The existing research is mixed in regard to changes in pain sensitivity (i.e., pain threshold) with aging (1,2), but has consistently shown that older adults exhibit dysfunctional central pain modulatory processing compared with younger cohorts (3–6). These dysfunctional pain modulatory processes likely increase the risk for persistent pain in older compared with younger adults. Specifically, studies using dynamic psychophysical tests, such as conditioned pain modulation (4), offset analgesia (7), and exercise-induced hypoalgesia (EIH) (8), show that older adults exhibit deficient capacity for descending pain inhibition. Exercise-induced hypoalgesia is a phenomenon in which pain sensitivity and pain perception to noxious stimulation is temporarily reduced after an acute bout of moderate to vigorous exercise (9). We recently revealed that older adults, in contrast to younger adults, do not experience reduced pressure pain sensitivity after an acute bout of isometric exercise or aerobic exercise (8). Additionally, another EIH study demonstrated that while older adults exhibited EIH after isometric exercise, the pain reduction was smaller in magnitude compared with younger adults (10). Although the mechanisms of EIH are not completely understood, animal and human data suggest involvement of the central nervous system and separate mechanisms than that regulating pain inhibition through conditioned pain modulation (11). Thus, collectively, the research shows that aging is associated with a reduced capacity to activate multiple pain inhibitory mechanisms. Understanding modifiable factors associated with age-related dysfunctional central pain modulatory processing is essential to pain prevention and management strategies for this growing segment of the population.
A growing body of evidence suggests a relationship between central pain modulation and physical activity behavior, with more effective pain modulation associated with greater physical activity (12–15). For example, Umeda et al. (16) revealed that differences in EIH between African Americans and non-Hispanic Whites disappear after controlling for physical activity levels, suggesting that reduced physical activity in African Americans contributed to reduced EIH. Additionally, Naugle and colleagues (13) recently showed that older adults who were more active exhibited greater pain inhibitory capacity on the Conditioned Pain Modulation test and less facilitation of pain on the temporal summation test. However, whether regular physical activity behavior influences older adults’ capacity for pain inhibition after acute exercise remains unknown.
Emerging evidence also suggests that psychological processes may influence the capability for central pain modulation, including EIH. Studies in younger adults show that higher pain catastrophizing is associated with less pain inhibition on the Conditioned Pain Modulation test (17) and after acute isometric exercise (18). Furthermore, Brellenthin and colleagues (19) demonstrated that a negative family environment, negative mood, and greater situational catastrophizing predicted worse EIH outcomes in young adults. No studies have investigated the impact of psychological processes on EIH in older adults.
The objective of this study was twofold. First, the current study examined whether healthy older adults experience EIH after a submaximal isometric handgrip. Based on previous studies, we hypothesized that older adults would not experience significant inhibition of experimental pain after acute exercise. Second, an aim of this study was to examine potential psychological and physical activity predictors of the magnitude of EIH after submaximal isometric exercise in healthy older adult men and women. We hypothesized that older adults who did relatively more moderate to vigorous physical activity (MVPA) per week and reported less pain catastrophizing would experience greater inhibition of pain after isometric exercise.
Participants were 53 healthy adults ranging in age from 60 to 77 (males, 20; females, 33). Table 1 presents the descriptive characteristics of the sample. The racial composition of the sample included 48 whites, 1 Hispanic, and 4 African Americans. Participants were recruited through flyers within the local community. The following criteria excluded individuals from the study: 1) current use of narcotics or any tobacco products, chronic use of analgesics, 2) serious systemic disease or conditions that restricted normal daily activities (e.g., cancer, severe osteoarthritis), 3) cognitive impairment that would interfere with understanding of the study procedures as defined by a score of greater than 7 on the Six-Item Cognitive Impairment Test, 4) uncontrolled hypertension, 5) cardiovascular, metabolic, or pulmonary disease, 6) neurological disease, 7) serious psychiatric conditions (e.g., schizophrenia and bipolar disorder), and 8) chronic pain or any ongoing pain problem (headaches, injury-related pain, etc.). Additionally, participants were instructed to refrain from consuming caffeine or any pain medications before the experimental sessions. Although we excluded participants for current use of narcotics and chronic use of analgesics, we did not restrict use of other medications. Participants reported taking the following medications on the day of testing: 1) heart burn medication: proton-pump inhibitors (n = 3); 2) cholesterol reducing medications: statins (n = 5), antilipemic agent (n = 1), and fibric acid (n = 1); 3) antihypertensive medications: angiotensin II receptor antagonists (n = 6), diuretics (n = 2), beta blocker (n = 1), calcium channel blockers (n = 2), and ace inhibitor and channel blocker (n = 1); 4) hypothyroidism medication: thyroid hormones (n = 7); 5) antidepressant (n = 1); 6) Osteoporosis medication: estrogen modulator (n = 1); 7) anti-inflammatory (n = 1); 8) allergy medicine: antihistamine (n = 2); 9) antibiotics (n = 1). We are unaware of any studies examining the effects of these medications on EIH.
