Authors: Yongkang Zhi, Yu Zhang, Yu Zhang, Ming Zhang, Yazhuo Kong
Categories: Research Paper, ageing, heat, older people, pain, pressure, somatosensory, AcademicSubjects/MED00280, ageing/15
Source: Age and Ageing
Pain sensitivity varies across multimodal somatosensory stimuli that can rely on different conductive fibres, which, when damaged, will lead to neuropathies. However, there is limited research examining the characteristics of perceived pain, particularly as affected by the ageing process, as induced by various somatosensory stimuli that may rely on small or large fibres.
Using heat and pressure stimuli on small and large fibres separately on both younger and older adults, this study examined age-associated changes in pain perception by measuring self-reported pain sensitivity, pain threshold and pain discriminability.
Heat pain threshold was significantly positively correlated with age, but not pressure pain threshold. Pain threshold increased and pain discriminability decreased in response to heat stimuli in the older participants compared with the younger ones.
An age-associated decline in heat pain perception was observed, suggesting an earlier degradation of heat perception. These findings provide new insight into understanding and assessing somatosensory disorders, which can help ageing populations better maintain healthy sensory functioning.
Keywords: pain, somatosensory, heat, pressure, ageing, older people
The somatosensory system, which includes the perceptions of tactile, temperature, pressure, and pain as detected through a wide range of sensory receptors [1], provides us with critical information about our internal and external environments [2]. Pain in particular is a significant alert, warning us of potential problems, damage or dangerous situations [3]. Somatosensory stimuli such as heat, cold and pressure can further arouse our perception of physical pain as their intensity increases [4].
Ageing is a natural process during which human experience declines in their somatosensory systems [5, 6], and a change in pain experience is one typical effect of ageing [7, 8]. Somatosensory declines tend to make individuals more susceptible to injury [2], suggesting age-related decreases in pain sensitivity [9]. Previous studies have shown a sensory threshold increase in older adults [10]. However, few studies have distinguished between the degeneration processes of the different somatosensory types. Furthermore, findings regarding age-related changes in pain perception have been inconsistent due to the use of differing pain induction methods [11], as pain sensitivities vary according to stimulation type (e.g. increasing pressure pain versus unchanged heat pain) [11].
Changes in pain perception due to ageing could be related to different somatosensory sensations. Multimodal somatosensation relies on different types of conductive fibres [12]. Peripheral nerve fibres contain both small and large fibres, both of which detect sensations in the skin and carry their respective signals to the central nervous system [13]. Small fibres (e.g. C, Aδ fibres) respond mainly to external thermal, mechanical, or chemical stimulations [14], while tactile and pressure sensations on the skin are often related to large fibres (e.g. Aβ fibre) [15]. Damage to the fibres can cause neuropathies characterised by positive or negative symptoms related to sensation (e.g. neuropathic pain [16], sensory loss [17–21]). Thermal stimulation and pressure can activate small (Aδ and C) and large (Aβ) fibres separately [15, 22–24]; therefore, these stimuli are often used to detect fibre damage [25].
The effects of age-related changes in pain perception are complicated. Pain is a subjective experience, and a complex sensation [26]. Multiple cognitive and emotional factors are known to modulate an individual’s pain experience [27]. The prevalence of chronic pain is known to increase as ageing advances [26], which means that older adults tend to experience more pain-related issues [28]. Furthermore, past painful experiences can also influence older people’s tolerance of painful situations [28].
Considering the potential associations between ageing and pain experience [29], this study aimed to measure age-associated changes in pain perception, in both small and large fibres, using somatosensory rating (i.e. warmth, pressure), pain threshold (i.e. pain from heat, pain from pressure) and pain discriminability (i.e. high versus low intensity). To invoke the sensation of pain, heat and pressure stimuli were administered at various intensities to both older and younger adults. The intent was to obtain measurements from which to develop consultation guidelines when assessing someone for somatosensory disorders or predicting treatment outcomes.
