Journal of Behavioral and Brain Science, 2013, 3, 7-12 Published Online February 2013 (
Assessing the Analgesic Effects of Sucrose to
Cold Pressor Pain in Human Adults
Michele E. Mercer1, Mark D. Holder2
1Department of Psychology, Memorial University of Newfoundland, St. John’s, Canada
2Department of Psychology, University of British Columbia, Kelowna, Canada
Received December 28, 2012; revised January 5, 2012; accepted February 18, 2012
Previous studies report that the ingestion of highly concentrated sweet solutions produces a morphine-like analgesia in
rats, human infants, and in adult males. To determine whether sweet-induced analgesia occurs with more commonly
consumed substances, 30 adult males (Mage = 22.4 years) were exposed to a cold pressor test and pain responsivity was
assessed both before and after consuming either an 8% sucrose solution, water, or nothing. Between-groups compari-
sons revealed that re lative to the Sucrose or N othing groups, the Water g roup showed increased pa in tolerance. Neither
pain thresholds nor ratings of pain intensity and unpleasantness on a visual analogue scale differed among groups. The
results support previous findings in bo th humans and animals that the palatab ility or hedonic valu e of food or drink may
be the key predictor of its analgesic effect.
Keywords: Sucrose; Analgesia; Pain; Cold Pressor; Humans
1. Introduction
The vertebrate endogenous opioid system plays a role in
food consumption, particularly in the ingestion of palat-
able sweet foods [1]. For example, in humans and other
animals, the administration of an opioid agonist (e.g.,
morphine) increases both the intake of and preference for
sucrose [2], whereas an opioid antagonist (e.g., naltrex-
one) produces opposite effects [3]. The reciprocal rela-
tionship also exists; the consumption of sweet ingesta in-
creases endogenous opioid peptide (EOP) activity in rat
brain, plasma and cerebral spinal fluid [4-6], and also
human plasma [7].
Because EOPs decrease pain, the effect of sweet in-
gestion on pain responsivity has been examined [8]. Stu-
dies show that intraoral sweet solutions (either dextrose/
saccharin or sucrose) increase rats’ paw-lift latencies from
a hot-plate [8-10], an analgesic effect resembling that
produced by morphine. Moreover, this sweet-induced
analgesia (SIA) is reversed by minimal doses of opioid
antagonists (e.g., naltrexone, naloxone) suggesting that
EOPs mediate the analgesic effect [8,9,11]. Sweet intake
appears to produce analgesia in human infants as well
[12-15]. For example, as little as 2 ml of a 12% sucrose
solution markedly reduces crying in newborn infants
during both circumcision and heel lance procedures [13].
Moreover, the rapid onset of the analgesic effect suggests
that it is produced by the sweets’ pleasant taste rather
than by its chemical composition or by some post-inges-
tive factor [6,12,13].
We know little about whether SIA persists beyond in-
fancy. One study investigated the effects of the taste of
sucrose on pain responsivity to a cold pressor test (CPT)
in 8 to 11-year-old children [16]. Relative to water, su-
crose increased children’s pain threshold, but had no af-
fect on pain tolerance or pain intensity ratings. A more
recent study [17] examined SIA in both 5 to 10-year-old
children and their mothers’ responses to cold pressor
pain. They found that sucrose increased pain threshold
and tolerance of children, but not those of women. The
absence of SIA in adults (women) is consistent with re-
sults showing that rat SIA progressively declines with
age and is absent by the 3rd week of life [9]. However,
much more evidence is required before we can determine
whether SIA persists into human adulthood. Of particular
interest is to determine whether this effect might be more
apparent in men. A recent series of studies by Kakeda
and colleagues [18-20] reported that after ingestion of a
24% sweet solution, CPT pain thresholds increased in
adult males, but not in females. Interestingly however,
they found th at there was no effect on pain tolerance bu t
conceded that the lack of pain tolerance may have been
constrained by a ceiling effect, as more than one third of
subjects endured the limited duration (3 min) of cold
pressor exposure.
