably express high pain response. We assumed that

the other two dimensions will not, by themselves, predict

pain perception; NS because of the unpredictability of

the individual response, and RD because of their heavy

inconsistency and dependence on circumstances.

2. Method

2.1. Subjects

Seventy healthy volunteers participated in the study

at Rambam Medical Center in Haifa, Israel. The study

included 38 male and 32 female subjects, with ages

ranging from 18 to 40 years (mean 24.3� 3.9, SD). Thevolunteers were recruited mostly from the student body

of the medical and nursing schools, and enrolled in the

study after meeting the following criteria: (1) freedom

from chronic pain of any type; (2) no use of any medi-

cation (except oral contraceptives); and (3) ability to

understand and follow the instructions of the study. All

subjects were paid for participating the study. A written

D. Pud et al. / European Journal of Pain 8 (2004) 31–38 33

informed consent was obtained from all subjects prior tobeginning the study. The study protocol was approved

by the hospital�s Ethics Committee and the National

Board of Health in Israel.

2.2. Instruments

2.2.1. Personality trait evaluation

The tridimensional personality questionnaire (TPQ)is a 100-item true/false self-report inventory (Cloninger,

1987). It has been translated into several languages and

used in a variety of studies. The questionnaire has been

translated into Hebrew, and this version�s reliability was

demonstrated by high Cronbach�s alpha (0.90 for NS,

0.89 for HA, and 0.85 for RD) (Gil, 2003). Nixon and

Parsons (1989) provided evidence for the construct va-

lidity of the questionnaire in a sample of 225 male andfemale college students. They analyzed scores for each

personality dimension with respect to gender, academic

major, college GPAs, and abstraction test scores. Their

results support Cloninger�s theoretical concept of three

essentially independent personality dimensions. This

instrument measures the three primary personality fac-

tors thought to be involved in the mediation of partic-

ular types of stimuli, with 34 questions relating to NS,another 34 questions to HA, and 30 questions to RD

(Cloninger et al., 1991). Two questions (No. 61 and 71)

were excluded from scoring because of non-specificity

(correlations with multiple factors) (Cloninger, 1987).

Test–retest correlations were found to be moderately

high (Cloninger et al., 1991). The total score for each

dimension was calculated.

2.2.2. Experimental cold tonic pain

The cold pressor test (CPT) apparatus (Heto CBN

8-30 Lab equipment, Allerod, Denmark) is a tempera-

ture-controlled water bath of 1.0 �C, with a maximum

temperature variance of �0.5 �C, that is continuously

stirred by a pump.

2.3. Study protocol

All subjects completed the Hebrew version of the

TPQ. As for the cold pressor test, following the standard

protocol (see e.g., Wolff, 1984), subjects were asked to

place their non-dominant hand in the CPT bath in a still

position with the fingers wide apart for as long as they

could. A cut-off time of 3 min was set for safety reasons.

This initial immersion was considered training or fa-miliarization, and the results were not used in the sta-

tistical analysis. Thirty minutes later, a second CPT

immersion was conducted in the same manner and re-

garded as the baseline measure.

Subjects were instructed to indicate the exact point in

time when the cold sensation began to hurt, and they

first felt pain. This was defined as the pain threshold.

The latency to intolerability (spontaneous hand re-moval) was defined as pain tolerance. Tolerance for

subjects that did not withdraw their hand for the entire

180 s was recorded as 180 s. Immediately after with-

drawing their hand, subjects were asked to mark on a

100 mm VAS ruler the maximal pain intensity they ex-

perienced during the cold stimulus. The VAS was de-

fined a priori to the subjects as a continuum with one

anchor at 0, representing �no pain at all�, and the otheranchor at 100, representing the �worst pain one can

imagine�. This mark was defined as the pain magnitude.

2.4. Statistical analysis

Statistical analysis employed ANOVA, linear regres-

sion and Spearman correlations (q indicates Spearman

correlation). Shapiro–Wilk tests were used to examinethe deviation of result distributions from normality.

