It is well known that the taste of sweet solutions produces a morphine-like analgesia in both rats and human infants, and under certain conditions, possibly in human adults. To further explore whether ingestion analgesia persists into human adulthood, the present study was the first to utilize contact heat, a method of pain induction used commonly in both behavioural and pharmacological studies with laboratory animals. Left arms of 120 university undergraduates were exposed to a hot-plate, with pain responsivity assessed both before and after consuming either nothing (control group), or foods that they rated previously as unpalatable (e.g., black olives), neutral (e.g., rice cakes), or palatable (e.g., chocolate-chip cookies). Pain responsivity was assessed with four pain measures: pain threshold, pain tolerance, and visual analogue scale (VAS) ratings of pain intensity and unpleasantness. Between-groups comparisons in 2 separate experiments revealed that women (but not men) who consumed a palatable food showed increased pain tolerance, relative to the nothing, unpalatable, or neutral groups. Collectively, these data support our previous findings that “palatability-induced analgesia” exists in human adults, at least in females. Moreover, the findings support contact heat as a suitable method for assessing ingestion analgesia to experimental pain with human adults.
It is now well established that the consumption of sweet ingesta increases endogenous opioid peptide (EOP) activity in rat brain, plasma and cerebral spinal fluid, as well as in human plasma [
Sweet intake appears to produce analgesia in human infants as well [
At present, several researchers are examining whether this relationship between sweets and analgesia also exists in human adults. Of the few studies which have investigated SIA in adulthood, most have used the cold pressor test (CPT) [
Collectively, these findings from CPT studies suggest that sweet-induced analgesia may occur in human adults, but it may be limited by a number of experimental parameters, namely subject gender, method of pain induction, and specific pain measures. There are few experiments that have used methods other than the CPT to explore SIA in human. One exception is a study [
The present study is designed for two reasons, namely to use an alternative method to determine whether SIA occurs in human adults, and to examine more specifically, the effects that palatability has on the relationship between ingestion and analgesia. Interestingly, researchers examining human pain responsivity have yet to utilize the method first used to demonstrate SIA in rats, namely contact heat [
EXPERIMENT 1
In previous work with both cold and pressure modes of pain [
The subjects were 40 Caucasian, right-handed, non-smoking, pain-free female university students (M age = 20.7; range = 18 - 38). An additional 2 subjects were tested but not included in the final sample; 1 because she did not follow proper procedural instructions, and 1 because she kept her forearm on the hot-plate at the maximum temperature of 48.0˚C during the pre-treatment trial (i.e., she showed the maximum tolerance). Subjects were recruited by signs placed around campus and then contacted by phone and briefed about the experimental procedure. Prospective subjects were asked to abstain from alcohol and analgesics during the test day, and from eating or drinking anything for at least 2 hours prior to the experimental session. This duration for food deprivation was used so that subjects did not consume palatable foods prior to baseline testing. Longer deprivation periods were not used in an attempt to avoid deprivation-induced analgesia [
A laboratory hot-plate (Socrel corp. model DS37) was used to apply contact heat to the subjects’ left forearm. The hot-plate consists of a 20 × 20 cm metal plate connected to a variable DC power supply. The apparatus displays the surface temperature of the metal plate in digital 0.1˚C increments. Once the hot-plate is turned on, the temperature of the metal plate increases at a consistent rate of 1.0˚C per 15 s until it reaches 48.0˚C. To evaluate whether ingestion modulates the pain system exclusively, and/or has more general effects on related sensory systems, tactile thresholds were measured with a 20-monofilament Von Frey kit (Stoelting, Co., Wood Dale, IL). A curtain was used to shield the subjects from both the hot-plate and the monofilaments.
