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Research Paper

Physical activity behavior predicts endogenous pain modulation in older adults

Naugle, Kelly M.a,*; Ohlman, Thomasa; Naugle, Keith E.a; Riley, Zachary A.a; Keith, NiCole R.a,b

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doi: 10.1097/j.pain.0000000000000769
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1. Introduction

The experience of pain depends on complex interactions between ascending peripheral signals and modulation of those signals in the central nervous system by descending inhibitory and facilitatory systems.40 A dysregulated pattern of endogenous pain modulation, characterized by greater facilitation of pain and a reduced capacity to inhibit pain on dynamic quantitative sensory tests, is a shared characteristic of many chronic pain syndromes (eg, fibromyalgia, back pain, and osteoarthritis17,19,26,41), is associated with increased reports of clinical pain in healthy adults,9,11 and predicts the transition from acute to chronic postoperative pain.47 Accumulating evidence indicates that aging is associated with a dysregulated pain profile as well,9,10,13,24,28,31 and the age-related imbalance of pain inhibition and facilitation places older adults at a greater risk of developing chronic pain compared with younger adults. Alarmingly, the prevalence estimates of chronic pain among the elderly may be as high as 60% to 75% in the United States.20 Determining modifiable and behavioral factors contributing to this dysregulated pattern of pain modulation in older adults is crucial to the development of strategies to prevent persistent pain in older people.

A growing body of evidence has begun to link physical activity behavior to endogenous pain modulatory function,12,18,30,43 with generally more efficacious pain modulation observed in more active individuals. Importantly, older adults are the least physically active cohort of all age groups.29 Reduced physical activity facilitates the aging process and physiological decline, and hence could play an important role in the decline of endogenous pain inhibitory and facilitatory systems observed in older adults. Supporting this notion, we recently showed that self-reported levels of vigorous and total physical activity were related to the functioning of endogenous pain modulatory systems in healthy younger and older adults.30 Individuals who reported more vigorous and total physical activity demonstrated enhanced pain inhibition during the conditioned pain modulation test and less temporal summation (TS) of pain. However, a major limitation of this study was that physical activity was assessed by a questionnaire rather than by objective methods, which often results in highly variable estimations of the amount of physical activity reported.16,28 In addition, only a portion of the participants were older adults. Thus, studies using objective measures of physical activity are needed to substantiate the relationship between physical activity behavior and endogenous pain modulatory function in a full sample of older adults.

The purpose of this study was 2-fold. We sought to determine whether objective measures of physical activity in healthy older adults predicted (1) pain facilitatory function as tested by TS of pain, and (2) pain inhibitory function as tested by conditioned pain modulation (CPM). Temporal summation of pain and CPM are the 2 most extensively studied dynamic quantitative sensory tests and are considered human behavioral correlates of ascending facilitatory and descending inhibitory limbs of central pain modulation, respectively.1 We hypothesized that older adults who did greater amounts of moderate to vigorous physical activity (MVPA) would exhibit reduced TS of pain, and greater inhibition of pain on the CPM test.

2. Methods

2.1. Participants

Participants were 51 healthy adults ranging in age from 60 to 77 (males = 21, females = 30). Table 1 presents the descriptive characteristics of the sample. The racial composition of the sample included 46 Caucasians, 1 Hispanic, and 4 African Americans. A power analysis using G Power 3.1.5 was used to estimate the sample size needed for predicting TS and CPM in a linear regression model. Preliminary data indicate strong associations between self-reported physical activity and pain modulation (r = 0.51, r = 0.70). Using the lowest value for calculation of power (0.51) and including 2 covariates, a sample size of 48 would provide power of 0.80 at 0.05 (2 tailed).

Table 1:
Means and SDs for primary study measures in male and female participants.