The Indiana University Human Subject Review Board approved this study. This study was part of a larger investigation examining the role of physical activity behavior in endogenous pain modulation in older adults (13). Participants completed a screening/orientation session and three experimental sessions. All sessions were scheduled on separate days and separated by at least 48 h. During the experimental sessions, participants completed several questionnaires and the test of EIH. Additionally, physical activity behavior for one week was assessed with an accelerometer. These assessments are described below.
Screening and Orientation Session
The screening and orientation session lasted approximately 2 h and took place on a different day than the experimental sessions. All participants were given information about the experimental procedures, and reviewed and signed a written informed consent form approved by the Indiana University Institutional Review Board before participation in the study. To determine eligibility, participants completed a health history questionnaire, supplemented by interview, blood pressure, and height and weight measurements. Participants were also administered the Six-item Cognitive Impairment Test to ensure that participants were free of cognitive impairment that may inhibit study participation (20). No participants were excluded after the orientation and training session. Once eligibility was determined, participants completed a quantitative sensory test training session which 1) allowed them to become accustomed to the pain tests and laboratory setting and 2) determined individualized temperatures of the stimuli for the heat test stimulus of the EIH protocol such that participants would experience moderate pain (40–60 on a 0–100 numeric rating scale) during the heat trial. For this purpose, 10-s trains of increasing heat stimuli were applied to the forearm until participants experienced a moderate level of pain (40–60 on a 0–100 visual analogue scale). Once this temperature was determined and after a 15-min break, a 30-s heat pain test was administered to ensure a moderate level of pain was experienced during this trial. The 30-s heat pain test was administered again and with the temperature adjusted if pain levels did not reach a maximum of 40–60 out of 100. Participants also completed an assessment of maximal voluntary contraction (MVC) of handgrip muscles, and were given an accelerometer, instructions on how to wear the device, and a physical activity diary. Specific procedures for these assessments are described below.
MVC of the right hand flexor muscles was determined with a hand dynamometer (Jamar Plus digital hand dynamometer; Patterson Medical). The dynamometer handle was adjusted according to manufacture guidelines for each participant. Participants placed their right arm on a table surface with the elbow at a 90° angle and firmly griped the hand dynamometer. Participants were asked to squeeze the dynamometer as hard as possible for 5 s. This procedure was repeated three times with a 1-min rest between trials. The high score of the three MVC was used to calculate the percent of MVC for the submaximal isometric handgrip that was performed in the test of EIH during the experimental sessions.
Assessment of Physical Activity
All participants were instructed to wear an accelerometer (ActiGraph GT3X+) on the hip to measure physical activity levels. The Actigraph is a small lightweight triaxial accelerometer that is designed to detect triaxial accelerations in the range of 0.05g to 2g. Output from the ActiGraph is in the form of step counts, body positions and activity counts for a specific time period. Data were captured in 1-min epochs, and nonwear time was defined as 60 min of consecutive zero counts. Participants were given the accelerometer and instructions on how to wear it during the screening session. They were instructed to wear the accelerometer for seven consecutive days after the screening session except during sleep, showering/bathing, and swimming. A valid day was defined as having worn the device for more than 10 h. Participants were also provided a physical activity diary in which they recorded the start and finish times each day, as well as the duration and reason for any periods where they took the accelerometer off. Participants received reminders from research staff about wearing the accelerometers.
Activity count cut-points to determine the amount of time a participant spent in sedentary, light, or moderate to vigorous activity were defined as <100 counts per minute (sedentary), 100 to 1951 counts per minute (light physical activity [LPA]), and >1951 counts per minute (moderate to vigorous activity), respectively (21). These cutpoints have been used by other studies to measure physical activity behavior in older adults (22,23). Moderate physical activity and vigorous physical activity were combined into MVPA because very few older adults actually performed vigorous physical activity according to the accelerometer data. MVPA was expressed in minutes per day. National guidelines recommend that MVPA should be accrued in bouts of at least 10 min for potential health benefits (24). Therefore, we calculated total minutes of MVPA per day and MVPA accumulated in bouts ≥ 10 min. Light physical activity and sedentary time were expressed in minutes per day and as a percentage of accelerometer wear time per day. Because LPA and sedentary time are highly related to accelerometer wear time, percentage of wear time in LPA and sedentary time were used in the regression analyses.