Prior to the laboratory session, subjects were contacted by phone and asked to rate the palatability of 10 foods on a 10-point scale with 1 indicating “Strongly Dislike” and 10 indicating “Strongly Like”. It is interesting to note that the ratings for many of foods, including all of those targeted for the study, were highly consistent among subjects. Because of this commonality of hedonic response, subjects were assigned in pseudorandom fashion to one of four treatment groups: “Palatable” (composed of 10 Ss who all rated chocolate chip cookies between 8 and 10), “Neutral” (composed of 10 Ss who all rated rice cakes between 4 and 6), “Unpalatable” (composed of 10 Ss who all gave black olives a rating of 1 or 2), or “Nothing” (n = 10; composed of every 4th subject selected, irrespective of her food ratings. Both pilot work and our previous studies [
For each group, a within-subjects design was used in which both pain and touch sensitivity of each subject were measured three times (i.e., during familiarization, pre-treatment, and post-treatment). However, the familiarization trial was excluded from the data analyses as this trial served to warm up each subject’s arm to a similar temperature prior to collecting data, as well as to give the subjects practice with the procedure and to ensure that they understood all of the instructions.
Subjects were tested individually in the laboratory. The experimenter, who was blind to the hypothesis of the experiment, first described the pain intensity and unpleasantness visual analogue scales (VASs) using the instructions and auditory analogy described originally by Price, McGrath, Rafii, and Buckingham [
Testing proceeded in 4 phases: Familiarization, Pre-treatment, Treatment, and Post-treatment.
The Familiarization and Pre-treatment Trials: The hot-plate was activated and once it reached a temperature of 43.0˚C, subjects were instructed to immediately place their left forearm firmly on the hot-plate. Subjects were instructed to say “pain” when they first felt pain (threshold) and to say “stop” when the pain became too uncomfortable to continue (tolerance). Threshold and tolerance were recorded at the precise temperatures to which the subjects reported “pain” and “stop”. To prevent injury, if the subjects did not say “stop” before the hot- plate’s temperature reached 48.0˚C, they were told to remove their arm from the heat. In addition, immediately following the removal of their arm, subjects were instructed to rate the intensity and unpleasantness of the pain at the instant that they reported “stop”.
Following pain measurement, pre-treatment tactile sensitivity was measured. A graded series of calibrated nylon monofilaments (von Frey fibers) were applied to the area between the thumb and index finger on the dorsal side of the right hand (the hand not exposed to the heat). 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 method.
The Treatment Trial: Subjects in the Palatable, Neutral, and Unpalatable groups then consumed a chocolate chip cookie, a rice cake, or a black olive, respectively. Subjects in the Nothing (control) group did not consume anything. Instead, they were instructed to sit and read a selected passage from a psychology textbook for 5 min., the same amount of time allotted for the other groups to consume their food.
The Post-Treatment Trial: Immediately following treatment, subjects’ pain and tactile sensitivity were assessed again by exposing them to the contact heat, followed by the monofilaments. After the experimental phase was complete, subjects in the treatment groups were asked to rate the palatability of the treatment food that they had consumed using a 10-point VAS (endpoints labelled “Strongly Like” and “Strongly Dislike”). This rating was obtained after the pain assessment rather than immediately after ingestion (i.e., before the pain assessment) in attempts to prevent Ss from guessing the experiment’s hypothesis. Finally, all subjects completed a personal questionnaire intended to provide information about each subject’s recent experience with factors known to modulate pain responsivity (e.g., phase of menstrual cycle, smoking, use of oral contraceptives) [
To determine whether there were any relationships between the latency pain measures (threshold and tolerance), or between the VAS pain measures (intensity and unpleasantness), Pearson product-moment correlations were conducted across all participants. As expected, VAS ratings of pain intensity and unpleasantness were highly correlated at pre-treatment (r = 0.40, p < 0.01) as were latency measures of pain threshold and tolerance (r = 0.75, p < 0.001).
One-way ANOVAs revealed no significant differences among the four groups for pre-treatment pain thresholds, pain tolerances, VAS ratings of intensity and unpleasantness, or tactile thresholds (all ps > 0.05).
One-way analyses of covariance (ANCOVAs) comparing the groups at post-treatment (with pre-treatment trial scores serving as the covariate) were performed on each of the four pain measures and on tactile thresholds. The analyses revealed that the groups differed on measures of pain tolerance [F(3,35) = 4.71, p = 0.007] and unpleasantness [F(3,35) = 2.98, p = 0.044]. Post-hoc comparisons showed that the main effect on tolerance was accounted for by a difference between the Palatable sweet group and the Unpalatable group (Newman-Keuls, p < 0.05).
