Journal Logo

Article

Age effects on pain thresholds, temporal summation and spatial summation of heat and pressure pain

Lautenbacher, Stefana,*; Kunz, Miriama,b; Strate, Peterb; Nielsen, Jesperc; Arendt-Nielsen, Larsc

Author Information
doi: 10.1016/j.pain.2005.03.025
  • Free

Abstract

1. Introduction

Extensive research on age effects on pain perception has been conducted over the years. Whereas most clinical studies have documented an age-related increase in clinical pain (especially in musculoskeletal pain), experimental data are quite contradictory, suggesting that pain sensitivity increases, decreases or remains unchanged over the individual's life span (for a comprehensive review see Gibson and Helme (2001)). These contradicting results may be explained by methodological differences between studies, like age distribution, size and sex ratios of samples, clinical conditions included and the use of different methods of experimental pain assessment. Particularly, the type of stimulus induction method used appears to be one major source of variability. In most studies a diminished sensitivity for heat pain was found whereas no age-related changes resulted from using electrical current (Gibson and Helme, 2001). Induction of ischemia and pressure stimulation—activating nociception in deeper tissue—even demonstrated enhanced pain sensitivity in the elderly (Edwards and Fillingim, 2001a; Pickering et al., 2002; Woodrow et al., 1972). However, these results are subject to one important limitation, namely that in most studies only a single experimental pain induction method has been used, which does not allow for within-study comparisons (between different pain induction techniques within the same group of subjects). Studies are required that use a multimodal sensory testing approach to comprehensively examine the effect of age on pain sensitivity.

When examining the effect of age on pain sensitivity it is not only of importance to describe age-related differences but also to focus on the mechanisms of action that may underlie these differences. Only a small number of studies have focused on these mechanisms. So far, studies have noted some alterations in peripheral A-delta fiber nociceptive function (Chakour et al., 1996) as well as an age-related deterioration in endogenous pain inhibitory systems (Edwards et al., 2003; Washington et al., 2000). Moreover, it has been shown that elderly subjects exhibit stronger temporal summation to heat pain than younger subjects (Edwards and Fillingim, 2001b; Harkins et al., 1996). Generalizations of these results are limited because they can mainly be based on responses to heat stimuli. Consequently, it remains unclear whether or not these results are exclusively linked to pathways signaling nociception induced by heat.

The present study was conducted to add on the description of age-related changes in pain thresholds and somatosensory thresholds by applying various types of stimulus induction (heat, pressure). Furthermore, we assessed temporal and spatial summation of pain in young and elderly subjects. Temporal summation refers to the enhancement of perceived pain intensity when noxious stimuli are delivered repetitively above a critical rate (Price et al., 1977) and it has been shown to be centrally mediated (Vierck et al., 1997). Spatial summation refers to an increase in pain perception when larger areas of stimulation are used and it is thought to be peripherally (primary receptive field sizes) as well as centrally (higher order receptive field sizes) mediated (Raja et al., 1999). The influence of age on spatial summation has not been investigated so far. It has been shown that temporal and spatial summation are potent mechanisms of pain amplification, which are very difficult to block pharmacologically and might be essential for the development of certain chronic pain conditions (Arendt-Nielsen, 1997).

So far, little is known about the influence of sex on age changes in the perception of experimental pain. Therefore, we considered sex as separate variable in all analyses when age-related differences were investigated.

2. Methods

2.1. Subjects

Twenty young subjects between the ages of 21 and 35 years (mean age 27.1±3.5 years) and 20 elderly subjects between the ages of 63 and 88 years (mean age 71.6±5.9 years) participated in the study. Young subjects were recruited from staff members, whereas the elderly subjects were recruited amongst students of the Senior University at the University of Marburg. Each age group consisted of 10 male and 10 female subjects. Participants were screened to exclude conditions that could affect pain perception and pain report such as diabetes, hypertension, peripheral and central neuropathy, neuropsychological and psychiatric disorders. For that purpose, subjects were examined by a physician focusing especially at the neurological disorders. All subjects were pain-free and none had taken any analgesic or sedative medication for at least 48h prior to the test session. The study protocol was approved by the ethics committee of the medical faculty of the University of Marburg. All subjects were paid for participation and gave written informed consent.