The present study attempts to improve upon previous
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CPT experiments in several important ways. First, to re-
duce ceiling effects and thus better examine effects on
pain tolerance, subjects were able to immerse their hand
in cold water for a maximum of 5 minutes. Coupled with
the above reported effects on pain threshold [18-20], full
assessment of pain tolerance allows us to better under-
stand whether the analgesic effect is opioid-mediated as
sweets are suspected to modulate the affective dimen-
sions of pain (e.g. tolerance) rather than the sensory com-
ponents of pain (e.g., threshold) [21,22]. Second, to bri-
dge the gap between lab-based experiments and real life
conditions, our experimental paradigm attempts to better
test the robustness of the SIA effect as well as better rep-
licate the real world ingestion of sweet substances in
several important ways: 1) by providing a sucrose solu-
tion (8%) that better represents the sugar content (6% to
12%) of everyday sweet beverages (e.g., soda, juice,
sports drinks); 2) by providing an amount of beverage
(100 ml) that better approximates the average dose con-
sumed by individuals everyday; and 3) by allowing sub-
jects to fully consume the beverage just prior to pain as-
sessment. This would also allow us to more thoroughly
evaluate sucrose’s effect on pain tolerance, as the orogu-
statory (opioid-mediated) effects of sucrose have a slower
onset and later offset than the immediate and stimulus-
bound orotactile (nonopioid-mediated) effects [12]. Fi-
nally, unlike other CPT studies, we measure both pain
and tactile thresholds, before and after treatment. This
allows us to distinguish whether sucrose modulates the
pain system exclusively, and/or has more general effects
on other related sensory systems. In sum, the importance
of studying SIA in adults is to provide us with a better
understanding of our intrinsic pain-inhibitory systems
and of the environmental conditio ns which activate these
systems, and thus, perhaps more effective approaches to
the treatment of pain.
2. Methods
2.1. Subjects
The subjects were 30 right-handed, non-smoking, pain-
free male university students (Mage = 22.4 yrs; range = 18
- 39 yrs) recruited by signs placed around campus. Sub-
jects were contacted by phone, debriefed about the ex-
perimental procedure, and asked to abstain from alcohol
and analgesics during the test day, and from eating or
drinking anything for at least one hour prior to the ex-
perimental session. This duration for food deprivation
was used so that subjects did not consume sweets prior to
baseline testing. Longer deprivation periods were not
used in an attempt to avoid deprivation-induced analgesia
[23]. Only non-smoking, right-handed, male subjects
were chosen for several reasons: 1) because smoking re-
duces pain sensitivity [24]; 2) because left limbs show
greater pain sensitivity than right limbs regardless of
hand preference [25]; and 3) because females’ hormonal
cyclicity produces v ariability in pain sensitivity [26 ]. The
study protocol conformed to the provisions of the decal-
ration of Helsinki and was approved by the Memorial
University Faculty of Science Co mmittee for Human Re-
2.2. Apparatus
The cold pressor consisted of a 45.5 × 24.5 × 21 cm
Plexiglas tank (a modified rat laboratory cage) filled with
ice water (depth = 15 cm). A wire mesh screen divided
the tank so that one section (45.5 × 6.5 × 21 cm) con-
tained crushed ice and the other section (45.5 × 18 × 21
cm) contained ice-free water. The water temperature was
monitored with a digital display thermometer, and the
water was circulated continuously with a submersible
aquarium water pump (120 V; output = 480 lph) in order
to maintain a water temperature between 0 and 1.5˚C (M
= 0.83; SD = 0.28). Tactile thresholds were measured
with a 20-monofilament Von Frey kit (Stoelting, Co.,
Wood Dale, IL). A curtain was used to shield the sub-
jects from both the cold pressor and the monofilaments.
A carbon-filtered water purifier was used to reduce im-
purities and to remove any odor or taste from the water
comprising the treatment solutions.
2.3. Procedures
Subjects were randomly assigned to one of three treat-
ment groups that differed according to whether they were
to consume an 8% sucrose solution (Sucrose group, n =
10), purified tap water (Water group, n = 10), or nothing
(Nothing group, n = 10). [Note that the 8% sucrose solu-
tion was comprised of sucrose and purified tap water.]
Power analyses conducted previously on pilot data col-
lected in our laboratory determined that a sample size of
10 per group was sufficient to detect an experimental
treatment effect at the p = 0.01 level [27]. For each group,
pain and tactile sensitivity were measured both before
(the pre-treatment phase) and after (the post-treatment
phase) treatment.