These results lend some support for the existence of SIA in human adult females. Relative to consuming an unpalatable food, consuming a palatable sweet food produced increased pain tolerance. Although the pain tolerance of the palatable and unpalatable groups did not differ significantly from the comparison groups (neutral and nothing), the respective rank order of the four pain tolerance scores was as consistent with the prediction that palatability is a critical factor (i.e., highest ranking for the Palatable group, lowest for the Unpalatable group, with both the Neutral and Nothing groups falling in between). Collectively, these findings confirm the hypothesis that the palatability of the ingested food is important for modifying pain perception. Further support for the role of palatability is provided by several other findings. First, we found significant positive correlations between palatability ratings and the changes from pre- to post-treatment in both pain tolerance (r = 0.47, p < 0.01) and pain threshold (r = 0.36, p < 0.05). Second, as we reported previously [
To confirm that subjects were pre-assigned to the correct treatment groups (i.e., to ensure that those in the Palatable Group, considered the chocolate chip cookies palatable), following ingestion, subjects were asked to rate the food, using a 10-point VAS (endpoints labelled “Strongly Like” and “Strongly Dislike”). Following consumption, the mean VAS palatability ratings for each of the treatment foods were 8.70 (S.E.M. = 0.36, range = 7 - 10) for the cookies, 5.80 (S.E.M. = 1.80, range = 2 - 8) for the rice cakes, and 1.10 (S.E.M. = 0.10, range = 1 - 2) for the black olives. A one-way ANOVA performed on the palatability ratings showed a significant Group effect [F(2,27) = 97.83, p < 0.0001], with each treatment group differing from all other groups (Newman-Keuls. p < 0.05). It is important also to note that the mean ratings of the different ingesta were virtually unchanged from those obtained at the outset of the experiment.
To determine whether there were any relationships between either of the four pain measures and any of the recorded subject variables (e.g., age, stage of menstrual cycle, body weight, use of alcohol, cigarettes, illicit drugs, birth control pills and other medications, amount of sexual activity, exercise, sleep, and food/sweet consumption), multiple Pearson product-moment correlations were conducted. There were no significant correlations between the pain measures and any of the subject variables (all ps > 0.05), suggesting that any pre-existing subject conditions had little, if any, effect upon the results.
EXPERIMENT 2
Experiment 1 showed that the contact-heat method is a suitable method for assessing SIA in adults, at least in women. Therefore, in an attempt to replicate and extend these findings, the present experiment again used the contact-heat method to assess the effects of sweet intake and palatability on analgesia, but this time with a greater number of subjects that included both males and females. Moreover, to examine further the role of palatability, and to maximize the possibility that subjects were experiencing the hedonic value of the palatable food, participants were allowed to consume as much of the experimental food as they desired.
Eighty (40 female and 40 male) right-handed, non-smoking, pain-free Caucasian university students served as subjects (M age = 21.9 years old; range = 18 - 43 years old). An additional 2 subjects were tested but not included in the final sample; 1 female because it was later discovered that she did not meet the experiment’s criteria (i.e., she was not appropriately food-deprived), and 1 male because he kept his forearm on the hot-plate at pre-treatment for the maximum temperature of 48.0˚C (i.e., he showed maximum tolerance).
This study used the same procedure as that of Experiment 1 with the following three exceptions. First, both males and females were tested. Second, before receiving a treatment food, the groups were matched according to their pre-treatment pain tolerance score. This was achieved by calculating for pre-treatment tolerance, a running group mean, including the subject currently being tested. Tolerance was chosen as the matching variable because it was the most sensitive measure both in Exp.1 as well as in previous reports [
As in Expt. 1, intensity and unpleasantness measures were highly correlated at pre-treatment (r = 0.67, p < 0.001 as were measures of threshold and tolerance (r = 0.67, p < 0.001).