2.2. Apparatus

2.2.1. Stimulators

As an indicator of somatosensory sensitivity to mechanical stimuli, the vibration threshold was assessed by a computerized VIBRA-Tester (Phywe GmbH, Göttingen, Germany) with the probe mounted on a swivel arm and a probe area of 0.71cm2.

Contact heat stimuli were delivered by a Peltier-based stimulator (Medoc TSA-2001; Medoc Ltd, Ramat Yishai, Israel). A thermally conductive paste (Hellige, Germany) was filled in between the exposed parts of the thermode and the skin.

A computer-controlled pneumatic pressure algometer (Aalborg University, Denmark) was used to assess responses to painful mechanical pressure (Graven-Nielsen et al., 2004).

2.2.2. Rating scale

For assessment of temporal and spatial summation, subjects were requested to rate pain sensations by use of numerical rating scales (labeled with verbal anchors from ‘no pain’ (0) to ‘extremely strong pain’ (100)).

2.3. Procedures

Testing was conducted in a quiet room around noon (time of assessment was controlled). All subjects were familiarized with the test procedures. This means that they were trained until they understood all procedures and were able to follow the instructions before testing started.

2.3.1. Somatosensory thresholds

Somatosensory testing involved assessment of cold, warmth and vibration thresholds. All somatosensory thresholds were assessed by use of a method of limits protocol very similar to that used in the study of Lautenbacher et al. (1994). Assessment of the vibration threshold was always first, followed by warmth and cold thresholds.

For assessment of vibration threshold the vibration amplitude was increased from 0μm at a rate of change of 0.2μm/s until the subject felt the vibration and pressed a button (vibration detection threshold). There were three trials. Then, in another three trials (vibration disappearance threshold), the vibration amplitude was decreased at the same rate of change from a clearly supra-threshold value until the sensation disappeared. The vibration frequency was kept constant at 100Hz. The site of stimulation was the volar endphalanx of the left middle finger.

For assessment of warmth and cold thresholds thermode temperature increased or decreased from a baseline of 32°C at a rate of 1°C/s until the subjects felt a first change in temperature and responded by pressing a button. Each time they pressed the button, the temperature returned to baseline temperature, which was held constant until the next trial. There were inter-stimulus intervals with a minimum of 15s between each trial. Five trials of warmth and cold stimulation were presented. The site of stimulation was the left volar forearm, where the contact thermode (3×3cm) was attached.

All somatosensory thresholds were determined as the average of all trials.

2.3.2. Experimental pain

To avoid local sensitization stimuli were applied once to the left (pain thresholds, spatial summation) and once to the right body side (temporal summation).

Heat pain stimuli were applied at two volar sites of each forearm: left forearm—proximal part (LF-PP), left forearm—distal part (LF-DP) and right forearm—proximal part (RF-PP), right forearm—distal part (RF-DP), respectively. Pressure pain stimuli were applied at the volar end-phalanx of the middle and ring finger of the two hands: left middle finger (LMF), left ring finger (LRF) and right middle finger (RMF), right ring finger (RRF), respectively.

2.3.2.1. Pain thresholds and spatial summation

Pain thresholds and spatial summation of supra-threshold ratings (assessed only on the left body side) were determined by applying once a ‘small’ (1cm2 for heat pain and 0.25cm2 for pressure pain) and once a ‘large’ (6cm2 for heat and 0.75cm2 for pressure) probe area. The different stimulus areas were achieved either by interposing an insulating material (plastic, 0.3cm thickness), hollowed in the center, between the contact thermode and the skin (Lautenbacher et al., 2001) for heat pain stimulation or by changing the probe of the stimulator for pressure pain application.