Participants were recruited through posted advertisements in the local community. Individuals meeting any of the following criteria were excluded from the study: (1) the current use of narcotics or any tobacco products, chronic use of analgesics, (2) serious systemic disease or condition that restricted normal daily activities (eg, 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 6-Item Cognitive Impairment Test, (4) uncontrolled hypertension, (5) cardiovascular, metabolic, or pulmonary disease, (6) neurological disease, (7) serious psychiatric conditions (eg, schizophrenia and bipolar disorder), and (8) chronic pain or any ongoing pain problem (headaches, injury-related pain, etc.). In addition, participants were instructed to refrain from consuming caffeinated beverages or any pain medications before the experimental sessions. All participants completed one screening and orientation session and 3 experimental sessions on separate days.

2.2. Screening and orientation session

This study was approved by the Indiana University Human Subject Review Board. The screening and orientation session lasted approximately 2 hours and occurred on a separate day than the experimental sessions. All participants were provided information about the experimental procedures, and reviewed and signed an informed consent form approved by the Indiana University Institutional Review Board before participating 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 6-item Cognitive Impairment Test5 to ensure that participants were free of cognitive impairment that would compromise study participation. 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 test stimulus of the conditioned pain modulation protocol such that participants would experience moderate pain (40-60 on a 0-100 numeric rating scale). Participants also completed the State-Trait Anxiety Scale–Trait version and Pain Catastrophizing Scale. At the end of the training session, participants were given an accelerometer, instructions on how to wear the device, and a physical activity diary.

2.3. 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 0.05 to 2 G. Output from the ActiGraph is in the form of step counts, body positions, and activity counts for a specific period. Data were captured in 1-minute epochs, and nonwear time was defined as 60 minutes 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 7 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 hours. 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 reminder calls or emails from research staff about wearing the accelerometers.

Activity count cutpoints to determine the amount of time a participant spent in sedentary, light, or moderate to vigorous activity were defined as <100 counts/min (sedentary), 100 to 1951 counts/min (light physical activity [LPA]), and >1951 counts/min (moderate to vigorous activity), respectively.14 These cutpoints have been used by other studies to measure physical activity behavior in older adults.2,4 Data for all categories were expressed in min/d, and all light and sedentary data were adjusted for wear time by its inclusion as a covariate in the regression models.

2.4. Quantitative sensory testing

The experimental quantitative sensory tests were conducted on three separate sessions which occurred after participants wore the accelerometers. These sessions were separated by at least 48 hours but within a 3-week time frame. The TS of heat pain test was conducted during each of the three experimental sessions and was always the first Quantitative sensory testing test conducted during each individual session. Scores for the TS measures were averaged across all 3 sessions to provide the best representation of TS of pain for each participant. The CPM test was conducted only during one of the experimental sessions, with the CPM test always administered at least 15 minutes after the TS test. On the 2 experimental sessions in which CPM was not conducted, other measures were taken which are not reported here.

2.4.1. Temporal summation of heat pain

Temporal summation refers to the increased perception of pain in response to repetitive noxious stimuli delivered at frequencies above 0.3 Hz.33,34 Brief repetitive suprathreshold heat pulses were delivered to the right and left ventral forearms by a Peltier-based thermode (32 × 32 mm; TSA-II; Medoc Advanced Medical Systems, Durham, NC). Each trial consisted of a series of 5 heat pulses, with each pulse delivered at a rate of 10°C/s. The peak-to-peak interpulse interval was approximately 2.5 seconds. The baseline temperature was 34°C to 38°C, and the target temperature was either 44°C, 46°C, or 48°C. The lowest baseline temperature corresponded to the lowest target temperature to keep the same 10°C increase step for pulses of each trial. Participants were instructed to rate the intensity of the late pain sensations experienced after each pulse (ie, pain felt between the pulses not during each pulse, termed second pain) with a 0 to 100 numeric rating scale, with “0” indicating no pain and “100” indicating “intolerable pain.” Two trials (one on each forearm) at each temperature (44°C, 46°C, and 48°C) were administered to each participant during each session, with at least 1 minute between trials. The order of trials for each temperature was randomized for each participant but kept constant across sessions. A TS score was calculated by subtracting the pain rating after the first pulse from the highest interpulse pain rating.6,22 This score captures the maximum amount of TS across the 5 pulses. An average TS score was calculated for each temperature across the 3 sessions and used for data analysis.