As also reported in the previous experiment, one-way ANOVAs revealed no significant differences among the four groups at pre-treatment for pain threshold, pain tolerance, or intensity and unpleasantness VAS ratings (all ps > 0.05).
Consistent with previous findings [
For both men and women, one-way ANCOVAs comparing the Palatable, Unpalatable, Neutral and Nothing groups at post-treatment were performed on each of the 4 pain measures and on tactile thresholds. Women showed group differences on measures of pain threshold [F(3,34) = 4.36, p = 0.0106] and pain tolerance [F(3,35) = 5.20, p = 0.0045]. Specifically, post-hoc comparisons showed that the main effect on tolerance was accounted for by women in the Palatable group showing increased pain tolerance compared to women in all other groups (Newman-Keuls, p < 0.05). As in Expt. 1, omega squared values were high (0.23, 0.32) again indicating strong experimental group effects [
For pain threshold however, the main effect was accounted for by a different pattern of results.
As in our previous study with pressure algometry [
ferent from that of palatable foods. Possible explanations for the relative hypoanalgesic effect of unpalatable foods are offered in section 6.3 of the General Discussion.
Collectively, these results implicate the importance of palatability in the analgesic effect of sweet ingesta. Moreover, the consistent finding that women’s (but not men’s) food palatability ratings are positively correlated with changes (from pre- to post-treatment) in pain tolerance (r = 0.41, p < 0.01) and in pain threshold (r = 0.50, p < 0.005), also indicates that food palatability plays a critical role in the production of analgesia.
As in Expt. 1, to confirm that subjects were pre-assigned to the correct treatment groups, following ingestion, subjects were asked to rate the palatability of the food. The mean VAS palatability ratings for each of the treatment foods were 8.70 (S.E.M. = 0.40, range = 6 - 10) for the palatable cookies, 5.30 (S.E.M. = 0.5, range = 3 - 8) for the neutral rice cakes, and 1.40 (S.E.M. = 0.20, range = 1 - 4) for the unpalatable black olives. A two-way ANOVA [4 (Treatment Group) × 2 (Gender)] performed on the palatability ratings showed a significant group effect [F(2,54) = 168.94, p < 0.0001], with each treatment group differing from all other groups (Newman-Keuls. p < 0.05). Males and females did not differ on overall food palatability ratings [F(1,54) = 0.51, p = 0.48], nor on individual food ratings [all ps > 0.05]. Moreover, the women’s palatability ratings did not differ between Expts. 1 and 2 (p < 0.05), thus showing that eating “as much as they wanted”, did not affect palatability ratings.
Again, to determine whether there were any relationships between either of the four pain measures and any of the recorded subject variables (e.g., age, stage of menstrual cycle, body weight, use of alcohol, cigarettes, illicit drugs, birth control pills and other medications, amount of sexual activity, exercise, sleep, and food/sweet consumption), multiple Pearson product-moment correlations were conducted. There were no significant correlations between the pain measures and any of the subject variables (all ps > 0.05), suggesting that any pre-existing subject conditions had little, if any, effect upon the results.