Each subject was tested individually in the laboratory.
The experimenter first described the intensity and un-
pleasantness visual analogue scales (VASs) using the ins-
tructions and auditory analogy described initially by
Price et al. [22]. Each scale was represented by a vertical
line consisting of 20 divisions ranging from either “No
sensation” (the intensity VAS) or “Not bad at all” (the
unpleasantness VAS) to either “Most in tense th at one can
imagine” or “Most unpleasant that one can imagine”. To
familiarize subjects with the VASs and to ensure that
they were not experiencing any discomfort prior to the
experiment, subjects were asked to rate their current level
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of discomfort using both VASs. Testing proceeded in
three phases.
The pre-treatment phase. Subjects were instructed to
place their left hand and forearm in the 0˚ - 1˚ cold pres-
sor. Pain responsivity was assessed with two laten cy me a -
sures, pain threshold and pain tolerance. Subjects were
asked to inform the experimenter when they first felt pain
(threshold), and then to remove the forearm when the
pain became too uncomfortable to be continued (toler-
ance). If the subject failed to withdraw his arm from the
CPT after 5 minutes had passed, the experimenter in-
structed the subject to remove his arm. Immediately after
the subject removed his arm, he rated the intensity and
unpleasantness of his pain using the two VASs.
Following pain measurement, pre-treatment tactile sen-
sitivity was assessed with a graded series of calibrated
nylon monofilaments (von Frey fibres). The monofila-
ments were applied to the area between the thumb and
index fing er on the dorsal sid e of the subj ect’s right han d
(the hand not exposed to the CPT). Tactile thresholds,
defined as the minimal force required for the subject to
detect a fibre on three consecutive trials, were estimated
using a standard staircase procedure.
The treatment phase. Subjects in the Sucrose and Wa-
ter Groups were administered the appropriate solution
(100 ml) using the following standardized procedure:
Every two minutes during a 10-minute period, the subject
was instructed to ingest 20 ml of the solution by swish ing
it around in his mouth for on e minute pr io r to swallow ing
it. Subjects in the Nothing Group were instructed to sit
and read a selected passage from a psychology textbook
for 10 minutes.
The post-treatment phase. Immediately following treat-
ment, subjects’ pain and tactile sensitivity were assessed
again by exposing them to the CPT followed by the
monofilaments. After the experimental phase was termi-
nated, all subjects completed a personal questionnaire
intended to provide information about each subject’s re-
cent experience with factors which may modulate pain
responsivity (e.g., medication, smoking, alcohol) [28]. All
sessions occurred between 1400 and 1700 h and lasted
between 35 and 45 m inutes.
3. Results
3.1. Analysis of Group Differences
One-way analyses of covariance (ANCOVAs) comparing
the groups at post-treatment (the pre-treatment phase
scores served as the covariate) were performed on each
of the four pain measur es, and on tactile th resho ld s. If the
sucrose produced analgesia to the pain induced by the
CPT, then at post-treatment, subjects who received the
sucrose should show elevated pain thresholds, pain tol-
erances, and/or decreased VAS ratings of pain intensity
or unpleasantness, relative to subjects receiving water or
nothing. Post-treatment tactile thresholds should not dif-
fer among groups.
One-way ANCOVAs revealed a significant group (i.e.,
treatment) difference for pain tolerance [F (2,26) = 3.84,
p = 0.035]. However, post-hoc comparisons revealed a
surprising result. As Table 1 illustrates, post-treatment
pain tolerance was significantly higher for the Water
group than for the o ther two groups (N ewman-K euls, p <
0.05). Furthermore, the omega squared value for this
effect was 0.159, a statistic which indicates a “strong”
experimental effect [27]. This result suggests that even
for this relatively small sample size (n = 10 per group),
there was adequate statistical power to detect an experi-
mental effect, g iven that one existed. Groups d id not dif-
fer on any of the other pain measures, or on tactile thre-
sholds (all p > 0.05).