Arcsine, log, or square root transformations (Zar, 1984)

were employed as needed to improve the normality of

result distributions and to enable the use of ANOVA.

Excel (Microsoft Corp., WA, USA), JMP, and SAS

(SAS Institute, NC, USA) were employed in the statis-

tical analyses. Results were considered significant at the

0.05 levels; if multiple tests were required, raw P valueswere Bonferroni-adjusted appropriately. All results are

given as means� SD.

3. Results

3.1. Personality traits

Analysis of the 70 TPQ questionnaires from the

present study showed a NS mean score of 16.4� 4.4; an

HA mean score of 9.6� 5.6; and a RD mean score of

19.2� 4.7.

3.2. Pain perception

The results demonstrate that exposure to the CPTproduced significant pain, as measured by the three

different variables of threshold, tolerance, and magni-

tude (see Table 1), without causing any harm to the

subjects. These results are in line with those reported in

previous studies (Cleeland et al., 1996; Eckhardt et al.,

1998; Fromm et al., 1997; Garcia de-Jalon et al., 1985;

Jones et al., 1988; Lovallo, 1975; Peckerman et al., 1994;

Poulsen et al., 1995). Results of the CPT are as follows.

3.2.1. Threshold

Mean threshold was 7.1� 4.5 s, ranging from 1 to 24 s

(see Fig. 1A). Since the distribution of threshold among

subjects was not normal, a log transformation was used

for normalization, as confirmed by the Shapiro–Wilk test

(P ¼ 0:279).

Table 1

Pain parameters in response to CPT (n ¼ 70)

Threshold (s) (THRE) Tolerance (s) (TOL) VAS (0–100)

Mean� SD 7.1� 4.5 54.8� 46.9 72.8� 15.8

Median 6 38 73

Range 1–24 6–180 20–100

34 D. Pud et al. / European Journal of Pain 8 (2004) 31–38

3.2.2. Tolerance

Mean tolerance was 54.8� 46.9 s, ranging from 6 to

180 s (see Fig. 1B). About two-thirds of the subjects

demonstrated high sensitivity to cold stimuli and could

tolerate the pain for no more than 60 s. The others were

found to be more tolerant to cold pain and could keep

their hands in the water for a longer time. This distri-

bution is similar to previously published data (Chenet al., 1989; Cleeland et al., 1996). The distribution of

this data was not normal, and no conventional trans-

formation technique was able to normalize it.

3.2.3. Pain magnitude

Mean VAS was 72.8� 15.8, ranging from 20 to 100

(see Fig. 1C). Since the distribution of pain magnitude

among subjects was not normal, the arcsine transfor-mation was successfully used for normalization, as

confirmed by the Shapiro–Wilk test (P ¼ 0:755).Spearman correlations, on untransformed data, for

non-parametric variables found a significant positive

correlation between threshold and tolerance (q ¼ 0:622,P < 0:0001) and negative correlations between VAS and

tolerance (q ¼ �0:218, P ¼ 0:038), as well as between

VAS and threshold (q ¼ �0:208, P ¼ 0:048).

Fig. 1. Threshold (A), tolerance (B), and magnitude (C) of pain in

response to CPT.

3.3. Relationship between personality traits and pain

perception

In order to avoid statistical problems with non-normal

distributions and outlying data, we performed three

Spearman correlations, relating the HA scores separately

to each of the three pain measures. Raw P values were

Bonferroni-adjusted by multiplication by 3. Correlations

were found between HA and the pain parameters as

follows: a negative correlation between HA and thresh-

old (q ¼ �0:297, P ¼ 0:013, Padj ¼ 0:039) (see Fig. 2A);no significant correlation between HA and tolerance

(q ¼ �0:219, P ¼ 0:069, Padj ¼ 0:207) (see Fig. 2B); and atrend for a positive correlation between HA and VAS

(q ¼ 0:266, P ¼ 0:027, Padj ¼ 0:081) (Fig. 2C).Thus, individuals with high HA scores demonstrated

enhanced sensitivity to painful stimuli, as expressed by a

low pain threshold and increased pain perception. In a

separate analysis, NS and RD failed to demonstratesignificant correlations with any of the pain parameters.