Exercise-induced hypoalgesia was assessed during one of the experimental sessions. The EIH procedures tested for changes in pressure and heat pain sensitivity (as described under experimental pain measures) after a 3-min trial of submaximal isometric exercise at 25% of MVC (see Fig. 1). Seven minutes separated the prepain tests and the initiation of the isometric contractions for all participants. This period of rest was included to prevent within-session adaptation, as prior work has shown complete recovery of primary afferent responsiveness after 10 min of no pain stimulation (25). For the isometric contraction, participants placed their right arm on a table surface with the elbow at a 90° angle and firmly griped the hand dynamometer. Participants were asked to squeeze the hand dynamometer at 25% MVC for 3 min. Participants saw the dynamometer read-out and adjusted their effort if necessary. Ratings of perceived exertion using Borg’s 6 to 20 RPE scale (26) and heart rate were assessed every 20 s during the isometric exercise trial. Blood pressure was assessed immediately after the isometric contraction. Then the pressure and heat pain tests were administered again (postpain tests). The pain tests were administered on the nonexercised (left) arm.
Pain test stimuli
Two pain test stimuli were administered consecutively before and after the isometric contraction: pressure pain thresholds (PPT) and a continuous heat pain test. We chose to always administer the PPT first and the heat pain test second because PPT were shorter in duration and elicited a very low level of pain compared with the heat pain test. Thus, the PPT were less likely to influence pain perception on the continuous heat pain test than vice versa (heat pain test and then PPT). The first test stimulus was PPT. A digital, handheld, clinical grade pressure algometer was used for the mechanical procedures (AlgoMed, Medoc Advanced Medical Systems, Durham, NC). The tip of the algometer consisted of a rubber flat 1.0 cm2 probe. The experimenter applied a slow constant rate of pressure (30 kPa·s−1) to the left ventral forearm. Participants were instructed to press a response button when the pressure sensation first became painful, at which the algometer was removed. Pressure pain threshold was defined as the amount of pressure in kilopascals (kPa) at which the participant first reported experiencing pain. Two trials were administered consecutively during each pre- and post-EIH test. These trials were averaged for a single pretest and posttest PPT score.
The second test stimulus was a Continuous Heat Pain test, where focal thermal stimuli (44°C–48.5°C) were administered by a Pelteir-based thermode (TSA-II, Medoc; thermode size: 30 mm × 30 mm) to the forearm. For each 30-s continuous heat pain trial, the thermode was first brought to a neutral temperature (32°C) and then ramped (2.0°C·s−1) to the individualized temperature (44°C–48.5°C) determined during the training session and maintained at that temperature for 30 s. The intensity of the pain produced by the contact thermode was rated continuously using an electronic visual analogue scale. The electronic visual analogue scale consists of a low-friction sliding potentiometer (10 cm travel) with the left endpoint defined as “no pain” and the right endpoint as “intolerable pain.” Additional hash marks in increments of 10 are provided to simulate a 0 to 100 numerical rating scale. Participants were instructed to move the slider in proportion to their perceived pain intensity in real time. The Medoc software records the participants’ pain ratings every 10 to 20 ms. The average pain rating for each 30-s trial was calculated and used as the primary outcome measure for the heat pain test. Two trials were administered consecutively with a 1-min intertrial interval during each pre- and post-EIH test. The pre- and post-EIH test trials were averaged for a single pretest and posttest heat pain score.
Calculation of EIH
A change score was calculated for each test stimulus (EIH-PPT and EIH-Heat) with the following formula: post-EIH trial score − pre-EIH trial score. For the EIH-Heat, a negative change score indicated a reduction in pain after the isometric contraction and thus pain inhibition. For the EIH-PPT, a positive change score indicated an increase in PPT after the isometric contraction and thus pain inhibition.
Pain Catastrophizing Scale
The Pain Catastrophizing Scale (PCS) consists of 13 items rated on a 5-point Likert scale (27). The PCS asks the respondents to reflect upon past painful experiences and to rate the degree to which they experienced negative thoughts or feelings about pain. The PCS measures three dimensions of catastrophizing: rumination, helplessness, and magnification. The highest possible score on the PCS is 52, with prior studies showing a cutoff range of more than 20 to 24 points to be related with clinical relevance (28,29).
Tampa Scale of Kinesiophobia-11
The Tampa Scale of Kinesiophobia-11 (TSK) consists of 11 items used to measure fear of movement or re-injury associated with pain (30). The TSK is a reliable and valid method for determining fear of movement in both clinical and nonclinical populations (31,32). The total TSK score ranges from 11 to 44, with higher scores indicating greater fear of movement due to pain.
As the primary purpose of the study was to determine predictors of EIH, a power analysis using G Power 3.0.10 was used to estimate the sample size needed for predicting the change in R 2 in a multiple linear regression model, when the independent variable of interest was added to the model. With an estimated moderate effect size (f 2 = 0.16) and including two covariates, a sample size of 52 participants would provide power of 0.80 at 0.05.