3.2. Correlations between Pain Measures and
Subject Variables
To determine whether there were any relationships be-
tween the latency pain measures (threshold and toler-
ance), between the VAS pain measures (intensity and un-
pleasantness), or between the four pain measures and any
of the recorded subject variables (e.g., body weight,
amount of exercise), Pearson product-moment correla-
tions were conducted. As expected, intensity and unplea-
santness measures were correlated at pre-treatment (r =
0.77, p < 0.05) as were measures of pain threshold and
tolerance (r = 0.46, p < 0.05). However, there were no
Table 1. Adjusted post-treatment means (M) and standard errors (SEM) of each pain and tactile measure for each treatment
group [*denotes the group that differed from the other groups in that column (p < 0.05)].
Group Threshold (sec) Tolerance (sec) Intensity (0 - 20) Unpleasantness (0 - 20) Tactile Threshold
Nothing 16 (9) 63 (18) 13.1 (1.6) 11.9 (1.9) 3.31 (0.08)
Water 17 (3) 103* (35) 12.5 (1.3) 13.1 (1.3) 3.45 (0.16)
Sucrose 18 (4) 57 (8) 13.7 (1.1) 14.8 (1.1) 3.30 (0.07)
significant correlations between any of the outcome pain
measures and any of the subject variables (all ps > 0.05),
thus suggesting that any pre-existing subject conditions
(e.g., exercise, alcohol consumption, sweet intake history,
sexual activity) had little effect upon the results.
4. Discussion
Unlike reports of sweet-induced analgesia in neonatal
rats and human infants, the present results show little
evidence of this effect in human adult males. Failure to
find SIA for cold pressor pain has also been reported
consistently for adult women [17,18] In addition, the
apparent absence of SIA in men is consistent with results
from our previous study of mechanically-induced pain
(pressure algometry) in men [29]. Thus, the present re-
sults raise new issues within the area of pain and inges-
tion. One consideration is that SIA in humans does not
persist into adulthood (but see [30]). SIA may diminish
with age because it no longer serves a biological advan-
tage (such as for mother-infant attachment or for energy
conservation) [31,32]. Studies with rats suggest that SIA
is limited to the pre-weaning period, and may be a de-
velopmentally transient phenomenon [9,11]. Alterna-
tively it may be that with age, human SIA decreases be-
cause of permanent changes to the endogenous opioid
system as a result of health [17,22,33] and/or experien-
tial/environmental factors [9,24].
A second consideration is that SIA does exist in hu-
man adults but is not observable under all experimental
pain procedures. For ethical reasons, human adults, un-
like rats or human infants, must be informed that they
can remove the pain stimulus at any time. Therefore, the
pain is always viewed as being “escapable” or “control-
lable”. This information may serve as a safety signal
which may trigger a CNS antianalgesia mechanism (e.g.,
CCK), and thus attenuate any analgesic effect of the su-
crose [34].
Our findings showing the lack of apparent SIA in adult
males are however somewhat at odds with recent work
[18-20] which found in several CPT experiments, that a
24% sucrose solution increased pain threshold (but usu-
ally not pain tolerance) in adult males. One argument
might be that our group sizes (n = 10) lack the statistical
power to detect an effect, although this seems unlikely
given the effect size analyses reported in the previous
section. Moreover, those who have used the CPT [18-20]
and found evidence of SIA did so with similar small
samples of adults. Another explanation for the differ-
ences among results may be that SIA is perhaps not a
robust effect and is eviden t only under certain conditions
(e.g., higher concentrations of sucrose). Alternatively,
SIA is perhaps only a short-term orotactile effect which
may influence adult p ain threshold but not pain to lerance,
arguably the more important clinically of the two meas-
ures. The methodological differences between studies
(e.g., sucrose concentration, ingestion procedure, cultural
factors, and time limits) allude to the suggestion that SIA
may thus be an environmental/situational specific effect,
at least for cold pressor pain.