To control for possible order effects, one half of the subjects in each age group was tested according to the sequence: heat pain: 1cm2 at LF-DP, 6cm2 at LF-PP, pressure pain: 0.25cm2 at LMF, 0.75cm2 at LRF whereas the other half was tested according to the sequence: heat pain: 6cm2 at LF-DP, 1cm2 at LF-PP, pressure pain 0.75cm2 at LMF, 0.25cm2 at LRF. For each stimulation area, pain thresholds were assessed first and summation testing second at the same site in one run. We always started with the application of heat pain.

Heat and pressure pain thresholds were measured using the same tracking algorithm (staircase method) as in the study of Nielsen and Arendt-Nielsen (1997). The stimulus intensity was increased in steps of 2°C or 200kPa, respectively, until the first report of ‘pain’, then decreased in steps of 1°C or 100kPa, respectively, until the first report of ‘no pain’, followed by steps of 0.5°C or 50kPa, respectively (higher or lower intensities depending on the subject's report of ‘pain’ or ‘no pain’) until three upward turning points (of the staircase) were reached. The pain thresholds were determined as the median value of these three upward turning points. The heat pain stimuli (saw-tooth shape) started at a baseline temperature of 35°C and increased with a heating rate of 4°C/s. The pressure pain stimuli (saw-tooth shape) started at a baseline of 0kPa and increased with an application rate of 1000kPa/s. As described above, two areas per physical stimulus type were used (small/large), resulting into two threshold values for each stimulus induction method.

Supra-threshold spatial summation was tested using the same procedure as in the study of Lautenbacher et al. (2001). A run of 20 stimuli was applied for the small and large contact area, respectively, for each stimulus induction method. The run of 20 stimuli consisted of five series of four intensities (0–3°C and 0, 100, 200, 300kPa above the individual pain threshold). Within each series, intensities were presented in a random order, which was the same for all areas and all subjects. The heat pain stimuli (saw-tooth shape) started at a baseline temperature of 35°C and increased with a heating rate of 4°C/s. The pressure pain stimuli (saw-tooth shape) started at a baseline of 0kPa and increased with an application rate of 1000kPa/s.

2.3.2.2. Temporal summation

For assessment of temporal summation only one area per physical stimulus type was applied (6cm2 for heat and 0.75cm2 for pressure). Temporal summation was determined by applying a ‘slow’ series with 6.4s inter-stimulus intervals (ISIs) (0.16Hz) and once a ‘fast’ series with 2.4s ISIs (0.42Hz). These ISIs were selected, because previous findings suggest that only ISIs shorter than 3s cause temporal summation, whereas series with ISIs longer than 5s (0.20Hz) do not cause temporal summation (Price et al., 1977). One half of the subjects in each age group was tested according to the sequence: heat pain: 6.4s ISIs at RF-DP, 2.4s ISIs at RF-PP, pressure pain: 6.4s ISIs at RMF, 2.4s ISIs at RRF, whereas the other half was tested according to the sequence: heat pain: 2.4s ISIs at RF-DP, 6.4s ISIs at RF-PP, pressure pain: 2.4s ISIs at RMF, 6.4s ISIs at RRF. Temporal summation was tested by comparing the sensations evoked by single pulses (assessed first) to sensations evoked by trains of 5 pulses (only the last pulse was rated). The stimuli were presented relative to the individual pain thresholds (3°C above for heat and 300kPa above for pressure). The heat pain stimuli (saw-tooth shape) started at a baseline temperature of 2°C below the individuals pain threshold and increased with a heating rate of 4°C/s. The pressure pain stimuli (saw-tooth shape) started at a baseline of 200kPa below the pain threshold and increased with an application rate of 1000kPa/s.

2.4. Statistics

Data were statistically analyzed using SPSS version 11.0 for Windows. All data are given as means±SD. The effects of age and sex on somatosensory thresholds were evaluated using analyses of variance (ANOVA) with two group factors (age/sex). The effects of age and sex on pain thresholds were assessed by analyses of variance with repeated measurements, with two between-subject factors (age/sex) and one within-subject factor (contact area). To evaluate the effects of age and sex on supra-threshold pain ratings both in the spatial and temporal summation paradigms, analyses of variance with repeated measurements were used with two between-subject factors (age/sex) and two within-subject factors (contact area/stimulus intensity for spatial summation and pulse number/ISIs for temporal summation). In case of significant results, t-tests were used for pair-wise comparisons. We mainly focused on results regarding age-related effects but interactions including age and sex are also reported. The value of α for significance was set to 0.05 throughout.