A priori power analysis demonstrated that a sample size of 12 would allow for detecting an effect size (f = 0.25) with 80% power at an α of 0.05 for the repeated measures with one between-participant (i.e. group) and two within-participant variables (i.e. stimulation and intensity) using G^*^Power Version 3.1, according to the guide proposed by Bartlett (2022) (https://osf.io/zqphw/). Thirty-two healthy young adults recruited from the local universities (16 male, age = 23.63 ± 2.37 years, range = 19–28 years) participated in the younger group, and 30 healthy middle-aged or older adults recruited from the local communities (15 male, age = 54.70 ± 9.70 years, range = 40–72 years) in the older group took part in this study. All research procedures were approved by the local institutional review board. All participants in the current research were instructed to not ingest any alcohol or pain medicine for at least four hours before participating in the experiment. After arriving at the lab, each participant underwent a thorough written and verbal informed consent process. Participants were fully debriefed and compensated for their participation after completing all tasks.
The heat pain stimuli were produced using a Medoc 9-cm^2^ Contact Heat-Evoked Potential Stimulator (Medoc Ltd, Ramat Yishai, Israel). The heat pain threshold (younger 43.02 ± 2.73°C; older 45.72 ± 2.07°C) was conducted first to determine whether the designed stimuli would induce pain sensations of different intensities. The heat pain threshold was assessed by administering the probe five times on the participant’s right foot, 3 cm above the middle toe, with a temperature rise rate of 0.5°C/s. Participants indicated when they first began to feel pain by pressing a button that turned the device off. During the main experiment, 5 s heat stimuli with a temperature rise rate of 40°C/s were applied. Forty-five heat pulses measured participants’ perception of the heat stimuli pain at nine intensity 39°C, 40°C, 41°C, 42°C, 43°C, 44°C, 45°C, 46°C and 47°C for younger adults, and 42°C, 43°C, 44°C, 45°C, 46°C, 47°C, 48°C, 49°C and 50°C for older adults. The inconsistent intensity settings are due to the fact that most younger adults were intolerant of the higher thermal stimulation (i.e. 49°C and above), and some older adults failed to detect their heat perception by lower thermal stimulation (i.e. 41°C and below) or were unable to detect their heat pain threshold using the highest intensity administered to the younger group (i.e. 47°C) in our pilot testing experiment. Participants were asked to report the pain they felt during the brief heat stimuli using a numerical pain rating scale ranging from 0 to 10 (0 = no feeling, 1 = a feeling of warmth, 2 = a feeling of heat, 3 = a feeling of hotness, 4 = beginning to feel pain, 10 = a feeling of pain as bad as it could be) [30]. Values from 4 to 10 gradually increased as the degree of pain also increased.
The pressure stimuli were produced using a MRI-Compatible Foot-Sole Stimulation System [31]. The pressure pain threshold (younger 164.36 ± 45.57 N; older 160.32 ± 35.13 N) was first assessed to determine whether the designed stimuli would induce the pain sensations at different intensities. The pressure pain threshold was determined by administering the probe five times to the sole of the participant’s left foot, 3 cm below the middle toe, with a pressure increase of 12 N/s. Participants indicated the point when they began to feel pain through oral report. Next, 5 s of pressure stimuli were then applied in the main experiment. Participants’ pain perception of the pressure stimuli was measured by participants’ responses to 45 pressure pulses at intensities of 100 N, 120 N, 140N, 160 N, 170 N, 180 N, 210 N, 220 N and 250 N in both groups. Participants were asked to report the pain they experienced during the brief pressure stimuli using a numerical pain rating scale ranging from 0 to 10 (0 = no feeling, 1 = a feeling of being touched, 2 = a moderate feeling of pressure, 3 = a strong feeling of pressure, 4 = beginning to feel pain, 10 = a feeling of pain as bad as it could be). Values from 4 to 10 gradually increased along with the degree of pain.