Although any of the above arguments may account for
the absence of sweet-induced analgesia in the present
study, they do not explain the relative analgesia shown
by the water group in the present study. Subjects who
consumed only the purified tap water showed increased
pain tolerance compared to those who consumed nothing,
or even the 8% sucrose solution (sucrose mixed with
purified tap water). These apparently paradoxical results
leave us with the interesting suggestion that any findings
of oral-based analgesia are not due to sweet per se, but
instead, are associated more specifically with the palat-
ability (or reward value) of the ingesta. Although the 8%
solution used in th e present study falls with in th e average
range of sucrose concentrations (7% - 10%) apparently
preferred by adults [35], most subjects in the current
study described the 8% sucrose solution as being “too
sweet” or “sickeningly sweet” and thus, relatively unpal-
atable. On the other hand, because the subjects were
slightly water-deprived and perhaps nervous under these
conditions, the water may have tasted more palatable
than the sucrose so lution. Note th at even though previou s
studies [18-20] used sucrose concentrations even higher
than ours (24% vs 8%) and found evidence of threshold
SIA, subjects under the conditions of those studies rated
the pleasantness of this sweet taste (and thus its palatabi-
lity) significantly higher than water. Collectively, these
opposing results appear to suggest that palatability may
be the critical factor in eliciting the release of opioids and
thus the produc ti on of anal gesia.
Indeed, results from several other lines of research
support the hypothesis that it may the positive hedonic
value of the sucrose, and not the sweetness or the caloric
content of the ingesta, which mediates SIA [3,5,6,17,30,
36,37]. For instance, in a series of well controlled studies,
Foo and Mason [36] showed that experimental manipula-
tions of the palatability o r hedonic value of ing ested sub-
stances (e.g., chocolate, water, sucrose) consistently pre-
dicted the analgesic effects in rats. For example, when
the hedonic value of these normally palatable foods is
compromised by either a conditioned taste aversion or
naltrexone injections, the analgesic effect is weakened.
Moreover, when the hedonic value of water is increased
(as in water-deprivation or LPS induced illness), water
alone has been also shown to increase CSF and plasma
EOP levels [5] and produce analgesia in rats [36]. Our
results with human males suggest that the hedonics/pal-
atability of the ing esta may also play a significant role in
human response to pain. Therefore, future studies of SIA
Copyright © 2013 SciRes. JBBS
with human adults should examine the specific role that
food palatability plays in inducing analgesia. Only then
can we determine whether SIA (or perhaps, palatability-
induced analgesia) is an enduring characteristic of the
human CNS, and perhaps more importantly, may help in
the alleviation of pain during clinical procedures. If so, it
may be possible to establish the specific conditions under
which individuals may self-medicate with preferred and
palatable substances in order to mitigate pain during me-
dical and non-medical procedures.
5. Acknowledgements
This research was supported by Natural Sciences and
Engineering Research Council of Canada (NSERC) op-
erating grant (A1221) to M. Holder, and by fellowships
from NSERC and the Women’s Association of Memorial
University to M. Mercer. We thank Catherine Hynes and
Tanya Davis for assistance with the data collection.
[1] A. S. Levine and C. J. Billington, “Opioids. Are They
Regulators of Feeding?” Annals of the New York Acad-
emy of Sciences, Vol. 575, No. 1, 1989, pp. 209-220.
[2] S. A. Czirr and L. D Reid, “Demonstrating Morphine’s
Potentiating Effects on Sucrose-Intake,” Brain Research
Bulletin, Vol. 17, No. 5, 1986, pp. 639-642.
[3] M. J. Fantino, J. Hosotte and M. Apfelbaum, “An Opiate
Antagonist, Naltrexone Reduces Preference for Sucrose
in Humans,” American Journal of Physiology, Vol. 251,
No. 1, 1986, pp. R91-R96.
[4] J. Dum, C. Gramsch and A. Herz, “Activation of Hypo-
thalamic Beta-Endorphin Pools by Reward Induced by
Highly Palatable Food,” Pharmacology Biochemistry and
Behaviour, Vol. 18, No. 3, 1983, pp. 443-447.
[5] T. Yamamoto, N. Sako and S. Maeda, “Effects of Taste
Stimulation on Beta-Endorphin Levels in Rat Cerebro-
spinal Fluid and Plasma,” Physiology and Behavior, Vol.
69, No. 3, 2000, pp. 345-350.
[6] T. Yamamoto, “Brain Mechanisms of Sweetness and Pa-
latability of Sugars,” Nutrition Reviews, Vol. 61, No. 5,
2003, pp. S5-S9. doi:10.1301/nr.2003.may.S5-S9
[7] J. C. Melchior, D. Rigaud, N. Colas-Linhart, A. Petiet, A.