3. Results

3.1. Somatosensory thresholds

All somatosensory thresholds were significantly higher in the elderly (cold: F(1,36)=8.6; P=0.006; warmth: F(1,36)=6.2; P=0.017; vibration: F(1,36)=12.4; P=0.001) (Fig. 1) compared with the younger subjects. ANOVAs revealed no significant interaction effects between ‘age’ and ‘sex’ on somatosensory thresholds (see Table 1). However, women had significantly lower warmth thresholds than men (F(1,36)=5.8; P=0.021).

F1-23
Fig. 1:
Vibration, cold and warmth thresholds (Mean, ±SD), *P<0.05, **P<0.01, ***P<0.001 for differences between age groups.
T1-23
Table 1:
Results of ANOVA for the effect of ‘age’ and ‘sex’ on somatosensory and pain thresholds

3.2. Pain thresholds

There was a significant age effect on pressure pain thresholds (F(1,36)=10.0; P=0.003), with the elderly subjects showing significantly lower thresholds (Fig. 2 and Table 1). For pressure stimulation this age-related decrease reached significance both when using the small area (t-test; t=2.54, P=0.016) and when using the large area of probe (t-test; t=2.58, P=0.017). In contrast, the two age groups did not differ in regard to heat pain thresholds (see Table 1). The effect of ‘contact area’ on pain thresholds was highly significant for pressure pain (F(1;36)=13.8, P=0.001) and close to significance for heat pain (F(1,36)=3.5; P=0.068), with the larger areas leading to a decline in pain thresholds, which suggests spatial summation at pain threshold (Table 1). There were no significant ‘age’ and ‘sex’ interactions on pain thresholds (see Table 1).

F2-23
Fig. 2:
Heat and pressure pain thresholds (Mean, ±SD), *P<0.05 for differences between age groups.

3.3. Supra-threshold spatial summation

No significant age effects on pain ratings for heat and pressure stimuli could be observed with regard to supra-threshold spatial summation. Neither were any of the interactions involving ‘age’ and ‘sex’ significant (see Table 2). The significance of the factor ‘stimulation intensity’ was not surprising; it simply mirrors the fact that stronger stimulation leads to higher pain ratings (see Fig. 3). In contrast to spatial summation in heat pain, where no significant effects of the factor ‘contact area’ could be obtained, there was such an effect regarding pressure pain (Table 2). In the latter case smaller contact areas were apparently associated with lower numerical ratings (see Table 4). Interactions with more than 2 factors (not reported in Table 2) were all not significant.

T2-23
Table 2:
Results of ANOVA for the effect of ‘age’, ‘sex’, ‘area’ and ‘stimulus intensity’ on numerical ratings in the supra-threshold spatial summation paradigm for heat and pressure pain
F3-23
Fig. 3:
Mean numerical ratings of the supra-threshold pain sensations evoked by four different stimulus intensities relative to the pain threshold using two different probe areas (small/large) for heat and pressure stimulation.
T4-23
Table 4:
Mean values (±SD) for numerical ratings for supra-threshold spatial and temporal summation in young and elderly subjects

3.4. Temporal summation

Main effects of ‘age’ on pain ratings for single and repeated heat and pressure stimuli were not significant (Table 3). However, we found a significant interaction effect of ‘age’ and ‘pulse number’ for heat pain, with elderly subjects showing a steeper increase in pain ratings from assessment of a single pulse compared to assessment of the last pulse in a series of 5 pulses (Fig. 4). This interaction suggests increased temporal summation in the elderly subjects. No comparable age-related changes in temporal summation were present for pressure pain.

T3-23
Table 3:
Results of ANOVA for the effect of ”age’, ‘sex’, ‘pulse number’ and ‘ISIs’ (inter-stimulus intervals) on numerical ratings in the temporal summation paradigm for heat and pressure pain
F4-23
Fig. 4:
Mean numerical ratings of heat and pressure pain to stimuli delivered as single pulse and as last pulse in a series of five, using two different ISIs (2.4 s/6.4 s) (intensities are relative to pain threshold), **P<0.01 for differences between age groups regarding temporal summation.