A further analysis using linear regression on trans-

formed data indicated that, when taken together, HA

and RD demonstrated a trend toward a correlation with

pain magnitude (P ¼ 0:084). The other combinations of

the personality traits (HA and NS; NS and RD) failed to

show correlations with any pain parameter.

Consequently, the subjects were then categorized into

two different groups for each trait, with the mean point

score delineated as the cut-off point. A mean rather than

median was used, in order to follow as closely as pos-

sible the original report by Cloninger (1987). Thus, sixdifferent subgroups (high score and low score for each

trait) were created. This was followed by a pairing of the

traits (e.g., HA and RD) so as to produce three 2� 2

cross-tabulations (e.g., high and low HA vs. high and

low RD). For the HA/RD interaction, we found that the

low HA/low RD group demonstrated the lowest pain

magnitude (VAS 65.2� 21.4), whereas high HA/low RD

showed the highest pain magnitude (VAS 83.3� 10.8).The other two groups (low HA/high RD and high HA/

Fig. 2. Scatter plots of correlations between threshold (A), tolerance

(B), and pain magnitude (C), and HA scores. The P value for each

Spearman correlation has been Bonferroni-adjusted for the three

comparisons.

D. Pud et al. / European Journal of Pain 8 (2004) 31–38 35

high RD) were in-between (VAS 73.6� 15.1 and

73.2� 14.3) (see Fig. 3). ANOVA on the transformed

data indicated that this difference was statistically sig-

nificant (P ¼ 0:026).The same pattern was found in regard to pain toler-

ance. The low HA/low RD group demonstrated the

longest tolerance (107.6� 71.8 s), whereas the high HA/

low RD group showed the shortest tolerance(30.8� 28.4 s). Here too, the other two groups were in-

between (54.4� 42.9) and (51.6� 46.4), with statistical

significance at the P ¼ 0:002 level. Likewise, regarding

pain threshold, the low HA/low RD group demon-

strated the longest threshold (7.3� 4.6 s), whereas the

high HA/low RD group showed the shortest threshold

(5.2� 3.2 s). The other two groups were in-between

(6.9� 4.1 and 7.0� 3.2 s). ANOVA indicated only atrend toward significance for this variable (P ¼ 0:083).

Analysis of HA vs. NS and of RD vs. NS, using thesame methodology, failed to show any significant results.

4. Discussion

The findings of the present study suggest that per-

sonality traits can play an important role in the under-

standing of the variability of pain perception amongindividuals in pain perception. More specifically, they

indicate that the personality traits described by Clon-

inger may predict responsiveness to cold-induced ex-

perimental pain. High HA level alone and – even more

so – a combination of high HA and low RD seems to be

the most important traits in the determination of

heightened cold pain perception.

Clinically, Cloninger�s model has been the basis for alarge number of studies on various psychiatric disorders,

such as depression, anxiety disorders, and suicidal be-

havior (Gil, 2003; Hansenne et al., 1998; Herran and

Vazquez, 1998; Nelson and Cloninger, 1997; Starcevic

et al., 1996). Hansenne et al. (1998) demonstrated higher

harm avoidance scores and lower novelty seeking scores

among depressed patients as compared to healthy con-

trols. Gil (2003) found that psychiatric patients charac-terized by high levels of both HA and NS are at greater

risk for suicide attempt. Menza et al. (1993) found low

scores for the novelty-seeking trait, which represents

dopaminergic activity, among Parkinson�s patients as

compared to a group of other orthopedic patients with

motor disturbances.