Girard and M. Apfelbaum, “Immunoreactive Beta-Endor-
phin Increases after an Aspartame Chocolate Drink in
Healthy Human Subjects,” Physiology and Behavior, Vol.
50, No. 5, 1991, pp. 941-944.
[8] E. M. Blass, E. Fitzgerald and P. Kehoe, “Interactions
between Sucrose, Pain and Isolation Distress,” Pharma-
cology Biochemistry and Behaviour, Vol. 26, No. 3, 1987,
pp. 483-489. doi:10.1016/0091-3057(87)90153-5
[9] V. C. Anseloni, H. R. Weng, R. T erayama, D. Letizia, B.
J. Davis, K. Ren, et al., “Age-Dependency of Analgesia
Elicited by Intraoral Sucrose in Acute and Persistent Pain
Models,” Pain, Vol. 97, No. 1-2, 2002, pp. 93-103.
[10] M. D. Holder, “Responsivity to Pain in Rats Changed by
the Ingestion of Flavoured Water,” Behavioral and Neu-
ral Biology, Vol. 49, No. 1, 1988, pp. 45-53.
[11] F. N. Segato, C. Castro-Souza, E. N. Segato, S. Morato,
and N. C. Coimbra, “ Sucrose Ingestion Causes Opioid
Analgesia,” Brazilian Journal of Medical and Biological
Research, Vol. 30, No. 8, 1997, pp. 981-984.
[12] R. G. Barr, M. S. Pantel, S. N. Young, J. H. Wright, L. A.
Hendricks and R. Gravel, “The Response of Crying New-
borns to Sucrose: Is It a ‘Sweetness’ Effect?” Physiology
and Behavior, Vol. 66, No. 3, 1999, pp. 409-417.
[13] E. M. Blass and L. B. Hoffmeyer, “Sucrose as an Analge-
sic for Newborn Infants,” Pediatrics, Vol. 87, No. 2, 1991,
pp. 215-218.
[14] B. A. Smith, T. J. Fillion and E. M. Blass, “Orally-Me-
diated Sources of Calming in One to Three-Day-Old Hu-
man Infants,” Developmental Psychology, Vol. 26, No. 5,
1990, pp. 731-737. doi:10.1037/0012-1649.26.5.731
[15] B. Stevens, J. Yamada and A. Ohlsson, “Sucrose for An-
algesia in Newborn Infants Undergoing Painful Proce-
dures,” Cochrane Database of Systematic Reviews, Vol. 1,
No. 1, 2010, Article ID: CD001069.
[16] A. Miller, R. G. Barr and S. N. Young, “The Cold Pressor
Test in Children: Methodological Aspects and the Anal-
gesic Effect of Intraoral Sucrose,” Pain, Vol. 56, No. 2,
1994, pp. 175-183. doi:10.1016/0304-3959(94)90092-2
[17] M. Y. Pepino and J. A. Mennella, “Sucrose-Induced An-
algesia Is Related to Sweet Preferences in Children but
Not Adults,” Pain, Vol. 119, No. 1, 2005, pp. 210-218.
[18] T. Kakeda and T. Ishikawa, “Gender Differences in Pain
Modulation by a Sweet Stimulus in Adults: A Random-
ized Study,” Nursing and Health Sciences, Vol. 13, No. 1,
2011, pp. 36-40. doi:10.1111/j.1442-2018.2010.00573.x
[19] T. Kakeda, “Potential of Sucrose-Induced Analgesia to
Relieve Pain in Male Adults: A Preliminary Study,” Ja-
pan Journal of Nursing Science, Vol. 7, No. 2, 2010, pp.
169-173. doi:10.1111/j.1742-7924.2010.00150.x
[20] T. Kakeda, M. Ito, T. Matsui and T. Ishikawa, “The Evi-
dence for Sweet Substance-Induced Analgesia in Adult
Human,” Pain Research, Vol. 23, No. 3, 2008, pp. 159-
[21] M. D. Lewkowski, B. Ditto, M. Roussos and S. N. Young,
“Sweet Taste and Blood Pressure-Related Analgesia,”
Pain, Vol. 106, No. 1, 2003, pp. 181-186.