There was a significant main effect for pulse number (single pulse vs. last pulse in a series of 5 pulses) both in heat and in pressure pain (see Table 3), with numerical pain ratings being higher after a series of pulses (see Table 4), thus reflecting temporal summation. This finding was independent of the duration of the inter-stimulus intervals (ISI 2.4s vs. ISI 6.4s). ‘Age’ and ‘sex’ interactions as well as all interactions with more than 2 factors (not reported in Table 3) were not significant.

4. Discussion

The major findings of the present study are: (i) that somatosensory thresholds clearly increase in the elderly; (ii) that pressure pain thresholds appear to decrease whereas heat pain thresholds remain unchanged; (iii) that there are no age-related changes in regard to spatial summation of heat and pressure pain and (iv) that temporal summation of heat pain is markedly increased in elderly individuals whereas temporal summation of pressure pain shows no age effects. We discuss these findings in this order.

4.1. Somatosensory thresholds

In accord with the results of others (Gescheider et al., 1994; Kenshalo, 1986; Lautenbacher and Strian, 1991; Stevens and Choo, 1998; Verrillo et al., 2002) we found a decreased somatosensitivity, i.e. lower warmth, cold and vibration thresholds in the elderly. The age effects appeared to be stronger for vibration (Aβ-fibers) compared to thermal sensitivity (Aδ- and C-fibers) as also known from earlier studies. This age-related decline was suggested to be due to a subclinical distal axonopathy (Schaumburg et al., 1983). However, in a more recent study altered receptor properties were suggested to explain the age-related decline (Meliala et al., 1999). In any case, our results show prototypical age changes in somatosensitivity and suggest representative samples in this respect.

4.2. Pain thresholds

In agreement with preceding studies, we found that the effect of age on pain thresholds is dependent on the type of pain induction. Whereas elderly subjects demonstrated a slightly (but non-significant) diminished heat pain sensitivity, pressure pain sensitivity was markedly enhanced in the elderly as also shown by others (Edwards and Fillingim, 2001a; Pickering et al., 2002; Woodrow et al., 1972). The latter finding is especially noteworthy because it contrasts the aging trend in somatosensitivity.

The finding of almost opposing changes for heat and pressure pain suggests that deep tissue (muscle, fascia and tendon) nociception is affected differently by age than superficial tissue (skin) nociception. To understand this conclusion, it is necessary to consider that heat stimuli selectively activate skin nociception whereas pressure stimuli target both at skin and deep tissue nociceptors with a relative preponderance of the latter ones (Kosek et al., 1999). Previous findings indicate that information from deep tissue nociceptors are processed differently in the spinal cord than that from superficial tissue nociceptors (Wall and Woolf, 1984), with spinal input from deep tissue nociceptors being subject to stronger descending inhibitory control compared to skin nociceptors (Mense, 1993; Yu and Mense, 1990). Recent studies documented an age-related reduction in endogenous pain inhibition (Edwards et al., 2003; Washington et al., 2000). Therefore, if descending inhibition modulates deep tissue pain most efficiently, an age-related decline in endogenous pain inhibition might be more evident for pressure pain than for heat pain. Accordingly, our finding of an age-related enhancement in pressure pain sensitivity is of great interest for the observation that elderly individuals are much more likely to develop musculoskeletal pain than their younger counterparts (Gibson and Helme, 2001) because these pain syndromes are associated both with an increased pressure pain sensitivity and a deficient descending inhibitory control.

An alternative explanation may be that local changes in the skin and muscle, e.g. changes in tissue elasticity and conductivity, occurring with age produce different effects on heat and pressure pain sensitivity. Furthermore, there may be different age-related changes in thermally and mechanically sensitive nociceptive fibers, which occur irrespectively of the tissue the fibers project from.

