Pain sensitivity increases more in younger runners during an ultra-marathon

Introduction

Research interest has increased regarding ultra-endurance athletes over the past decade but pain-related data for this growing population remains insufficient [1]. Participation in ultra-endurance activities is increasing exponentially. According to statistic.d-u-v.org [2], in the year 2000 there were close to 44,000 combined male and female runners in ultra-marathon events worldwide. In 2018 that increased to a total of almost 300,000 combined male and female ultra-marathon runners. That is a 680% increase in ultra-marathon participants in 18 years.

In just 10 years male and female ultra-endurance runners between 23 and 40 years old have increased from 64,576 runners to 257,882 runners. In runners between 41 and 65 years of age the increase, during that same time period, was from 49,393 to 167,039. That is a 399% increase in younger runners and a similar 338% increase in older runners. See Figure 1.

Figure 1:

Data derived from DUV – ultramarathon statistics in 2018. http://statistik.d-u-v.org.

Despite the increase in both the numbers of ultra-marathon participants as well as the increasing number of older runners, there is very little data on variation in pain resulting from ultra-marathon competition for these growing populations.

Pressure pain threshold (PPT) has been shown to increase with aging [3], [, 4]. A decrease in endogenous pain modulation, previously introduced as descending noxious inhibitory control [5] and now measured in humans as conditioned pain modulation (CPM) has also been seen to occur with aging [6]. Our research group has recently shown that PPT and CPM decrease during an ultra-marathon, thus increasing central and peripheral pain sensitivity [1]. Based on the well-known increase in pro-inflammatory markers during an ultra-endurance event [7], [8], [9] we suggested that the decreased PPT and CPM observed resulted from the effects of these inflammatory markers on nociceptor plasticity during the ultra-marathon competition [1].

Recently the terms “Inflammaging” [10], [11], [12] and “immunosenescence” [13], [14], [15] have been introduced from research on changes in the immune system due to aging. This research has predominantly indicated that there is a progressive chronic inflammatory condition occurring with age that is referred to as inflammaging. A greater amount of research on the adaptive immunity changes occurring with age vs. the innate immunity changes with aging, has been done. This research has revealed that both cellular and humoral immunity decrease with age [15] and is now referred to as immunosenescence.

More recently there has been research indicating that, as with immunosenesence, there is a decreased ability to mount an acute, innate inflammatory response to both infection and tissue damage with aging [16].

Given the known innate inflammatory response of ultra-endurance exercise [1], [7], [8], [9], [17]; the well-established mechanism of hyperalgesia [18], and the known variation in pain sensitivity shown to occur with aging [3], [19], [20], we speculated that there may likely be differences in the pain response during an ultra-endurance event due to aging. To investigate the age variation in pain sensitivity during ultra-endurance activity we measured PPT and CPM before and immediately after an ultra-marathon in two age groups: A younger group of runners ≤ 39 years (younger) and older group of Master athletes ≥ 40 years old (older).

Methods

Results

Population parameters are included in Table 1.

Sample characteristics: age group, pre-post, mean, standard deviation and sample size are presented below in Table 2.

Test of assumptions were done. Box’s M indicates homogeneity of covariance matrices (M=15.339; p=0.202; df=10, 5488) is above the criterion α=0.001 for Box’s M, therefore the assumption of equal variances is satisfied.

Normality tests, i.e. tests of the data distribution, indicated pre and post data relative to age groups all satisfy or violate the normality assumptions based on p<0.05 (violate) and p>0.05 (satisfy) and are presented in Table 3.

There were statistically significant within subjects effects on time – pre/post (F=22.094; p=0.001; df=3, 105; ES=0.387 and for the Time x Age Group Interaction (F=3.921; p=0.011; df=3, 105; ES=0.101). This indicates that the ultramarathon race may have had a statistically significant effect on reducing pain sensitivity in both younger and older cohorts as measured by PPT and CPM.

Tests of between-subjects effects indicates a non-significant mean difference between age groups on PPT and CPM (F=0.161; p=0.691; df=1, 35; ES=0.005).

Paired t-tests indicate a statistically significant mean difference for (PrePPTyounger vs. PostPPTyounger; t=4.670; p=0.001; df=16), and a statistically significant mean difference for (PreCPMyounger vs. PostCPMyounger; t=4.803; p=0.001; df=16), as illustrated in Figure 2.