Possible relations between personality traits and pain

perception have been discussed by several earlier writers.A common theoretical perspective used to examine

personality was proposed by Eysenck (1960), who di-

vided personality into two main independent, uncorre-

lated factors: extroversion–introversion and neuroti

cism-stability. He defined extroverted people as more

outgoing, uninhibited and socially active, whereas in-

troverts were considered to be quieter, more introspec-

tive and reserved. In examining the relationship betweenpersonality and experimental heat pain, Lynn and Ey-

senck (1961) found higher tolerance among extroverted

subjects, whereas other researchers (Brown et al., 1973;

Martin and Inglis, 1965) using the cold pain model

failed to report a significant relationship.

As for clinical pain, Bond et al. (1976) found higher

pain magnitude among extroverted patients suffering

from back surgery pain, whereas Taenzer et al. (1986)found no correlation between personality dimensions

and post-operative gallbladder pain. It should be men-

tioned that pain assessment was performed by different

methodologies in different studies and that the person-

ality questionnaire was not always completed at the

same point in time, which may account for conflicting

results.

Fig. 3. Pain perception in the four subgroups based on combined HA and RD scores. Highest pain perception (dark gray) in high HA/low RD

subgroup; lowest pain perception (white) in low HA/low RD subgroup, and intermediate perception in the other two subgroups (light gray).

36 D. Pud et al. / European Journal of Pain 8 (2004) 31–38

According to the results of the present study, indi-

viduals with a high score of HA in combination with a

low score of RD appear to be the most responsive topain, whereas those with a low score of HA and a low

score of RD appear to be the least responsive to pain.

The principal factor that seems to determine pain per-

ception is the scoring of HA. HA individuals tend to be

fearful and anticipate harm even under supportive cir-

cumstances, are typically pessimistic and inhibited by

unfamiliar situations, and generally avoid taking risks.

High scores on this trait seem to predict high pain per-ception, as reflected in our results showing higher pain

perception in high HA volunteers.

According to Cloninger�s theory, individuals with low

RD scores are typically independent and non-conform-

ist, socially detached, unwilling to share their intimate

feelings with others, content to be alone, cynical and

insensitive to social cues and pressures, and only mini-

mally motivated to please others. It may be that low RDserves to unmask pain behavior from possible social and

cultural biases, thereby allowing the HA trait to emerge

as a �net� expression. Thus, Cloninger�s suggested traits

do indeed seem to be relevant to pain perception.

However, further studies are needed to support these

preliminary findings.

In parallel to this psychological rationale, a neuro-

chemical explanation can also be formulated, although

facing the complexity of personality and behavior, re-lating the latter to measures such as levels of specific

neurotransmitters might be an oversimplification of

these mechanisms. Several studies have examined the

relations between the Cloninger personality dimensions

in healthy volunteers and brain neurotransmitters.

Hansenne and Ansseau (1999) found a relationship be-

tween harm avoidance scores and serotonin by showing

a correlation between HA scores and prolactin responseto intra-venous Flesinoxan (5-HT1A agonist) in healthy

volunteers. Garvey et al. (1996) demonstrated a positive

correlation between urinary noradrenaline metabolite

level (HMPG) and reward dependence scores. Gerra

et al. (2000) demonstrated positive correlations between

each specific personality trait (NS, HA, and RD) and

dopaminergic, serotonergic and noradrenergic functions

in healthy subjects by challenging the monoamine sys-tems with specific agonists (bromocriptine, DD-fenflur-

amine, and clonidine, respectively). These findings

support the suggested relations between neurotransmit-

ters and personality traits, as proposed by Cloninger.

The neuro-chemical explanation for our findings

points to serotonin as the main neurotransmitter. We

D. Pud et al. / European Journal of Pain 8 (2004) 31–38 37

suggest that the level of serotonin determines the basicperception of pain. Accordingly, higher levels of sero-

tonin predict high pain responsiveness and vice versa.

Serotonin serves as the main neurotransmitter in the

descending pain inhibitory pathways (Fields and Bas-

baum, 1999). As such, one would expect high levels of

serotonin to express a higher degree of inhibition, re-

sulting in less pain.