Upon arriving at the lab, and after providing their informed consent, participants were asked to respond to the Pain Sensitivity Scale (PSQ, e.g. ‘Imagine you burn your tongue on a very hot drink,’ responses rated on a 10-point scale ranging from 1 = no pain to 10 = pain as bad as it could be [32]). Then, the participants completed the two-stage main experiment (Figure 1A). The heat and pressure stimuli were applied separately to participants’ right and left feet. Stage 1 measured participants’ perception of one type of stimuli. After assessing the pain threshold, the pain ratings of the heat stimuli were measured according to participants’ responses to 45 heat pulses at various intensities. The presentation of stimuli and manual response measurements were controlled using E-Prime 3.0 (Psychological Software Tools, Inc., Pittsburgh, PA, USA). In each trial, a white fixation cross was first presented for 1 s, followed by instructions (i.e. ‘Heat stimulation on’), shown for 5 s. Meanwhile, a heat pulse was delivered to the right foot. Instructions were then shown on the screen for 5 s, asking participants to consider the sensation they experienced and report a pain rating for the stimuli using the numerical pain rating scale using a response box located by their right hand. After this, a black background screen appeared for 10 s before the subsequent trial began. Stage 2 measured participants’ perception of the other pain stimulus. After assessing the pressure pain threshold, the pain ratings of the pressure stimuli were also measured using participants’ responses to 45 pressure pulses given at various intensities. The setup of each trial was similar to that in Stage 1 but with the instructions written to reflect the given context (i.e. ‘Pressure stimulation on’). The order of the two measured stimuli stages was counterbalanced across all participants.
Figure 1 Pain perception elicited by multiple somatosensory stimuli. (A) Experimental setup and conditions (created with BioRender.com). (B) Pain rating of younger adults regarding heat and pressure stimuli at various intensities. (C) Correlation between age and pain thresholds. (D) Older adults’ pain ratings for heat and pressure stimuli at various intensities.
We first calculated the mean ratings of the heat and pressure stimuli at each level of intensity (Table 1). We expected that the higher the stimulus intensity, the higher the score (Figure 1B and D). We found that the heat threshold (but not pressure threshold) was positively significantly correlated with age across the two groups (rheat-threshold = 0.45, P < 0.001, Figure 1C; rpressure-threshold = −0.175, P = 0.18), suggesting that heat threshold increases with age. Moreover, younger adults’ heat pain threshold was significantly positively correlated with their pressure pain threshold (r = 0.475, P = 0.009), but there was no similar significant correlation in the older adults group (r = −0.173, P = 0.36). In both the younger and older adult groups, no significant gender difference was seen in the pain ratings for heat or pressure stimuli at all levels of intensity (psyounger ≥ 0.154, psolder ≥ 0.278).
To explore the degeneration of pain perception of different types of noxious stimuli, we compared all the pain assessment dimensions between the younger and older adult groups. Compared to younger adults, older adults reported a higher heat threshold (younger 43.02 ± 2.73°C, older 45.72 ± 2.07°C, t(60) = 4.36, pheat-threshold < 0.001, d = 1.11; Figure 2A). No substantial difference was seen between the two groups’ pressure thresholds (younger 164.36 ± 45.57 N, older 160.32 ± 35.13 N, t(60) = −0.38, ppressure-threshold = 0.704; Figure 2B). This implies a degeneration of heat pain perception as we age. Meanwhile, the pain ratings of heat stimuli with supra-threshold intensities for the older group was significantly lower than those for the younger group (younger 3.92 ± 1.69, older 2.79 ± 1.76*, t*(60) = −2.57, p45°C = 0.013, pBonferroni-corrected = 0. 0.0771 (R Studio 2022.07.1), d = 0.65 for 45°C; younger 5.61 ± 1.90, older 3.72 ± 1.89, t(60) = −3.93, p46°C < 0.001, pBonferroni-corrected = 0.0014, d = 1.00 for 46°C; younger 7.44 ± 1.97, older 4.54 ± 2.02*, t*(60) = −5.72, p47°C < 0.001, pBonferroni-corrected = 0.000006, d = 1.45 for 47°C; Figure 2C). There was no significant difference seen in the ratings of pressure stimuli (ps ≥ 0.173, Figure 2D), and the self-reported pain sensitivity between the younger and older adult groups (i.e. PSQ score; younger 4.59 ± 1.37, older 5.20 ± 1.72, t(60) = 1.54, ppain-sensitivity = 0.128).
Figure 2 Comparison of pain perception between younger and older adults. (A) Significant difference in heat threshold. (B) Non-significant difference in pressure threshold. (C) Pain ratings of heat stimuli across younger and older groups. (D) Pain ratings of pressure stimuli across younger and older groups (^^^^P < 0.01, ^^^^^*^P< 0.001).