Descriptive statistics were calculated for age, each psychological questionnaire, thermode test temperature for the 30-s heat trials, MVC, average RPE score during the isometric trial, EIH-Heat score, EIH-PPT score, and average time per day spent in accumulated MVPA and MVPA accumulated in bouts ≥ 10 min (MVPA + 10), LPA and sedentary time, and percentage of accelerometer wear time spent in LPA and sedentary time. Shapiro–Wilk’s test of normality indicated that all the above variables except for the RPE scores, LPA, percentage of wear time in LPA, and percentage of wear time in sedentary time were not normally distributed; thus Mann–Whitney U tests were conducted to determine if these variables differed by sex. Independent t-tests were used to examine sex differences in the normally distributed variables.
One purpose of the study was to evaluate whether older adults exhibited significant pain reduction after isometric exercise. Thus, the pre-PPT, preheat pain scores, post-PPT, and postheat pain scores were first evaluated for normal distribution. The Shapiro–Wilk’s test of normality indicated normal distribution of the heat pain scores and the pre-PPT, but not the post-PPT. Because the skewness (skewness = 1.0 ± 0.33, z = 3.03) and kurtosis (kurtosis = 0.42 ± 0.65, z = 0.65) values for post-PPT were in the acceptable range for normal distribution (33), parametric tests were used to analyze this data. Two (sex) × 2 (trial: pre, post) mixed model ANCOVA were conducted on the heat and pressure pain data to determine whether older men and women experienced EIH. Target force level was added as a covariate. Effect sizes were also calculated to determine the magnitude of pain reduction after exercise. Effect sizes were calculated for men and women separately and the sample as a whole. Cohen’s d was defined as the posttest mean minus the pretest mean, divided by the pooled within group standard deviation (d = [X posttest − X pretest]/pooled standard deviation). Reductions in pain after exercise are reflected by positive effect sizes.
Second, Spearman’s rho bivariate correlation analyses were conducted to determine whether EIH was associated with demographic variables, test variables (RPE during isometric exercise, target force production), psychological variables, and physical activity variables. Third, separate hierarchical regressions were conducted to determine significant predictors of EIH-PPT and EIH-Heat. For each regression, age and pretest scores were entered as covariates in the first step. Age was added as a covariate due to prior research showing age associations for EIH. The pretest scores were added as covariates because the pretest PPT score was significantly correlated with EIH-PPT and the pretest heat score was significantly correlated with EIH-Heat. The physical activity variable (MVPA, MVPA + 10, percentage of time in LPA, or percentage of time in sedentary time) was entered on the second step for each regression. Separate regressions were conducted for each physical activity variable.
Table 1 presents the characteristics of the study sample as well as the means and standard deviations (SD) for all the primary measures of the study. The means are separated by sex. Target force production (P < 0.001), sedentary time per day (P = 0.04), and percentage of wear time in LPA (P = 0.019) were the only variables significantly different between sexes.
Changes in pain sensitivity and ratings after isometric exercise
Data are presented as means ± SD. For the PPT, the mixed model ANOVA revealed a significant main effect of trial (F(1,50) = 5.0, P = 0.030) and sex (F(1,50) = 3.2, P = 0.002). Males (M = 424.97 kPa ± 144.7) exhibited greater PPT compared to females (M = 280.42 kPa ± 134.8). Additionally, PPT decreased after the isometric exercise (Trial 1 = 367.18 kPa ± 131.8; Trial 2 = 338.21 kPa ± 134.0; d = −0.31). The effect size for men was larger (d = −.52) than the effect size for women (d = −0.01), indicating that the magnitude of pain facilitation after exercise was greater for men. However, the interaction of sex and trial was not significant, F(1,50) = 2.8, P = 0.098. Figure 2 shows the average PPT for the trials preexercise and postexercise.
No significant differences were found for the suprathreshold heat pain ratings [main effect of time: F(1,50) = 1.6, P = 0.206, d = 0.27; main effect of sex: F(1,50) = 0.28, P = 0.601; time–sex interaction: (1,50) = 1.43, P = 0.24]. Figure 2 shows the average heat pain ratings for the trials preexercise and postexercise. The effect size for men was d = 0.15 and for women d = 0.36.