The present results provide two new significant findings. First, compared to previous pain induction methods such as cold pressor and pressure algometry, contact heat appears to be a superior method for assessing SIA in human adults. Contact heat data also shares the advantage of being more comparable to those obtained from previous well-controlled SIA studies with animals [
The present study was the first to demonstrate that contact heat is a promising method for assessing the presence of SIA in human adults. In two separate experiments, women who consumed a highly rated sweet food (chocolate chip cookies) kept their forearm on a hot-plate longer than women who consumed either non-sweet foods (Expt 1 & 2) or nothing (Expt 2 only). Our results also suggest that contact heat may be a better method of experimental pain induction than those used previously (pressure algometry or CPT) as it does not appear to produce the ceiling effects that can mask the analgesic outcome of sweet ingestion. In the present study, fewer than 2% of the participants kept their arm on the hot-plate as it reached the maximum temperature, compared to 33% of those who left a finger in the pressure algometer at maximum pressure [
Concerning specific measures of pain, our studies of ingestion analgesia [present study; 6,7] consistently demonstrate that pain tolerance is the only index that reliably demonstrates the analgesic effect of sweet ingesta. Whether evaluating pain responsivity to contact heat, pressure, or cold water, threshold measures have shown inconsistent patterns, and intensity and unpleasantness VAS ratings have shown very mixed results (either no change or an increase in pain ratings―effects opposite to those expected for analgesia). It is possible that VAS ratings of unpleasantness and intensity are more suitable for assessing pain in clinical settings rather than for evaluations of experimental pain. Alternatively, VAS ratings may be preferable for evaluating tonic, rather than phasic, pain [
The present finding of a modest effect of SIA in human adults is consistent with suggestions that SIA may disappear, or at least diminish, in adulthood [
Anseloni and colleagues [
The diminishing or the altering of human SIA with age appears to have a different course of development for males compared to females; specifically, it may disappear altogether in males. These developmental gender differences in pain sensitivity are likely due to both biological and psychosocial differences between males and females [
The finding that SIA exists in adult women, but not men, does however conflict with those of other researchers [
Finally, perhaps the most salient reason for the discrepant findings may be due to the interpretation of the results. Based on changes in pain threshold, but not pain tolerance, Kakeda and Ishikawa [
The present study purposively manipulated the palatability of the ingesta in order to determine if palatability is a critical factor in the occurrence of analgesia, or whether the effect is due to sweetness alone, as the terminology “sweet-induced analgesia” has traditionally implied. Results from the present contact heat study, as well as those from our pressure algometry studies [
This palatability explanation is supported by studies with rats and children. First, in a series of very well controlled experiments with rats, Foo and Mason [
Collectively, these findings demonstrate that palatability may be a critical factor in producing ingestion analgesia. Upon closer inspection of the present results, it appears that the type of ingesta may play a modulatory, rather than strictly analgesic role, in pain perception. The present study reported that the largest and most consistent difference in tolerance occurred between the Palatable and Unpalatable groups. Moreover, the pain threshold of the Unpalatable group was lower than that of the Palatable, Neutral and Nothing groups. It is an interesting possibility that unpalatable foods may decrease opioid activity whereas palatable foods increase opioid activity. Alternatively, unpalatable foods may indirectly affect the opioid system by modulating the activity of another neurotransmitter or neuromodulator involved in both food ingestion and pain modulation, such as the neuropeptide, cholecystokinin (CCK). CCK has been shown to attenuate both eating and morphine analgesia [
In summary, the present results confirm the importance of palatability in producing what has been referred to as “sweet-induced analgesia”. Moreover, the present findings are the first to demonstrate that contact heat is a suitable, if not superior, method for the assessment of ingestion analgesia in human adults, at least among females. Women who ingest palatable food endure contact heat pain for longer durations than women who consume nothing, or foods rated as unpalatable or neutral. Therefore, it appears that ingestion analgesia, or perhaps more accurately, palatability-induced analgesia (PIA), does persist beyond infancy. However, the phenomenon may not be as pronounced in adulthood, as it appears to reduce in intensity, is observable only in women, and is highly dependent upon food palatability. This relative suppression may be explained by a decrease in the hedonic value of food, perhaps due to increased variety and experience, or by developmental changes in our pain and analgesia systems (e.g., either chronically elevated opioid levels and/or a down- regulation of opioid receptors, as a result of greater experience with pain and sweets). It may be that PIA (especially in men) serves little biological advantage for human adults compared to infants in whom PIA may serve as mediator of important behaviours such as mother-infant attachment, appropriate food selection, and/or energy conservation.
This research was supported by Natural Sciences and Engineering Research Council of Canada (NSERC) operating grant (A1221) to M. Holder, and by fellowships from NSERC and the Women’s Association of Memorial University to M. Mercer.
Michele E.Mercer,Mark D.Holder,Russell J.Adams, (2015) The Effects of Palatable Sweet Ingesta on Human Responsivity to Heat Pain. Journal of Behavioral and Brain Science,05,405-419. doi: 10.4236/jbbs.2015.510039