Our results, however, indicate higher pain respon-siveness in high HA subjects. A possible explanation

relates to the model suggested by Liu et al. (2000). Ac-

cording to this model, brainstem interneurons in the

periaqueductal grey–dorsal raphe nucleus (PAG–DRN)

complex exert serotoninergic inhibition upon the raphe

serotoninergic neurons. The latter send their axons

down the spinal cord and inhibit pain messages at their

entrance to the cord. Thus, a disinhibition effect willcause an overall heightened pain perception in these

subjects.

In conclusion, the present study demonstrates a re-

lationship between personality traits and pain percep-

tion in response to cold stimuli. These findings may

contribute to our understanding of the possible mecha-

nisms underlying individual differences in pain percep-

tion. The results may also indicate that Cloninger�stridimensional personality theory can be used as a tool

for improving pain management. The identification of

specific personality traits that can predict pain percep-

tion will facilitate the design of individually tailored pain

management plans.

Acknowledgements

The study was supported by the Israel Cancer Asso-

ciation, through the Raya (Rela) Golambo MemorialFund Grant No. 20000009-c.

References

al�Absi M, Buchanan TW, Marrero A, Lovallo WR. Sex differences in

pain preception and cardiovascular responses in persons with

parental history for hypertension. Pain 1999;83:331–8.

American Psychiatric Association. Diagnostic and statistical manual

of mental disorders. 4th ed. Washington, DC: Author; 1994.

Bond MR, Glynn JP, Thomas DG. Relation between pain and

personality in patients receiving pentazocine (Fortral) after sur-

gery. J Psychosom Res 1976;20:369–81.

Brennum J, Kjeldsen M, Jensen K, Jensen TS. Measurements of

human pressure-pain thresholds on fingers and toes. Pain

1989;38:211–7.

Brown RA, Fader K, Barber TX. Responsiveness to pain: stimulus

specificity versus generulity. Psychol Rec 1973;23:1–7.

Chen ACN, Dworkin SF, Haug J, Gehrig J. Human pain responsivity

in a tonic pain model: psychological determinants. Pain

1989;37:143–60.

Chudler EH, Dong WK. The role of the basal ganglia in nociception

and pain. Pain 1995;60:3–38.

Cleeland CS, Nakamura Y, Howland EW, Morgan NR, Edwards KR,

Backonja M. Effects of oral morphine on cold pressor tolerance

time and neuropsychological performance. Neuropsychopharma-

cology 1996;15:252–62.

Cloninger CR. A unified biosocial theory of personality and its role in

the development of anxiety states. Psychiatr Dev 1986;3:167–226.

Cloninger CR. A systemic method for clinical description and

classification of personality variants. Arch Gen Psychiatry

1987;44:573–87.

Cloninger CR, Przybeck TR, Svrakic DM. The tridimensional

personality questionnaire: U.S. normative data. Psychol Rep

1991;69:1047–57.

Ditto B, Edwards MC, Miller S, D�Antono B, Blum S. The effects of

sodium loading on blood pressure and pain responses to the cold

pressor test. J Psychosom Res 1993;37:771–80.

Eckhardt K, Li S, Ammon S, Schanzle G, Mikus G, Eichelbaum M.

Same incidence of adverse drug events after codeine administration

irrespective of the genetically determined differences in morphine

formation. Pain 1998;76:27–33.

Eysenck HJ. Structure of human personality. New York: Wiley; 1960.

Fields HL, Basbaum AI. Central nervous system mechanisms of pain

modulation. In: Wall PD, Melzack R, editors. Textbook of pain.

4th ed. Edinburgh: Churchill Livingstone; 1999. p. 309–30.

Fillingim RB, Maixner W. Gender differences in the response to

noxious stimuli. Pain Forum 1995;4:209–21.

