Indian Journal of Pain

: 2021  |  Volume : 35  |  Issue : 2  |  Page : 157--161

Correlation of endogenous pain modulation function with physical activity in elders having chronic pain

Alifiya S Sirohiwala1, Gloria Alva2, Shaswat Verma2,  
1 Clinical Physiotherapist, Interim Physiotherapist, Neurofunction Rehab, Surrey, Canada
2 Department of Physiotherapy, MS Ramaiah Medical College, Bengaluru, Karnataka, India

Correspondence Address:
Asst. Prof. Shaswat Verma
Department of Physiotherapy, MS Ramaiah Medical College, Bengaluru-560054, Karnataka


Context: Chronic pain is a major predicament of the elderly population and lacks appropriate treatment. In normal healthy individuals, physical activity (PA) shows an effect on endogenous pain modulation (EPM) function by producing central opioids and producing exercise-induced analgesia. Aims: This study aimed to determine a correlation between EPM function and PA of the elderly having chronic pain. Methodology: This was a cross-sectional study of 45 elderly individuals who were between 60 and 80 years of age, suffering from chronic pain. The EPM function was tested using conditioned pain modulation test and PA levels were obtained using Yale Physical Activity Survey (YPAS). In addition, we collected demographic details, duration of pain, and site of pain from the study population. Descriptive statistics was depicted in terms of frequency. Categorical variables were indicated as the mean and standard error of mean. The Spearman's rank correlation (r) test was used to find the correlation between conditioned pain modulation (CPM) and YPAS score. Results: A positive moderate correlation was found between EPM function and PA of elderly having chronic pain (r = 0.05; P = 0.0002). Analysis of EPM function based on the gender of the study population showed that both females (22.54 ± 23.92) and males (6.24 ± 29.19) had similar EPM function values. YPAS score was found as a significant predictor of CPM (P = 0.0003). Conclusion: There is a positive moderate correlation between EPM function and PA levels of elderly having chronic pain.

How to cite this article:
Sirohiwala AS, Alva G, Verma S. Correlation of endogenous pain modulation function with physical activity in elders having chronic pain.Indian J Pain 2021;35:157-161

How to cite this URL:
Sirohiwala AS, Alva G, Verma S. Correlation of endogenous pain modulation function with physical activity in elders having chronic pain. Indian J Pain [serial online] 2021 [cited 2022 Jan 19 ];35:157-161
Available from:

Full Text


Chronic pain is a universal problem that lacks significant recognition among the community-dwelling and institutionalized elderly.[1] Chronic pain has traditionally been defined as pain lasting for more than 3–6 months.[2] Studies done on a larger population reveal that physical activity (PA) affects the development of chronic pain. Individuals who have more PA are less likely to develop chronic pain.[3],[4] Compared to younger adults, older adults have a lesser capacity to inhibit pain endogenously and are characterized by higher endogenous pain facilitation.

Newer studies have used an experimental test named conditioned pain modulation (CPM) to examine endogenous pain modulatory processing within the central nervous system (CNS).[5],[6] CPM test is commonly used to assess endogenous pain modulation (EPM). In this technique, a painful test stimulus is evaluated in the absence and presence of a second painful (conditioning) stimulus applied to a remote region of the body.[7] Factors such as gender[8] and level of PA are known to affect CPM.[9]

The Yale Physical Activity Survey (YPAS) is an interviewer-administered questionnaire that is developed to determine the type, amount, and pattern of PA in older adults.[10] Studies say that inactivity is a risk factor for the development of chronic pain,[3] and an increase in PA reduces the symptom severity in patients with chronic pain.[11] A single bout of exercise is found to reduce sensitivity to experimental pain as suggested by various experimental studies.[12] This phenomenon is named as exercise-induced hypoalgesia in literature, suggesting that a variety of exercise protocols which differ in mode, duration, and intensity are capable of increasing pain tolerance level and reduction in pain ratings before and after exercise.[13] The current study aimed at determining the PA, EPM function, and to determine a correlation between EPM function and PA levels in the elderly having chronic pain.


The present cross-sectional study was conducted among 45 elderly individuals aged between 60 and 80 years with chronic pain in the outpatient department of a tertiary care hospital. After obtaining institutional ethical approval, the purpose of the study was explained to each patient and informed consent was obtained.

Elderly patients of either gender aged >60 years and having chronic pain in the lower limb for >3 months were included in the study. Elderly individuals who underwent recent surgeries and were on chronic use of analgesics and individuals with stroke, spinal cord injury, peripheral vascular disease, diabetic neuropathy, cancer, Alzheimer's disease, and bipolar disorders were excluded from the study. Convenience sampling method was used in this study to select the subjects for the study.

Demographic details of the study participants, duration of pain, and site of pain were also collected. Chronic pain engaging CNS pain inhibitory systems termed as EPM was measured. The EPM function was tested using CPM test, and PA levels were obtained using YPAS score. Based on the metabolic equivalent of tasks value calculated using the questionnaire YPAS, the participants were classified to sedentary (1–1.5), light (1.6–2.9), moderate (3.0–5.9), and vigorous (>6) levels of PA.