Figure 2:

PPT and CPM were significantly decreased during both the 50 and 100 mile ultra-marathons in the younger group. *p<0.001.

Paired t-tests indicate a statistically non-significant mean difference for (PrePPT-older vs. PostPPT-older; t=1.611; p=0.124; df=19), and a statistically significant mean difference for (PreCPM-older vs. PostCPM-older; t=2.335; p=0.031; df=19), as illustrated in Figure 3.

Figure 3:

In the older group there were no significant difference pre vs. post PPT (p=0.12) during both the 50 or 100 mile ultra-marathons. Pre vs. post CPM was significantly lower post ultra-marathon. *p=0.031.

Bootstrapped paired samples statistical significance/non-significance rates were consistent with non-bootstrapped paired t-test results presented below in Table 4.

Welch’s t-tests (two-independent sample) indicate a statistically significant mean difference (ΔPPT-younger vs. ΔPPT-older; t=2.494; p=0.018; df=33) on pressure pain threshold and a mean difference approaching significance (ΔCPM-younger vs. ΔCPM-older; t=1.727; p=0.093; df=35) on conditioned pain modulation as illustrated in Figure 4.

Figure 4:

There were near significant differences in the ∆PPT (p=0.018). ∆CPM was not significantly different between the age groups (p=0.093). This illustrates the differences in changes of peripheral pain sensitivity as measured by PPT between age groups.

Discussion

Participation in ultra-endurance events has expanded exponentially during the previous five decades [22]. A large percentage of participants are considered “Master” athletes with ages of 40 years and older [2]. To the best of our knowledge, there is no research focused on pain variation in older ultra-endurance athletes during an ultra-marathon.

Pain sensitivity has been shown to increase during an ultra-marathon [1]. This present study extends those findings by investigating these same changes in different age groups. In this study we have seen that an older group of runners had less decrease in PPT and CPM when compared to the younger group during an ultra-marathon. Our present data suggests that older runners complete an ultra-marathon without the same increased sensitivity to pain as younger runners.

In this present study there is a decrease in PPT and CPM in our younger group of runners during an ultra-marathon (Figure 2). While we saw the same decrease in our older group (Figure 3) that decrease in PPT was not statistically significant (p=0.124), whereas the CPM did significantly decrease (p=0.031).

As revealed with our ΔPPT values the amount of decrease in pain sensitivity was less in our older group (p=0.018) when compared to the younger group as seen in Figure 4. Despite a substantial mean difference in ΔCPM between the young and old groups this difference only approached statistical significance (p=0.093) most likely due to lack of power with n=17 in our younger groups and n=20 in the older group.

The increased sensitivity to pain during an ultra-marathon may result from the effects of the well-documented increases in inflammation shown to occur during the extreme exertion of an ultra-marathon [17], [, 23]. Increased inflammatory biomarkers have been shown to result in increased pain sensitivity [18], [24], [25], [26], [27]. Inflammation has repeatedly been shown to occur during ultra-endurance activities [7], [9], [17].

Inflammation is a fundamental response from the innate immune cells that detect tissue injury [28]. Both the adaptive and innate systems of immunity have been shown to be involved in immunosenescence which is defined as the decreased immune response due to aging [29], [, 30]. It has been shown that there is a decreased lymphocyte function of the acquired immune system with aging [31]. The innate immune system involves the initial line of defense of the body that encompasses the inflammatory response to injury typically including neutrophilia. The observation of neutrophilia during intense running is not new. In 1901, Larrabee observed this in four Boston Marathon runners [32]. He referred to the neutrophils then as the “inflammatory” type of leukocytes. Larrabee concluded that “Violent, prolonged, exhausting work produces leukocytosis [sic]”, referring to neutrophilia [32]. Aging has been shown to result in an ineffective innate immune response mediated primarily by the declining neutrophil response [33]. It has been suggested that the age-related failure of the innate immune system may result in increased risk of secondary infection after infection or physical insult [33]. As with the acquired immune system the efficacy of the innate immune system has also been shown to decrease with aging [34].

One very plausible cause for the decreased change in pain sensitivity seen in the older group in the present study may be the documented variation of the innate immune response as we age. Inflammatory biomarkers were not measured in our subjects during their races so we can only hypothesize that a blunted innate immune response, as reported previously with aging [34], may have resulted in the decreased pain sensitivity that we have observed in our older population of ultra-marathoners.