4.3. Spatial summation

To our knowledge, this is the first time that age effects on spatial summation of heat and pressure pain were investigated. We did not observe age-related changes in spatial summation within the range of probe areas studied. However, we cannot rule out that age-related changes in spatial summation might have been observed using smaller areas than those used in the present study. Smaller areas might be more sensitive to age-related changes in the density of nociceptive fibers, which likely occur given the observed changes in somatosensory thresholds. However, we used those area sizes that have been shown to be crucial in the assessment of spatial summation in earlier studies (Defrin and Urca, 1996; Defrin et al., 2003; Lautenbacher et al., 2001).

Our methodological approach allowed separating effects of spatial summation leading to a shift in pain threshold from those leading to a change in slope of the psychophysical function, i.e. to supra-threshold changes. Both in young and elderly individuals we found evidence for spatial summation, which was close to significance for heat pain and highly significant for pressure pain, when considering pain threshold. Accordingly, spatial summation appeared mainly as a left-ward shift of the whole psychophysical function, which is in agreement with previous findings (Defrin and Urca, 1996; Lautenbacher et al., 2001). There was also a significant but small effect of ‘area’ on supra-threshold ratings when using pressure pain, indicating a small increase in slope of the psychophysical function due to spatial summation whereas no additional summation effect on supra-threshold sensations was observed for heat pain.

4.4. Temporal summation

In accord with two other studies we demonstrated that temporal summation of heat pain is greater in the elderly compared to younger individuals (Edwards and Fillingim, 2001b; Harkins et al., 1996). Since temporal summation is modulated by endogenous pain inhibitory systems (Price et al., 2002), the finding, that endogenous pain inhibition (i.e. DNIC) appeared to be reduced in the elderly (Edwards et al., 2003; Washington et al., 2000), is noteworthy. Thus, the enhanced temporal summation of heat pain in the elderly might be caused by a reduced endogenous pain inhibition in senescence (Edwards and Fillingim, 2001b).

However, we did not find an age-related effect on temporal summation of pressure pain, which is surprising because we observed age-related changes in pressure pain thresholds and hypothesized that the age-related reduction of endogenous pain inhibition affects especially pressure pain sensitivity. According to these considerations, age changes in temporal summation should be ever stronger for pressure than for heat pain. One possible methodological explanation might be that pressure pain triggered a much stronger temporal summation in both age groups (effect size d=1.52) than did heat pain (effect size d=0.77) under the given experimental conditions. It is possible that this very strong temporal summation for pressure pain resulted into a ceiling-effect, which made the detection of different degrees of temporal summation between age groups more difficult.

However, we cannot rule out that other factors might have also played a role in regard to our finding of an age-related enhancement of temporal summation of heat pain but not of pressure pain. For example, poorer tissue perfusion in the elderly (possibly leading to a grater thermal build-up in the skin) might have caused the age-related enhancement of pain ratings only for repeated heat pain stimuli and not for pressure pain stimuli.

Our findings regarding temporal summation deserve some further comments independently from potential age changes. Temporal summation occurred irrespectively of the frequency of stimulus repetition although the frequencies were selected to be either below or slightly above the critical frequency reported by Price et al. (1977). Price et al. (1977) observed that noxious heat pulses applied at frequencies higher than once every 3s (0.33Hz) caused temporal summation whereas lower frequencies (inter-stimulus interval (ISI) of 5s; 0.20Hz) did not. However, other authors reported that temporal summation of heat and pressure pain also occurs with ISIs of 5 or 6s (Lautenbacher et al., 1995; Sarlani and Greenspan, 2002; Taud et al., 2001; Vierck et al., 1997). Accordingly, our present finding of temporal pain summation at ISIs longer than 3s is not new. It is possible that these contradictory results may be due to different stimulus intensities or different sizes of probe. Higher intensities result in increased pain summation as has been reported by Nielsen and Arendt-Nielsen (1998). Small thermode areas (e.g. 1cm2 as used by Price et al. (1977)) may require ISIs shorter than 3s to elicit temporal summation whereas larger thermode areas (6cm2 as used in the present study) may elicit temporal summation even at longer ISIs.