Fillingim RB, Maixner W, Girdler SS, et al. Iscemic but not thermal

pain sensitivity varies across the menstrual cycle. Psychosom Med

1997;59:512–20.

Fromm MF, Eckhardt K, Li S, et al. Loss of analgesic effect of

morphine due to coadministration of rifampin. Pain 1997;72:261–7.

Garcia de-Jalon PD, Jose-Harrison FJ, Johnson KI, Kozma C,

Schnelle K. A modified cold stimulation technique for the

evaluation of analgesic activity in human volunteers. Pain

1985;22:183–9.

Garvey MJ, Noyes Jr R, Cook B, Blum N. Preliminary confirmation

of the proposed link between reward dependence traits and

norepinephrine. Psychiatry Res 1996;65:61–4.

Gerra G, Zaimovic A, Timpano M, Zambelli U, Delsignore R,

Brambilla F. Neuroendocrine correlates of temperamentel traits in

humans. Psychoneuroendocrinology 2000;25:479–96.

Ghione S, Mezzasalma L, Panattoni E. Arterial hypertention is

associated with hypalgesia in humans. Hypertension 1988;12:491–7.

Gil S. The role of personality traits in the understanding of suicide

attempt behavior among psychiatric patients. Arch Suicide Res

2003;7:1–8.

Green JM. Expectations and experiences of pain in labor: findings

from a large prospective study. Birth 1993;20:65–72.

Hansenne M, Pitchot W, Gonzalez-Moreno A, Machurot PY,

Ansseau M. The tridimensional personality questionnaire (TPQ)

and depression. Eur Psychiatry 1998;13:101–3.

Hansenne M, Ansseau M. Harm avoidance and serotonin. Biol

Psychol 1999;51:77–81.

Herran A, Vazquez B. Personality dimensions, the TPQ and depres-

sion. Eur Psychiatry 1998;13:434.

Isselee H, De-Laat A, Lesaffre E, Lysens R. Short-term reproducibility

of pressure pain threshold in masseter and temporalis muscles of

symptom-free subjects. Eur J Oral Sci 1997;105:583–7.

Janssen SA, Arntz A. No interactive effects of naltrexone and

benzodiazepines on pain during phobic fear. Behav Res Ther

1999;37:77–86.

Jones SF, McQuay HJ, Moore RA, Hand CW. Morphine and

ibuprofen compared using the cold pressor test. Pain 1988;34:117–

22.

Keefe FJ, Lefebvre JC, Egert JR, Affleck G, Sullivan MJ, Caldwell DS.

The relationship of gender to pain, pain behavior, and disability in

osteoarthritis patients: the role of catastrophizing. Pain

2000;87:325–34.

38 D. Pud et al. / European Journal of Pain 8 (2004) 31–38

Kleinbohl D, Holzl R, Moltner A, Rommel C, Weber C, Osswald PM.

Psychophysical measures of sensitization to tonic heat discriminate

chronic pain patients. Pain 1999;81:35–43.

Lautenbacher S, Strain F. Sex differences in pain and thermal

sensitivity: the role of body size. Percept Psychophys

1991;50:179–83.

Lautenbacher S, Rollman GB. Sex differences in responsiveness to

painful and non-painful stimuli are dependent upon the stimulation

method. Pain 1993;53:255–64.

Liu R, Thierry J, Aghajanian G. Serotonin 5-HT2 receptors activate

local GABA inhibitory inputs to serotonergic neurons of the dorsal

raphe nucleus. Brain Res 2000;87:334–45.

Lovallo W. The cold pressor test and autonomic function: a review and

integration. Psychophysiology 1975;12:268–82.

Lynn R, Eysenck HJ. Tolerance for pain, extraversion and neuorot-

ioism. Percept Mot Skills 1961;12:161–2.

Martin JE, Inglis J. Pain tolerance and narcotic addiction. Br J Soc

Clin Psychol 1965;4:224–9.