The investigation of pain in an aging population can be challenging as studies of the effects of aging on the response to pain have been disparate. A review on the effects of age on pain sensitivity in 2012 [35] noted that in the 25 studies on the age-related variations in pain sensitivity reviewed there was a decrease in sensitivity in nine out of those 25 studies; 12 out of the 25 showed an increased sensitivity and the remaining four showed no change in sensitivity. They noted the many different factors that must be considered including the research design and the research population.

In this study our research population is unique. Our research design had no delineation of characteristics for our subjects other than being 18 years or older, no previous cold injury and entered into the ultra-marathon with the intention of completing at least 50 or 100 miles within a defined time period. This suggests that these individuals routinely train to achieve this kind of result by including significant submaximal exercise – most likely running – in their daily schedules. With this assumption we expected our subjects to demonstrate similar systemic inflammatory responses that have previously been shown to occur during an ultra-marathon, including: 90-fold increase in CPK, 23-fold increase in CRP and 121-fold increase in IL-6 [17], all inflammatory biomarkers previously shown to result in hyperalgesia [17], [, 18]. Given these previous findings we were confident that our subjects had, in fact, had a significant inflammatory response to their ultra-marathon run. Likewise we shared that same confidence that our subjects had developed the well-documented hyperalgesia that results from these levels of acute inflammation [18], [24], [25].

Other potential causes for the decreased change in pain sensitivity seen in our older group of runners may have been due to variation in fitness level as well as levels of exertion during the ultra-marathon. Inflammatory biomarkers have indeed been shown to be inversely related to maximal oxygen consumption (VO₂max) in healthy men [36]. A recent meta-analysis has shown that there is an anti-inflammatory effect seen in aging populations that have consistently high levels of physical activity [37]. The inflammatory response to different degrees of ultra-endurance exercise has been investigated comparing these factors between athletes in a full vs. a half Ironman Triathlon [38]. In that study IL-6, an inflammatory biomarker, was essentially the same post-exercise for the full Ironman vs. the Half Ironman (18.9 ± 13.1 pg/mL vs. 18.9 ± 13.7 pg/mL, respectively). Other inflammatory biomarkers varied between the different length events: CRP was lower in the half Ironman whereas TNF was surprising higher in the half Ironman.

Fitness level as measured by VO₂max may also affect pain sensitivity. A decreased central and peripheral pain sensitivity has been seen when comparing endurance athletes with a VO₂max > 60 mL/kg/min to a healthy control group while at rest [39]. In the present study each subject was their own control and there was no statistical difference in the PRE PPT and CPM measurement between the age groups (Figure 3). This suggests that if there was a difference in fitness levels between our age groups this did not manifest in differences in pain sensitivity at least at the start of the race.

Exercise-induced hypoalgesia has been seen to actually increase as exertion level increases as during an incremental exercise test [40]. The focus of this present study is to investigate how the pain response in our different age populations may vary during an ultra-marathon. Despite an ultra-marathon being substantially different than a single bout of incremental exercise it is reasonable to address the possibility that exertion level throughout the race may be the driving factor for alterations in pain sensitivity between our age groups. To approximate the degree of exertion in our age groups we calculated the “Age-Graded Times” for each runner in the 50 mile and 100 mile races. Age-graded times have been developed to standardize race times for gender and age groups. As can be observed in Table 1. the age-graded mile pace was 13:42 in our young group compared to 14:18 in our older group during the 50 miles. During the 100 mile race the younger runners the age-graded mile pace was 14:24 and the older group ran at a very similar 14:49 age-graded mile pace.

One important limitation with these data is of course the limitation inherent in field studies. While there is a sacrifice of laboratory control in these data there is a great advantage in being able to obtain data during the actual extreme stress characteristic to these types of ultra-endurance activities [41]. One example of this was in collecting data often in relatively remote locations during a race. The cold water bath required for our CPM measurement was maintained between 12 °C and 15 °C offering logistical challenges to obtain a constant supply of ice in the hot, humid conditions of Florida. Despite the somewhat higher water temperatures we continued to observe the appropriate increased PPT during our cold water immersion at this somewhat higher water temperature seen in related studies [42]. It has been shown that there is no difference in the CPM data with variation in subjective pain ratings during the CPT [43]. Wewould not proceed with the measurement unless the water temperature was equal to or less than 15 °C.

In conclusion we have shown that during either a 50 mile or 100 mile ultra-marathon our runners 40 years or older exhibited less increase in pain sensitivity compared with the younger runners.