Correlations between EIH, demographic and test-related variables, and physical activity and psychological variables
Table 2 presents the correlations between EIH-PPT, EIH-Heat, age, body mass index (BMI), target force level, RPE during exercise, MVPA, MVPA + 10, percentage of accelerometer wear time spent in LPA and sedentary time, PCS scores, and TSK scores. EIH-PPT was positively and significantly related to MVPA per day (P = 0.022), but not MVPA + 10. Higher levels of MVPA were associated with greater EIH-PPT. Moderate to vigorous physical activity was also significantly and negatively associated with BMI (P = 0.001), percentage of wear time spent in sedentary time (P = 0.011), and TSK score (P = 0.021). Therefore, those who had higher levels of MVPA also had lower BMI, less sedentary time, and lower fear of pain due to movement. MVPA + 10 was negatively associated with BMI (P = 0.001). Percentage of time spent in sedentary time was also positively associated with TSK (P = 0.001) and BMI (P = 0.008), and negatively associated with percentage of time spent in LPA (P = 0.001).
Predictors of EIH
Table 3 presents the results of the regressions involving MVPA and MVPA+ to predict EIH. The model for prediction of EIH-PPT by MVPA was significant. After controlling for preexercise PPT and age, MVPA significantly predicted the magnitude of EIH-PPT. Participants who averaged greater MVPA per day experienced greater EIH, accounting for 11% of the variance. The model for prediction of EIH-PPT by MVPA + 10 was also significant; however, the only significant predictor was PPT preexercise score. The models involving the prediction of EIH-PPT by percentage of wear time in LPA (P = 0.076) and sedentary time (P = 0.126) were not significant.
The model for prediction of EIH-Heat by MVPA was also significant. However, only preexercise heat pain rating predicted EIH-Heat. The same results were found for MVPA + 10 as a predictor of EIH-Heat. The model for prediction of EIH-Heat by percentage of wear time in LPA was significant (P = 0.008); however, this was driven by the significant effect of pretest heat pain score (age: β = 0.24, P = 0.065; pretest heat pain score: β = −0.37, P = 0.005; LPA: β = 0.09, P = 0.461). Similarly, the model for prediction of EIH-Heat by percentage of wear time in sedentary time was significant (P = 0.09), with the only significant predictor being pretest heat pain score (age: β = 0.24, P = 0.065; pretest heat pain score: β = −0.37, P = 0.005; sedentary time: β = −0.06, P = 0.620).
The primary aims of the present study were to examine the relationship between physical activity levels and psychological variables with EIH in older adults. The results showed that, in general, older adults did not exhibit EIH after submaximal isometric exercise. However, those who accumulated more MVPA per week experienced greater EIH. These results point to potential benefits of physical activity in maintaining EIH capabilities with age.
Supporting previous research, the present study showed that older adults did not exhibit EIH after isometric exercise regardless of test stimulus (8). Exercise-induced hypoalgesia is a common phenomenon seen in younger adults but not consistently present in older adults or those with chronic pain (8,9). Within the present study, older adults failed to show significant heat pain reduction after isometric exercise. Furthermore, participants actually showed a decrease in PPT after exercise. However, the effect sizes suggest that this pain facilitatory effect of exercise was driven by the males, while females showed no change in PPT after exercise. Prior research has shown a minimal to small magnitude of pressure pain reduction after isometric exercise in older adults that was significantly smaller in magnitude compared to younger adults (8,10). For example, Lemley and colleagues (10) found a small pain reducing effect of an isometric contraction of 25% MVC that was held until task failure in older adults. Thus, the EIH effect could be stronger in older adults with isometric exercise of longer duration or greater intensity. Additionally, Naugle et al. (8) found small EIH effects in older adults after isometric exercise and moderate and vigorous aerobic exercise; however, these effects were smaller than the effects of quiet rest. Conversely, Vaegter and colleagues (34) did not find age differences in EIH after isometric or aerobic exercise; however, all participants were under the age of 65 yr. Less research has examined EIH in older adults using heat stimuli, with mixed results (8). Nonetheless, the collective evidence to date suggests a diminished capacity for EIH in pain-free, generally healthy older adults.
As hypothesized, the amount of MVPA per day but not LPA or sedentary time for older adults predicted their level of EIH experienced after isometric exercise. However, MVPA only accounted for 11% of the total variance in EIH. Greater accumulated MVPA corresponded with a greater magnitude of EIH in older adults. Interestingly, only accumulated MVPA per day and not MVPA accumulated in at least 10-min bouts significantly predicted EIH, suggesting that all bouts of MVPA are potentially important in maintaining function of this pain inhibitory system. Along these lines, Umeda et al. (16) found lifestyle physical activity levels influenced EIH differences between African American and non-Hispanic White young adults, such that reduced lifestyle physical activity explained less efficient EIH in African Americans compared to non-Hispanic Whites. In contrast to Umeda et al. and the current study, Black and colleagues (35) found no difference in EIH responses due to physical activity level or type in a group of college-age women. The authors of this study point to two possible reasons for the lack of association between EIH and physical activity: 1) the insufficiently active group still did at least 13 min of vigorous physical activity per day and 2) the impact of physical activity on pain modulation may be greater in older adults, given the decline in physical activity and endogenous pain modulatory function with age. Research has also shown a relationship between physical activity levels and other tests of central pain modulatory processing in older adults. Naugle et al. (10) recently revealed that accumulated MVPA predicted temporal summation of pain (a test of endogenous pain facilitation), while LPA predicted conditioned pain modulation (a test of endogenous pain inhibition). Overall, accumulating evidence supports the notion that physical activity helps to improve central pain-processing mechanisms, particularly in older adults.