Menza MA, Golbe LI, Cody RA, Forman NE. Dopamine related

personality traits in Parkinson�s disease. Neurology 1993;43:505–8.

Mogil JS. The genetic mediation of individual differences in sensitivity

to pain and its inhibition. Proc Natl Acad Sci USA 1999a;96:7744–

51.

Mogil JS, Wilson SG, Bon K, et al. Heritability of nociception I:

responses of 11 inbred mouse strains on 12 measures of nocicep-

tion. Pain 1999b;80:67–82.

Mogil JS. Individual differences in pain: moving beyond the

‘‘universal’’ rat. Bulletin 1999c;9:12–3.

Nelson E, Cloninger CR. Exploring the TPQ as a possible predictor of

antidepressant response to nefazodone in a large multi-site study.

J Affect Disord 1997;44:197–200.

Nixon SJ, Parsons OA. Cloninger�s tridimensional theory of person-

ality: constract validity in a sample of college students. Pers Indiv

Differ 1989;10:1261–7.

Peckerman A, Hurwitz BE, Saab PG, Llabre MM, Mccabe PM,

Schneiderman N. Stimulus dimensions of the cold pressor test and

the associated patterns of cardiovascular response. Psychophysiol-

ogy 1994;31:282–90.

Phillips JM, Gatchel RB. Extraversion–introversion and chronic pain.

In: Gatchel RB, Weisberg JN, editors. Personality characteristics of

patients with pain. 1st ed. Washington, DC: American psycholog-

ical association; 2000. p. 181–202.

Poulsen L, Arendt-Nielsen L, Brosen K, Nielsen KK, Gram LF,

Sindrup SH. The hypoalgesic effect of imipramine in different

human experimental pain models. Pain 1995;60:287–93.

Riley JL, Robinson ME, Wise EA, Myers CD, Fillingim RB. Sex

differences in the perception of noxious experimental stimuli: a

meta-analysis. Pain 1998;74:181–7.

Russo J, Katon W, Sullivan M, Clark M, Buchwald D. Severity of

somatization and its relationship to psychiatric disorders and

personality. Psychosomatics 1994;35:546–56.

Starcevic V, Vhlenhuth EH, Fallon S, Patha K. Personality dimensions

in panic disorder and generalized anxiety disorder. J Affect Disord

1996;37:75–9.

Taenzer P, Melzack R, Jeans ME. Influence of psychological factors

on post-operative pain, mood and analgesic requirements. Pain

1986;24:331–42.

Thomas T, Robinson C, Champion D, McKell M, Pell M. Prediction

and assessment of severity of post-operative pain and of satisfac-

tion with management. Pain 1998;75:177–85.

Turk DC. Biopsychosocial perspective on chronic pain. In: Gatchel RJ,

Turk DC, editors. Psychological approaches to pain management: a

practitioner�s handbook. New York: Guilford Press; 1996. p. 3–34.

Unruh AM. Gender variations in clinical pain experience. Pain

1996;65:123–67.

Williams DA. Acute pain with special emphasis on painful medical

procedures. In: Gatchel RJ, Turk DC, editors. Psychosocial factors

in pain: clinical perspectives. 1st ed. New York: The Guilford Press;

1999. p. 151–63.

Wolff BB. Methods of testing pain mechanisms in normal man. In:

Wall PD, Melzack R, editors. Textbook of pain. 2nd ed.

Edinburgh: Churchill Livingstone; 1984. p. 186–94.

Yarnitsky D, Sprecher E, Zaslansky R, Hemli JA. Heat pain

thresholds: normative data and repeatability. Pain 1995;60:329–32.

Yarnitsky D, Sprecher E, Zaslansky R, Hemli JA. Multiple session

experimental pain measurement. Pain 1996;67:327–33.

Zamir N, Shuber E. Altered pain perception in hypertensive humans.

Brain Res 1980;201:471–4.

Zar JH. Biostatistical analysis. 2nd ed. New Jersey: Prentice Hall;

1984. p. 236–242.