4.5. Sex-related age changes

We did not find any significant interactions between sex and age in somatosensory thresholds or in any of the pain parameters. Therefore, age effects on heat and pressure pain thresholds, temporal summation and spatial summation of heat and pressure pain do not seem to be sex-related.

4.6. Limitations

One limitation of the present study is that the mean age of the older subjects was 71.6 years (with a maximum of 88 years), which does not allow for generalization of our results to very old individuals. Nevertheless, the older population of the present study lies well in the upper age range investigated so far in previous studies. Furthermore, the sample size we used might have been too small to detect some effects, especially in regard to sex-related age effects on pain perception. Riley et al. (1998) suggested a sample size of N=41 per group to guarantee adequate power when looking for sex differences. Thus, our sample size might have been too small to find sex-related age changes. However, our focus of interest was on clinically relevant and robust age differences and not on sex.

In summary, the results of the present study demonstrate that somatosensitivity for non-nociceptive stimuli clearly decreases with age whereas pain perception is subject to stimulus-specific changes, with an increased pressure pain sensitivity and an unchanged heat pain sensitivity in the elderly. Apart from an enhanced temporal summation of heat pain in the elderly, summation mechanisms contribute only moderately to age changes in pain perception. No interaction between sex and age in somato- and pain sensitivity was found.

Acknowledgements

We thank the Deutsche Forschungsgemeinschaft (La 685/5), the Gesellschaft fuer Neurobiologische Forschung und Therapie and the Danish National Research Foundation for support.