Notably, the relationship between EIH and physical activity was observed with PPT as the test stimulus and not the prolonged heat test stimulus. Prior research shows that EIH is partially a function of the experimental pain test (8,18), illustrating the complexity of the EIH phenomenon. Collectively, research on the mechanisms of EIH suggests this phenomenon may be produced by multiple analgesic systems (36,37), each of which may preferentially alter different types of nociceptive input. Future research needs to determine which pain test stimuli during the EIH protocol provide the most clinical significance.
Several potential mechanisms could exist through which regular MVPA enhances the ability to inhibit pain after acute exercise in older adults. First, a common mechanism used to explain EIH involves the activation of endogenous opioid system during exercise. Animal studies show that moderate to vigorous intensity exercise of sufficient duration decreases pain sensitivity in rodents likely through exercise-induced release of central and peripheral beta-endorphins (36,38,39). Additionally, a recent human study suggested, by genetic association, that opioid and serotonergic mechanisms jointly regulated central pain inhibitory signaling after isometric exercise (40). Rodent studies also suggest that aging is associated with decreased opioid peptides and opioid peptide receptor levels in the brain (41), which could contribute to a reduced capacity for EIH in older adults. Notably, regular aerobic exercise in rodents increases endogenous opioid content or release in the brain (42,43). Thus, regular aerobic exercise could prevent or slow the age-related decline in opioid peptides and receptors in the central nervous system, and consequently help older adults maintain the ability to inhibit pain after acute exercise. This opioid-related explanation is clearly speculative and needs further support from animal and human mechanistic studies. Furthermore, a recent human study showed that the administration of an opioid antagonist does not influence the EIH response after isometric exercise, suggesting the involvement of a nonopioid mechanism (37). Another potential mechanism involves alterations of endocannabinoids with age and physical activity. Recently, another human EIH study evaluating isometric exercise suggested involvement of a nonopioid versus opioid mechanism (37,44). Crombie and colleagues (44) discovered that endocannabinoid 2-arachidonoylglycerol concentrations were significantly elevated by isometric exercise and likely played a role in producing EIH. Interestingly, animal studies show that aging is associated with decreased 2-arachidonoylglycerol in the brain (45,46). However, few studies have examined the effects of chronic exercise on levels of endocannabinoids, providing conflicting results (47,48).
The current study did not find relationships between EIH and the psychological variables of pain catastrophizing and fear of movement due to pain. These findings are in contrast to previous research showing relationships between psychological variables and EIH after isometric exercise in younger adults (18,19). For example, Naugle and colleagues (18) revealed that greater pain catastrophizing was associated with smaller reductions in pain after isometric exercise. Furthermore, Brellenthin et al. (19) demonstrated that situational pain catastrophizing predicted magnitude of isometric EIH in younger adults. However, in both of the aforementioned studies, a significant relationship between EIH and pain catastrophizing was specific to the use of temporal summation of pain (i.e., repetitive heat pulses) as the test stimulus during the EIH protocol. Thus, it is possible that a relationship between EIH and pain catastrophizing could exist in older adults with repetitive heat pulses used as the test stimulus. Although fear of pain due to movement was not related to EIH, this variable was negatively associated with MVPA. Thus, older adults who had greater fear of pain also did less MVPA per day. Notably, the participants in our study had low levels of pain catastrophizing and fear of pain. It is possible that those with clinically relevant levels of pain catastrophizing and/or fear of pain may show a different relationship between EIH and these psychological variables.
A few limitations of this study should be noted. First, the present study is cross-sectional which prevents us from being able to show the direction of causality. Without following participants over an extended period of time, it is not possible to conclude whether enhanced EIH is caused by a greater level of MVPA or whether the greater EIH allows for greater amounts of MVPA. Although the relationship is likely somewhat bidirectional, large longitudinal studies suggest that regular exercise can be protective against the development of chronic pain with aging (49–51). Furthermore, recording physical activity for 7 d is a very insightful measure but this is only a tiny portion of participants 60+ yr of activity or inactivity. Third, the older adults in this study were fairly active and healthy; thus, these results may not generalize to older adults with physical disability or chronic pain. Fourth, we did not measure pain during the isometric exercise, which could have varied greatly between participants. Prior research has demonstrated that painful exercise produces greater EIH compared to nonpainful exercise in healthy women, suggesting a possible role of conditioned pain modulation in EIH (11). Finally, the accelerometer data was captured in 1-min epochs. Capturing data in 1-s epochs would have more accurately reflected total MVPA accumulated by participants. Despite these limitations, our data add to the accumulating evidence showing the importance of physical activity for efficient central pain modulatory processing, particularly in older adults. This may be one mechanism through which physical activity may reduce the risk for chronic pain in older adults. Future research needs to determine whether increasing physical activity can prevent the age-related decline in central pain modulatory processing or even “normalize” deficient central pain modulatory processing in older adults.