As impaired somatosensory discriminability (i.e. tactile discrimination) has often been observed in patients experiencing chronic pain [33], we applied an approach to address pain discriminability (i.e. qualified by the area under the curve [AUC] value, which is an oft-used nonparametric measure of discriminability) as proposed by Zhang et al. (2022) to quantify sensory discriminability between the younger and older adult groups [34]. This approach used a rating design in the framework of Signal Detection Theory to calculate the participant’s ability to distinguish between high-intensity stimulation (i.e. signal) and low-intensity stimulation (i.e. noise). Here, participants report pain by a numerical rating scale. This approach was equivalent to treating every numerical rating (0–10) on the scale as an implicit criterion [34]. To calculate the AUC values, for a given criterion (e.g. 6 on the numerical pain rating scale), ratings greater than or equal to this criterion (i.e. 6–10) in the high-intensity stimulation were hit responses, whereas ratings greater than or equal to this criterion in the low-intensity stimulation were false alarms. The hit rate was obtained by dividing the number of hit responses by the number of total trials in the high-intensity stimulation, and the false alarm rate was defined as the proportion of false alarms in the low-intensity stimulation. A hit rate-false alarm rate pair defined a point on the ROC curve (Figure 3A). The numerical rating scale had 11 integral ratings, so there would be 11 points on the ROC curve, and the AUC value was defined as the area under the ROC curve [34]. We calculated the AUC values for each pair of low-high intensity stimuli sequentially (e.g. 45°C versus 46°C for heat stimulation, 160 N vs. 170 N for pressure stimulation), and compared the AUC values of the pain discrimination index between the younger and older adult groups (Table 2). We found that the mean discriminability of heat stimulation (but not pressure stimulation) was significantly negatively correlated with age among both groups (rheat = −0.53, p < 0.001; rpressure = −0.03, P = 0.82, Figure 3D), suggesting that the discriminability of heat stimulation declines as we age.
Figure 3 Pain discriminability by AUC values across younger and older groups. (A) Schematic diagram describing the calculation of the discriminability index (modified from [34]). (B) Significant difference in pain discriminability at various levels of heat and pressure stimuli. (C) Correlations between pain discriminability and pain threshold. (D) Correlations between age and discriminability of heat stimulation (^^^^P < 0.01).
We found that the AUC values of the older adult group were significantly lower than those of the younger adult group, especially for stimuli with intensity around or above the participants’ pain threshold (e.g. 45°C versus 44°C, 46°C versus 45°C and 47°C versus 46°C; Table 2, Figure 3B), also suggesting a decline in the discriminability of heat stimulation as we age. Meanwhile, the older group’s discriminability of heat stimuli was significantly negatively correlated to their heat pain threshold (rolder = −0.60, P < 0.001; ryounger = 0.03, P = 0.89, Figure 3C), meaning that the higher one’s pain threshold, the worse their discriminability, verifying a potential deterioration of the perception of heat stimulation.
We also observed some unstable changes in the discriminability of pressure stimuli when comparing the intensities around the pressure threshold. The older group showed decreased discriminability in the contrast of 160 N versus 140 N (below their pressure pain threshold), but increased discriminability in the contrast of 170 N vs. 160 N (above their pressure threshold), compared with the younger group (Table 2, Figure 3B); however, P values could not survive multiple comparison corrections. It suggests that the discriminability of pressure may remain relatively stable as we age. However, the discriminability of pressure stimulation was not significantly correlated with participants’ pressure threshold, rolder = 0.15, P = 0.433; ryounger = −0.28, P = 0.148.
This study compared pain perception as induced by different somatosensory modalities in both older and younger adults using pressure and heat stimuli with various intensities. We observed an age-associated decline in heat pain perception. Older adults showed decreased pain sensitivity to heat stimuli, that is, a higher heat threshold, but no significant change in pressure threshold. Older adults also demonstrated a reduced discriminability of heat stimuli compared to younger adults. These findings provide insight into somatosensory degradation and its assessment in older adults, potentially contributing to further individualised rehabilitation therapy.
This study shows that the heat pain threshold in older adults increases compared with that of younger adults, suggesting a degradation of heat pain sensitivity. We found that age appears to have a stronger effect on heat sensation (conducted by Aδ and C fibres) compared with pressure sensation (conducted by Aβ fibres). This threshold can yield immediate information as an indicator of somatosensory functioning [35–37].