2.4.2. Conditioned pain modulation

The most frequently used test of endogenous pain inhibition is conditioned pain modulation. CPM refers to the reduction of pain produced by a test stimulus by a second noxious conditioning stimulus in a remote body site (ie, “pain-inhibition-by-pain”).46 For CPM trials, pressure and heat pain sensitivity (as described below) were measured before and immediately after a conditioning stimulus. Seven minutes separated the prepain assessments and the initiation of the conditioning stimulation, during which participants sat quietly. Conditioning stimuli

The conditioning stimulus consisted of 3 × 45-second consecutive trials separated by 15-second rest periods (3 minutes total). Similar cold water immersion procedures have been used for studies showing age differences in CPM.32,36 For each 45-s trial, participants placed their right hand up to the wrist in a cold water bath recirculated and cooled by a refrigeration unit to 10°C (VersaCool 7; Thermo Scientific, Asheville, NC). Participants continued until the end of that trial or until they reported intolerable pain. Participants also rated the intensity of cold pain every 15 seconds during the cold water immersion with the same 0 to 100 numeric rating scale used for the TS trials. The pain ratings were averaged across time for a single cold water immersion pain score for each participant. Test stimuli

Two test stimuli were administered consecutively before and after the conditioning stimulus. The first test stimulus was pressure pain thresholds (PPTs). 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) to the left ventral forearm. Participants were instructed to press a 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-conditioning test. These trials were averaged for a single pre- and post-test PPT score. The second test stimulus was a continuous heat pain test, where focal thermal stimuli (44°C-49°C) were administered by a Peltier-based thermode (TSA-II, Medoc; thermode size: 30 × 30 mm) to the forearm. For each 30-second continuous heat pain trial, the thermode was first brought to a neutral temperature (32°C) and then ramped (2.0°C/s) to the individualized temperature (44°C-49°C) determined during the training session and maintained at that temperature for 30 seconds. 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 (100 mm 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. Two trials were administered consecutively with a 1-minute intertrial-interval during each pre- and post-conditioning test. The average pain rating for each 30-s trial was calculated. The pre- and post-conditioning test trials were averaged for a single pre- and post-conditioning test heat pain score. Calculation of conditioned pain modulation

A percent change score was calculated for each test stimulus (CPM-PPT and CPM-Heat) with the following formula: ([post CPM trial score − pre CPM trial score]/pre CPM trial score) × 100. For the CPM-Heat, a negative percent change score indicated a reduction in pain after the conditioning stimulus and thus pain inhibition. For the CPM-PPT, a positive percent change score indicated an increase in PPTs after the conditioning stimulus and thus pain inhibition.

2.5. Psychological questionnaires

2.5.1. State-Trait Anxiety Inventory–Trait version (STAI-T)

The STAI39 has extensive normative data and is a frequently used measure of anxiety in pain studies. The Trait-Anxiety subscale consists of 20 items that evaluate how respondents feel in general. Higher scores indicate greater trait anxiety.

2.5.2. Pain Catastrophizing Scale

The Pain Catastrophizing Scale42 consists of 13 items rated on a 5-point likert scale. The PCS asks the respondents to reflect on 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.

2.6. Data analysis

Descriptive statistics were calculated for age, STAI-T score, PCS score, thermode test temperature for the 30-s heat trials, TS at 44°C, 46°C, and 48°C, cold water bath pain ratings, CPM-Heat score, CPM-PPT score, and average time per day spent in LPA, MVPA, and sedentary behavior. Shapiro–Wilk test of normality indicated that all the data except for the CPM scores were not normally distributed; thus Mann–Whitney U tests were conducted to determine if theses variables differed by sex. Independent t-tests were conducted to determine whether CPM-Heat and CPM-PPT differed by sex. Additionally, pair-wise t-tests were conducted to determine whether participants exhibited significant TS of heat pain at each temperature (first pulse vs max pulse rating), and CPM with each test stimulus (average score for preconditioning test vs average score for postconditioning test).