This research was supported by the IUPUI School of Physical Education and Tourism Management Faculty Research Opportunity Grant.
There are not actual or potential conflicts of interest for any of the authors. The results of this study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation, and the results of the present study do not constitute endorsement by ACSM.
1. El Tumi H, Johnson MI, Dantas PBF, Maynard MJ, Tashani OA. Age-related changes in pain sensitivity in healthy humans: a systematic review with meta-analysis. Eur J Pain
2. Lautenbacher S, Peters JH, Heesen M, Scheel J, Kunz M. Age changes in pain perception: a systematic-review and meta-analysis of age effects on pain and tolerance thresholds. Neurosci Biobehav Rev
3. Edwards RR, Fillingim RB. Effects of age on temporal summation and habituation of thermal pain: clinical relevance in healthy older and younger adults. J Pain
4. 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
5. Naugle KM, Cruz-Almeida Y, Fillingim RB, Staud R, Riley JL 3rd. Novel method for assessing age-related differences in the temporal summation of pain. J Pain Res
6. Naugle KM, Cruz-Almeida Y, Vierck C, Mauderli A, Riley JL 3rd. Age-related differences in conditioned pain modulation of sensitizing and desensitizing trends during response dependent stimulation. Behav Brain Res
7. Naugle KM, Cruz-Almeida Y, Fillingim RB, Riley JL 3rd. Offset analgesia is reduced in older adults. Pain
8. Naugle KM, Naugle KE, Riley JL 3rd. Reduced modulation of pain in older adults after isometric and aerobic exercise. J Pain
9. Naugle KM, Fillingim RB, Riley JL 3rd. A meta-analytic review of the hypoalgesic effects of exercise. J Pain
10. Lemley KJ, Drewek B, Hunter SK, Hoeger Bement MK. Pain relief after isometric exercise
is not task-dependent in older men and women. Med Sci Sports Exerc
11. Ellingson LD, Koltyn KF, Kim J, Cook DB. Does exercise induce hypoalgesia through conditioned pain modulation? Psychophysiology
12. Naugle KM, Riley JL 3rd. Self-reported physical activity predicts pain inhibitory and facilitatory function. Med Sci Sports Exerc
13. Naugle KM, Ohlman T, Naugle KE, Riley ZA, Keith NR. Physical activity behavior predicts endogenous pain modulation in older adults. Pain
14. Ellingson LD, Shields MR, Stegner AJ, Cook DB. Physical activity, sustained sedentary behavior and pain modulation in women with fibromyalgia. J Pain
15. Geva N, Defrin R. Enhanced pain modulation among triathletes: a possible explanation for their exceptional capabilities. Pain
16. Umeda M, Lee W, Marino CA, Hilliard SC. Influence of moderate intensity physical activity levels and gender on conditioned pain modulation. J Sports Sci
17. Weissman-Fogel I, Sprecher E, Pud D. Effects of catastrophizing on pain perception and pain modulation. Exp Brain Res
18. Naugle KM, Naugle KE, Fillingim RB, Riley JL 3rd. Isometric exercise
as a test of pain modulation: effects of experimental pain test, psychological variables, and sex. Pain Med
19. Brellenthin AG, Crombie KM, Cook DB, Sehgal N, Koltyn KF. Psychosocial influences on exercise-induced hypoalgesia. Pain Med
20. Callahan CM, Unverzagt FW, Hui SL, Perkins AJ, Hendrie HC. Six-item screener to identify cognitive impairment among potential subjects for clinical research. Med Care
21. Freedson PS, Melanson E, Sirard J. Calibration of the Computer Science and Applications, Inc. accelerometer. Med Sci Sports Exerc
22. Bann D, Hire D, Manini T, et al. Light intensity physical activity and sedentary behavior in relation to body mass index and grip strength in older adults: cross-sectional findings from the Lifestyle Interventions and Independence for Elders (LIFE) study. PLoS One
23. Cain KL, Millstein RA, Sallis JF, et al. Contribution of streetscape audits to explanation of physical activity in four age groups based on the microscale audit of pedestrian streetscapes (MAPS). Soc Sci Med.