Age-related differences in pain sensitivity vary across different stimulus modalities [11]. Heat threshold deviations may be an early indicator of ageing. Pain threshold depends on both noxious peripheral input from superficial tissue and the modulatory processing of the central nervous system [38, 39]. At the peripheral level, multiple stimuli-induced somatosensations activate different fibres in the body, which can explain variations in pain thresholds for different sensations. In the current study, the heat stimulus was conducted by small fibres (i.e. Aδ and C fibres) [22], whereas the pressure stimulus was conducted by large fibres (i.e. Aβ fibres) [15]. Both heat and pressure stimuli activate touch-sensitive afferents, however, heat stimuli activate skin nociception, while pressure stimuli target both skin and deep tissue nociceptors [40]. Age-related decrease in heat pain perception may be related to one’s degeneration of the degree of skin innervation with reference to peripheral small fibres [24]. The observed correlation of pain threshold between heat and pressure in younger adults, but not in older adults, also suggests heat-specific changes in older adults. At the central level, age-related differences in phase synchrony between prefrontal regions and sensory cortices suggested one possibility for accounting for deficits in sensory inhibition in older healthy adults [41]. Meanwhile, increased prevalence or severity of disease in older adults could also be associated with age-related changes in central pain sensitivity [26].
Decreased discrimination of heat stimuli, which appeared to occur in parallel with a pain reduction in our study, further confirms the degradation phenomenon of heat pain perception in older adults. The ability to distinguish between stimuli of different intensities is a predominant function of pain perception, indicating the nervous system’s selective encoding of relevant information [34]. For those suffering from chronic pain, it is beneficial to be able to distinguish between painful and non-painful somatosensations, and different sensory qualities of pain [42]. Heat pain is a complicated sensation, comprising the initial sense of pain, which is sharp and very localised based on Aδ fibres, and then followed by secondary pain, a diffuse burning sensation based on C fibres [43]. Reduced discriminability of heat stimulation may result from reorganisation at the somatosensory cortex level due to peripheral and central ageing [44]. Indeed, impaired perceptual discrimination is often observed in older adults suffering from chronic pain [42].
One limitation of the current study is that the age distribution in older adults group was somewhat discrete, while the age distribution in younger adults group was quite concentrated. The recruitment range in this study was from 40 to 75 years of age, with one male and one female recruited for each 3-year age interval. The older group did in fact include participants who were in middle-adulthood as well as seniors, which does not allow for the generalisation of our results to very old individuals. Nevertheless, our results reveal an apparent ageing-related characteristic of diminishing pain perception of heat stimuli. We recommend that future studies further characterise pain perception using additional somatosensory modalities, and using samples that include more divisions in age groups and larger sample sizes. The second limitation is that the same step did not regularly increase the intensity levels of pressure stimuli due to adjusting stimulation settings to distinguish all measures. Future research should use more appropriate stimulation ranges and intensities to measure pressure perception in more detail.
These findings advance our understanding of age-associated declines in sensorimotor functioning and contribute to better assessing the sensory function of patients with somatosensory disorders (e.g. strokes) as they age. Most importantly, it will benefit consideration when developing and selecting optimal, age-appropriate treatment strategies to decrease patients’ pain, particularly in avoiding improper adoptions of physical therapy (e.g. heat or cold packs, massage).
Yongkang Zhi, CAS Key Laboratory of Behavioral Science, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China.
Yu Zhang, Department of Applied Psychology, School of Humanities and Social Sciences, Beijing Forestry University, Beijing 100083, China.
Yu Zhang, CAS Key Laboratory of Behavioral Science, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China.
Ming Zhang, CAS Key Laboratory of Behavioral Science, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China.
Yazhuo Kong, CAS Key Laboratory of Behavioral Science, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China; Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
None.
This research was supported by the National Key R&D Program of China (2022YFC3601701) and the National Natural Science Foundation of China (32100861, 82030121, and 82072010).
All research procedures were approved by the Institutional Review Board of the Institute of Psychology at the Chinese Academy of Sciences (No. H22139) and were performed following the Helsinki Declaration.