We conducted spearman bivariate correlations between TS and CPM scores and psychological and physical activity variables. Additionally, hierarchical linear regressions were performed to determine the relationship between physical activity and TS and CPM, while controlling for factors known to influence experimental pain testing. Sex and body mass index (BMI) were entered into the first block. For regressions on CPM-Heat, thermode test temperature was added into the second block. Pain catastrophizing and Trait anxiety scores were entered into the third block for CPM-Heat regressions and the second block for CPM-PPT and TS regressions. Accelerometer wear time was entered as a predictor for any analysis involving sedentary time or LPA. Light physical activity, MVPA, or sedentary time were always entered into the last block for each regression. Separate regressions were conducted for each CPM- and TS-dependent variable with each of the physical activity variables as the final predictor.

3. Results

Participant characteristics are presented in Table 1. Males exhibited significant greater sedentary time per day compared with females, P = 0.04. No other significant differences existed between males and females on any of the study variables (p's > 0.05). Pair-wise t-tests indicated that significant TS of pain occurred for the 44°C trials (P < 0.001; max pulse pain rating = 15.7 ± 15.7 vs first pulse rating = 14.7 ± 15.2), the 46°C trials (P < 0.001; max pulse pain rating = 20.2 ± 18.8 vs first pulse rating = 18.3 ± 17.9), and the 48°C trials (P < 0.001; max pulse pain rating = 30.5 ± 22.3 vs first pulse rating = 25.6 ± 20.6). Significant CPM was found with the heat test stimulus (P = 0.003), with the average pain rating for the postconditioning heat trial (M = 23.2 ± 15.7) less than the average pain rating for the preconditioning heat trial (M = 27.9 ± 17.7). Sixty-two percent of participants exhibited some level of pain reduction on the heat test after the conditioning stimulus. Significant CPM was not observed with the PPT test stimulus (P = 0.582: preconditioning PPT = 348.5 ± 167.7 kPa vs postconditioning PPT = 354 ± 167.7 kPa). However, 56% of participants exhibited some level of increase in PPT after the conditioning stimulus. All participants wore the accelerometer for at least 5 valid days.

3.1. Bivariate correlations

As displayed in Table 2, MVPA was significantly associated with TS at 46°C, such that those doing more MVPA per day had less TS of pain. CPM-Heat was negatively correlated with CPM-PPT and positively correlated with TS at each temperature, indicating that those experiencing greater pain inhibition during the heat test-stimulus also experienced greater pain inhibition during the pressure test-stimulus and less TS. CPM-Heat was also negatively associated with LPA. Those who did more LPA per day exhibited greater pain inhibition on the CPM-Heat test.

Table 2:
Bivariate correlation matrix between primary study measures.

3.2. Hierarchical regressions

After controlling for sex, BMI, and psychological variables, MVPA predicted TS at each temperature (See Table 3) accounting for 11% to 16% of the variance. Older adults who did more MVPA per day exhibited less TS of pain. No models with sedentary time or LPA as the final predictors were significant for the prediction of TS (p's > 0.05).

Table 3:
Summary of hierarchical regression analyses for TS at 44°C, 46°C, and 48°C with MVPA as final predictor.

Hierarchical regressions revealed that after controlling for sex, BMI, thermode temperature, psychological variables, and accelerometer wear time, sedentary time predicted CPM-Heat (Table 4A), accounting for 25.5% of the variance. In addition, in a separate regression analysis (Table 4B), LPA also predicted CPM-Heat accounting for 20% of the variance. Individuals who did more LPA or had less sedentary time per day exhibited greater pain inhibition during the CPM test. Although MVPA (Table 4C) was an individually significant predictor of CPM-Heat, the overall model was not significant. No models for the prediction of CPM-PPT were significant (p's > 0.05).