24. Nelson ME, Rejeski WJ, Blair SN, et al. Physical activity and public health in older adults: recommendation from the American College of Sports Medicine and the American Heart Association. Circulation
25. LaMotte RH, Campbell JN. Comparison of responses of warm and nociceptive C-fiber afferents in monkey with human judgments of thermal pain. J Neurophysiol
26. Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc
27. Sullivan MJ, Bishop SR, Pivik J. The Pain Catastrophizing Scale: development and validation. Psychol Assess
28. Wideman TH, Adams H, Sullivan MJ. A prospective sequential analysis of the fear-avoidance model of pain. Pain
29. Scott W, Wideman TH, Sullivan MJ. Clinically meaningful scores on pain catastrophizing before and after multidisciplinary rehabilitation: a prospective study of individuals with subacute pain after whiplash injury. Clin J Pain
30. Kori S, Miller R, Todd D. Kinesiophobia: a new view of chronic pain behavior. Pain Manag
31. Goubert L, Crombez G, Van Damme S, Vlaeyen JW, Bijttebier P, Roelofs J. Confirmatory factor analysis of the Tampa Scale for Kinesiophobia: invariant two-factor model across low back pain patients and fibromyalgia patients. Clin J Pain
32. Vlaeyen JW, Kole-Snijders AM, Boeren RG, van Eek H. Fear of movement/(re)injury in chronic low back pain and its relation to behavioral performance. Pain
33. Ghasemi A, Zahediasl S. Normality tests for statistical analysis: a guide for non-statisticians. Int J Endocrinol Metab
34. Vaegter HB, Handberg G, Graven-Nielsen T. Similarities between exercise-induced hypoalgesia and conditioned pain modulation in humans. Pain
35. Black CD, Huber JK, Ellingson LD, et al. Exercise-induced hypoalgesia is not influenced by physical activity type and amount. Med Sci Sports Exerc
36. Goldfarb AH, Jamurtas AZ. Beta-endorphin response to exercise. An update. Sports Med
37. Koltyn KF, Brellenthin AG, Cook DB, Sehgal N, Hillard C. Mechanisms of exercise-induced hypoalgesia. J Pain
38. Hoeger Bement M, Sluka KA. Low-intensity exercise reverses chronic muscle pain in the rat in a naloxone-dependent manner. Arch Phys Med Rehabil
39. Stagg NJ, Mata HP, Ibrahim MM, et al. Regular exercise reverses sensory hypersensitivity in a rat neuropathic pain model: role of endogenous opioids. Anesthesiology.
40. Tour J, Lofgren M, Mannerkorpi K, et al. Gene-to-gene interactions regulate endogenous pain modulation in fibromyalgia patients and healthy controls-antagonistic effects between opioid and serotonin-related genes. Pain
41. Morley JE, Flood JF, Silver AJ. Opioid peptides and aging. Ann N Y Acad Sci
42. Hoffman P, Terenius L, Thoren P. Cerebrospinal fluid immunoreactive beta-endorphin concentration is increased by voluntary exercise in the spontaneously hypertensive rat. Regul Pept
43. Kim YJ, Byun JH, Choi IS. Effect of exercise on μ-opioid receptor expression in the rostral ventromedial medulla in neuropathic pain rat model. Ann Rehabil Med
44. Crombie KM, Brellenthin AG, Hillard CJ, Koltyn KF. Endocannabinoid and opioid system interactions in exercise-induced hypoalgesia. Pain Med
45. Piyanova A, Lomazzo E, Bindila L, et al. Age-related changes in the endocannabinoid system in the mouse hippocampus. Mech Ageing Dev.
46. Pascual AC, Gaveglio VL, Giusto NM, Pasquaré SJ. Aging modifies the enzymatic activities involved in 2-arachidonoylglycerol metabolism. Biofactors
47. Fernández-Aranda F, Sauchelli S, Pastor A, et al. Moderate-vigorous physical activity across body mass index in females: moderating effect of endocannabinoids and temperament. PLoS One
48. Gasperi V, Ceci R, Tantimonaco M, et al. The fatty acid amide hydrolase in lymphocytes from sedentary and active subjects. Med Sci Sports Exerc
49. Bruce B, Fries JF, Lubeck DP. Aerobic exercise and its impact on musculoskeletal pain in older adults: a 14 year prospective, longitudinal study. Arthritis Res Ther
50. Landmark T, Romundstad P, Borchgrevink PC, Kaasa S, Dale O. Associations between recreational exercise and chronic pain in the general population: evidence from the HUNT 3 study. Pain
51. Hartvigsen J, Christensen K. Active lifestyle protects against incident low back pain in seniors: a population-based 2-year prospective study of 1387 Danish Twins aged 70-100 years. Spine (Phila Pa 1976)