[22] D. D. Price, P. A. McGrath, A. Rafii and B. Buckingham,
“The Validation of Visual Analogue Scales as Ratio Scale
Measures for Chronic and Experimental Pain,” Pain, Vol.
17, No. 1, 1983, pp. 45-56.
Copyright © 2013 SciRes. JBBS
Copyright © 2013 SciRes. JBBS
[23] K. K. Vaswani and G. A. Tejwani, “Food Deprivation-In-
duced Changes in the Level of Opioid Peptides in the Pi-
tuitary and Brain of Rat,” Life Sciences, Vol. 38, No. 2,
1986, pp. 197-201. doi:10.1016/0024-3205(86)90012-3
[24] O. F. Pomerlau, D. C. Turk and J. B. Fertig, “The Effects
of Cigarette Smoking on Pain and Anxiety,” Addictive
Behaviors, Vol. 9, No. 3, 1984, pp. 265-271.
[25] S. Johnson, “The Evaluation of Pain in Man,” Frontiers
of Pain, Vol. 2, 1974, pp. 1-3.
[26] P. Goolkasian, “Cyclic Changes in Pain Perception: An
ROC Analysis,” Attention, Perception and Psychophysics,
Vol. 27, No. 6, 1980, pp. 499-504.
[27] G. Keppel and T. Wilkins, “Design and Analysis,” 5th
Edition, Prentice Hall, Upper Saddle River, 2007.
[28] E. G. Hapidou and D. De Catanzaro, “Sensitivity to Cold
Pressor Pain in Dysmenorrheic and Non-Dysmenorrheic
Women as a Function of Menstrual Cycle Phase,” Pain,
Vol. 34, No. 3, 1988, pp. 277-283.
[29] M. E. Mercer and M. D. Holder, “Antinociceptive Effects
of Palatable Sweet Ingesta on Human Responsivity to
Pressure Pain,” Physiology and Behavior, Vol. 61, No. 2,
1997, pp. 311-318. doi:10.1016/S0031-9384(96)00400-3
[30] M. Bhattacharjee, R. Bhatia and R. Mathur, “Gender Spe-
cificity of Sucrose Induced Analgesia in Human Adults,”
Indian Journal of Physiology and Pharmacology, Vol. 51,
No. 4, 2007, pp. 410-414.
[31] E. M. Blass, “The Ontogeny of Motivation: Opioid Bases
of Energy Conservation and Lasting Affective Change in
Rat and Human Infants,” Current Directions in Psycho-
logical Science, Vol. 1, No. 4, 1992, pp. 116-120.
[32] P. Kehoe and E. M. Blass, “Opioid Mediation of Separa-
tion Distress in 10-Day-Old Rats: Reversal of Stress with
Maternal Stimuli,” Developmental Psychobiology, Vol.
19, No. 4, 1986, pp. 385-398.
[33] S. Bruel and O. Y. Chung, “Interactions between the Car-
diovascular and Pain Regulatory Systems: An Updated
Review of Mechanisms and Possible Alterations in Chro-
nic Pain,” Neuroscience and Biobehavioral Reviews, Vol.
28, 2004, pp. 395-414.
[34] E. P. Wiertelak, S. F. Maier and L. R. Watkins, “Chole-
cystokinin Anti-Analgesia: Safety Cues Abolish Morphine
Analgesia,” Science, Vol. 256, No. 5058, 1992, pp. 830-
833. doi:10.1126/science.1589765
[35] H. R. Moskowitz, R. A. Kluter and H. L. Jacobs, “Sugar
Sweetness and Pleasantness: Evidence for Different Psy-
chological Laws,” Science, Vol. 184, No. 4136, 1974, pp.
583-585. doi:10.1126/science.184.4136.583
[36] H. Foo and P. Mason, “Analgesia Accompanying Food
Consumption Requires Ingestion of Hedonic Foods,” The
Journal of Neuroscience, Vol. 29, No. 41, 200 9, pp. 13053-
13062. doi:10.1523/JNEUROSCI.3514-09.2009
[37] L. A. Ramenghi, D. J. Evans and M. I. Leave, “Sucrose
Analgesia: Absorptive Mechanism or Taste Perception?”
Archives of Disease in Childhood-Fetal and Neonatal
Edition, Vol. 80, No. 2, 1999, pp. F146-F147.