Table 4:
Summary of hierarchical regression analyses for CPM-Heat with sedentary time, LPA, and MVPA as final predictors.

4. Discussion

This study provides the first objective evidence suggesting that physical activity behavior is related to the functioning of the endogenous pain modulatory systems in healthy older adults. Specifically, 2 key findings emerged from the data. First, the amount of MVPA per day predicted pain facilitatory function as measured by TS of pain. Second, sedentary behavior and light, rather than moderate to vigorous, physical activity predicted pain inhibitory function as measured by CPM. These results highlight the significance of considering physical activity behavior when examining experimental models of pain modulation between different populations of people (eg, young vs old), particularly given that many older adults and individuals with chronic pain are deconditioned and sedentary.

4.1. Temporal summation of pain and physical activity behavior

As hypothesized, older adults who did more MVPA per day exhibited less TS of heat pain, regardless of the thermode temperature. As indicated by the R2 values, the effect of MVPA on TS was medium in size,8 even after accounting for sex, BMI, and psychological status of participants. This result is in line with our recent study showing that self-reported vigorous physical activity was related to TS of heat pain in healthy adults.30 The progressive increase in pain intensity on the TS test represents a behavioral correlate of “wind-up” of spinal dorsal wide dynamic range neurons and is often used as an indirect marker of central sensitization.33,34 Enhanced facilitation of pain on the TS test is a characteristic of many chronic pain syndromes common in older adults (ie, osteoarthritis, low back pain17,19) and thought to be a risk factor for the development of chronic pain. Thus, older adults participating in relatively low levels of MVPA may be at an increased risk for central sensitization. Consequently, participation in MVPA could be a promising strategy to attenuate pain facilitatory processes and potentially decrease the risk for development of chronic pain in older adults.

The exact biological mechanisms underlying the age-related increase in pain facilitatory processes remains unknown; however, several mechanisms could exist through which MVPA influences pain facilitatory processes in older adults. For example, aging is associated with a state of chronic low-grade systemic inflammation37 and elevated levels of oxidative stress,23 and multiple studies have demonstrated that oxidative stress15,25 and proinflammatory cytokines21,38 induce sensitization of the peripheral and central nervous systems through several pathways. Notably, regular aerobic exercise has anti-inflammatory and antioxidant effects,35,45 that could impede the processes that lead to central sensitization (ie, increased TS of pain). However, future studies are needed to test these mechanistic hypotheses.

4.2. Conditioned pain modulation and physical activity behavior

Several studies indicate that older compared with younger adults have reduced efficacy of endogenous pain inhibition on the CPM test.10,36 Previous research using the CPM test also shows that a reduced pain inhibitory capacity is a shared characteristic of many chronic pain syndromes,26 is associated with increased reports of clinical pain in healthy adults,11 and predicts the transition from acute to chronic postoperative pain.47 As such, ineffective descending pain inhibition could place older adults at an increased risk for chronic pain. Our results suggest that sedentary behavior and LPA in older adults are strong predictors of pain inhibitory function on the CPM test, even after controlling for confounding factors. Older adults who had relatively less sedentary time per day and did more LPA exhibited greater pain inhibition on the CPM-Heat test. It should also be noted that, although CPM-Heat was correlated with CPM-PPT, we found no relationship between CPM-PPT and physical activity behavior in this study. As recommended by Yarnitsky et al.,46 we included 2 types of test stimuli in the CPM protocol (ie, 30-s heat stimulus and PPT). While only speculation, differences in the effect of physical activity behavior on CPM-Heat vs CPM-PPT could be related to the different sources of pain stimulation or intensity of stimuli (suprathreshold [CPM-Heat] vs threshold [CPM-PPT] pain).