References

Arendt-Nielsen L., 1997. Induction and assessment of experimental pain from human skin, muscle, and viscera. In: Jensen TS, Turner JA, Wiesenfeld-Hallin Z, editors., 8th World congress on pain. IASP Press, Seattle, pp. 393-425.
Chakour MC, Gibson SJ, Bradbeer M, Helme RD. The effect of age on A delta- and C-fibre thermal pain perception. Pain. 1996;64:143-152.
Defrin R, Urca G. Spatial summation of heat pain: a reassessment. Pain. 1996;66:23-29.
Defrin R, Ronat A, Ravis A, Peretz C. Spatial summation of pressure pain: effect of body region. Pain. 2003;106:471-480.
Edwards RR, Fillingim RB. Age-associated differences in responses to noxious stimuli. J Gerontol A Biol Sci Med Sci. 2001;56:180-185.
Edwards RR, Fillingim RB. Effects of age on temporal summation and habituation of thermal pain: clinical relevance in healthy older and younger adults. Pain. 2001;2:307-317.
Edwards RR, Fillingim RB, Ness TJ. Age-related differences in endogenous pain modulation: a comparison of diffuse noxious inhibitory controls in healthy older and younger adults. Pain. 2003;101:155-165.
Gescheider GA, Bolanowski SJ, Hall KL, Hoffman KE, Verrillo RT. The effects of aging on information-processing channels in the sense of touch: I. Absolute sensitivity. Somatosens Mot Res. 1994;11:345-357.
Gibson SJ, Helme RD. Age-related differences in pain perception and report. Clin Geriatr Med. 2001;17:433-456.
Graven-Nielsen T, Mense S, Arendt-Nielsen L. Painful and non-painful pressure sensations from human skeletal muscle. Exp Brain Res. 2004;159:273-283.
Harkins SW, Davis MD, Bush FM, Kasberger J. Suppression of first pain and slow temporal summation of second pain in relation to pain. J Gerontol. 1996;51:260-265.
Kenshalo DR. Somesthetic sensitivity in young and elderly humans. J Gerontol. 1986;41:732-742.
Kosek E, Ekholm J, Hansson P. Pressure pain thresholds in different tissues in one body region. The influence of skin sensitivity in pressure algometry. Scand J Rehabil Med. 1999;31:89-93.
Lautenbacher S, Strian F. Similarities in age differences in heat pain perception and thermal sensitivity. Funct Neurol. 1991;6:129-135.
Lautenbacher S, Roscher S, Strian F, Fassbender K, Krumrey K, Krieg JC. Pain perception in depression: relationship to symptomatology and naloxone-sensitive mechanisms. Psychosom Med. 1994;56:345-352.
Lautenbacher S, Roscher S, Strian F. Tonic pain evoked by pulsating heat: temporal summation mechanisms and perceptual qualities. Somatosens Mot Res. 1995;12:59-70.
Lautenbacher S, Nielsen J, Andersen T, Arendt-Nielsen L. Spatial summation of heat pain in males and females. Somatosens Mot Res. 2001;18:101-105.
Meliala A, Gibson SJ, Helme RD., 1999. The effect of stimulation site on detection and pain thresholds in young and older adults. IXth world congress on pain, IASP Press, Seattle, p. 559.
Mense S. Nociception from skeletal muscle in relation to clinical muscle pain. Pain. 1993;54:241-289.
Nielsen J, Arendt-Nielsen L. Spatial summation of heat induced pain within and between dermatomes. Somatosens Mot Res. 1997;14:119-125.
Nielsen J, Arendt-Nielsen L. The importance of stimulus configuration for temporal summation of first and second pain to repeated heat stimuli. Eur J Pain. 1998;2:329-341.
Pickering G, Jourdan D, Eschalier A, Dubray C. Impact of age, gender and cognitive functioning on pain perception. Gerontology. 2002;48:112-118.
Price DD, Hu JW, Dubner R, Graceley RH. Peripheral suppression of first pain and central summation of second pain evoked by noxious heat pulses. Pain. 1977;3:57-68.
Price DD, Staud R, Robinson ME, Mauderli AP, Cannon R, Vierck CJ. Enhanced temporal summation of second pain and its central modulation in fibromyalgia patients. Pain. 2002;99:49-59.
Raja SN, Meyer RA, Ringkamp M, Campbell JN. Peripheral neural mechanisms of nociception. Wall PD, Melzack R, editors. Textbook of pain. 4th ed. Edinburgh: Churchill Livingstone; 1999: pp. 11-57.
Riley JL, Robinson ME, Wise EA, Myers CD, Fillingim RB. Sex differences in the perception of noxious experimental stimuli: a meta-analysis. Pain. 1998;74:181-187.
Sarlani E, Greenspan JD. Gender differences in temporal summation of mechanically evoked pain. Pain. 2002;97:163-169.
Schaumburg HH, Spencer PS, Ochoa J., 1983. The aging human peripheral nervous system. In: Katzman R, Terry R, editors., The neurology of aging. Davis, Philadelphia, pp. 111-122.
Stevens JC, Choo KK. Temperature sensitivity of the body surface over the life span. Somatosens Mot Res. 1998;15:13-28.
Taud R, Vierck CJ, Cannon RL, Mauderli AP, Price DD. Abnormal sensitization and temporal summation of second pain (wind-up) in patients with fibromyalgia syndrome. Pain. 2001;91:165-175.
Verrillo RT, Bolanowski SJ, Gescheider GA. Effect of aging on the subjective magnitude of vibration. Somatosens Mot Res. 2002;19:238-244.
Vierck CJ Jr, Cannon RL, Fry G, Maixner W, Whitsel BL. Characteristics of temporal summation of second pain sensations elicited by brief contact of glabrous skin by a preheated thermode. J Neurophysiol. 1997;78:992-1002.
Wall PD, Woolf CJ. Muscle but not cutaneous C-afferent input produces prolonged increases in the excitability of the flexion reflex in the rat. J Physiol. 1984;356:443-458.
Washington LL, Gibson SJ, Helme RD. Age-related differences in the endogenous analgesic response to repeated cold water immersion in human volunteers. Pain. 2000;89:89-96.
Woodrow KM, Friedmann GD, Siegelaub AB. Pain tolerance: differences according to age, sex and race. Psychosom Med. 1972;34:548-556.
Yu XM, Mense S. Response properties and descending control of rat dorsal horn neurons with deep receptive fields. Neuroscience. 1990;39:823-831.
Keywords:

Age; Heat pain; Pressure pain; Temporal summation; Spatial summation; Experimental pain

© 2005 Lippincott Williams & Wilkins, Inc.