The notion that pain inhibitory function is related to physical activity behavior has been supported by cross-sectional studies in healthy younger adults,30,43 triathletes,18 and patients with fibromyalgia.12 Both Umeda et al. and Naugle et al. found that greater vigorous physical activity was associated with more efficient conditioned pain modulation in healthy adults. Given that these studies consisted of primarily younger adults, it is plausible that the relationship between physical activity behavior and central pain modulation changes as people age. In support of the relationship between sedentary behavior and pain modulation, Ellingson and colleagues found that patients with fibromyalgia who spent relatively more time in sedentary behavior were less able to modulate pain during distraction.12 Furthermore, sustained sedentary behavior had a negative relationship with brain responses in areas involved in pain modulation. Although the acute and long-term effects of sedentary behavior on pain outcomes have not been widely documented, sedentary behavior has emerged as a new and potent risk factor for mortality and many health conditions, irrespective of the time spent in MVPA.44 Alarmingly, the most sedentary group in the United States is older adults aged >60 years, with up to 80% of their awake time spent in sedentary activities.29 Our data suggest that low levels of sedentary behavior and greater LPA may be critical in maintaining effective endogenous pain inhibitory function in older adults.

Research on the effects of sedentary behavior and LPA on pathophysiological pain mechanisms are currently sparse; nonetheless, the available evidence may be able to shed some light on how these behaviors could be linked to pain inhibitory function. Indeed, a recent study showed that altered responsiveness in the prefrontal and cingulate cortices predicted reduced CPM in individuals with chronic pain.48 Importantly and as mentioned earlier, Ellingson et al.12 found that sedentary behavior in patients with chronic pain was associated with reduced pain modulation during a cognitive task and altered brain responses in the prefrontal and cingulate cortices during pain modulation. Hence, a sedentary lifestyle could have detrimental effects on brain function integral to the descending inhibition of pain. Another potential mechanism involves increases in the availability of serotonin in the central nervous system with LPA. Animal models and human studies suggest that CPM is greatly dependent on the integrity of the descending bulbospinal serotonergic systems.7,27 Furthermore, a recent animal study showed that regular low intensity exercise suppresses pain-like behaviors in animals with neuropathic pain by enhancing the availability of serotonin in the central nervous system.3 Nonetheless, the proposed mechanisms are clearly speculative and additional research is needed to explore the biological mechanisms through which physical activity behavior may improve or deteriorate pain modulatory function.

4.3. Limitations and future directions

Several limitations of this study need to be acknowledged. First, the cross-sectional nature of the study renders it possible that dysfunctional pain modulation leads to reduced physical activity and greater sedentary behavior. Future longitudinal research is needed to verify the causal relationship between physical activity behavior and endogenous pain facilitatory and inhibitory function. In particular, intervention studies examining manipulations of both exercise and sedentary behavior are needed to determine the unique and overlapping pathways of these behaviors contributing to altered central pain modulation. Second, the sample of participants in this study consisted of healthy older adults, who were primarily Caucasian and likely more active than the average older adult. Therefore, generalization of the results to older adults with chronic pain conditions and of other ethnic backgrounds may be limited. Third, physical activity behavior was only assessed over a 7-day period, which may not have been representative of overall physical activity habits for each participant. Fourth, based on our power analysis, this study was sufficiently powered to conduct a linear regression model with 2 covariates. Given that our regression models contained more than 2 covariates, it is possible that with a larger sample size the model with MVPA predicting CPM-Heat would have been significant.

In conclusion, we provide evidence that different types of physical activity behavior may differentially impact pain inhibitory and facilitatory processes in older adults. Specifically, sedentary behavior and LPA seem to be related to pain inhibitory capacity in older adults, whereas MVPA is associated with pain facilitatory processes. Future research should determine whether the effectiveness of physical activity interventions to reduce and prevent pain in older adults could be maximized by coupling the dysfunctional pain modulation pattern observed in older adults with the type of physical activity that can improve that dysfunction.

Conflict of interest statement

The authors have no conflicts of interest to declare.

This research was supported by the IUPUI School of Physical Education and Tourism Management Faculty Research Opportunity Grant.


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Physical activity; Aging; Conditioned pain modulation; Temporal summation of pain

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