EPM measured by CPM test was assessed by measuring responses to phasic noxious stimuli before, during, and after heterotopic application of a tonic noxious stimulus. The conditioning stimulus consisted of 1 trial of 45 s cold water immersion procedure. For 45 s trial, participants placed their hands up to the wrist in a cold water bath cooled by a refrigeration unit to 10°C measured by a clinical thermometer. Participants continued until the end of that trial or until they reported intolerable pain. The test stimuli was pain pressure threshold (PPT) measured by a digital, handheld, clinical-grade pressure algometer. The tip of the algometer consisted of a rubber flat 1.0 cm2 probe. The experimenter applied a slow constant pressure to the right ventral forearm and was instructed to inform when the pressure sensation first became painful. PPT was defined as the amount of pressure (kgLb) at which the participant first reported experiencing pain at which the algometer was removed. The same procedure was followed postconditioned stimuli and the percent change score was calculated with the following formula: ([post-PPT trial score − pre-PPT trial score]/pre-PPT trial score × 100).

Statistical analysis

Based on a previous study,[14] the correlation between the PA levels and EPM was found to be 0.47, expecting similar results in our study with 85% power and 95% confidence level, the study requires a minimum of 33 subjects. Hence, we included a total of 45 subjects in the study.

Categorical variables were represented as mean and standard deviation. The correlation between two continuous variables (EPM function and PA) was analyzed using Spearman's rank correlation test in terms of Spearman's rank correlation coefficient value (r value). Multiple linear regression analysis was performed to determine the predictors of CPM.


This study included 45 elderly individuals with ≥60 years of age, of which 23 (51.1%) were male and 22 (48.9%) were female. The mean age of the study population was found to be 66.60 ± 6.56 years. The mean and standard deviation for CPM and YPAS scores were found to be 14.45 ± 27.45 and 2.79 ± 2.574, respectively [Table 1].{Table 1}

This study divided 45 elderly individuals having chronic pain into four categories based on the PA level as sedentary (n = 11; 24.4%), light (n = 19; 42.2%), moderate (n = 11; 24.4%), and vigorous (n = 4; 8.9%). In males, 40.91% had sedentary, 36.36% had light, and 22.73% had moderate PA levels. In females, 8.7% had sedentary, 47.83% had light, 20.09% had moderate PA levels, and 17.39% had PA levels [Figure 1].{Figure 1}

Post-PPT, CPM score, and YPAS score were differed significantly with respect to PA levels [P < 0.05; [Table 2]]. YPAS score and chronicity differed significantly between males and females [P < 0.05; [Table 3]].{Table 2}{Table 3}

Spearman rank correlation was used to find the correlation between CPM and YPAS score. In this study, a positive moderate correlation was identified between CPM and YPAS score [r = 0.52; P = 0.0002; [Figure 2]].{Figure 2}

The mean and standard deviation of PPT pre, PPT post, CPM, and YPAS were analyzed, as shown in [Table 3]. Almost similar findings of PPT pre, PPT post, CPM, and YPAS were noticed in both males and females.

YPAS score was found as a significant predictor of CPM. One unit increase in YPAS score is associated with 5.7415 times increase in CPM holding age, gender and chronicity constant. In addition, age, gender, and chronicity were not significant predictors of CPM [Table 4].{Table 4}


The present study provides evidence supporting the correlation of EPM function in the elderly with their PA level. As we know, there is an age-related increase in the prevalence of chronically painful conditions such as arthritis, fibromyalgia, herpes zoster, and trigeminal neuralgia that can contribute to poor quality of life and enhanced disability in the elderly.[1] Elderly individuals with chronic pain are sedentary and de-conditioned which is characterized by greater endogenous pain facilitation and a reduced capacity to endogenously inhibit pain, which increases their risk for developing chronic pain.[9] Geriatric chronic pain is a significant problem that needs to be addressed as it is a major contributor to poor quality of life, reduced well-being, physical disability, and mortality. Exercise is an effective treatment for reducing chronic pain and PA is reduced in people with chronic pain.[9] Thereby, the origin of this study was based on a hypothesis that EPM function will have a correlation with PA levels of elderly individuals suffering from chronic pain.

The descending modulation from the brainstem has a strong influence on the conduction of nociceptive input from the spinal cord to supraspinal centers. The Diffuse Noxious Inhibitory Controls (DNIC) system that is located in the caudal medulla provides one of the main descending pain inhibition pathways. This system is activated when a painful stimulus is introduced in the body. The DNIC system focuses pain sensation on the stimulus by reducing the concurrent pain input from remote sites of the body. Pain inhibition at anatomical regions of the body distant to where the new pain was introduced indicates activation of the DNIC system. The measurement of DNIC function has widespread clinical relevance as presence of an impaired EPM function may place people at a potential risk of developing chronic pain conditions.[15]

The experience of pain depends on how CNS interacts and modulates ascending peripheral signals by descending inhibitory and facilitatory systems. Many chronic pain syndromes like fibromyalgia, back pain, and osteoarthritis have a dysregulated pattern of EPM, characterized by greater facilitation of pain and a reduced capacity to inhibit pain on dynamic quantitative sensory tests. Various studies are present that suggest association between aging and dysregulate pain inhibition and facilitatory systems and this places older adults in comparison to young adults at a greater risk of suffering from chronic pain due to an imbalance of pain inhibition and facilitation system.[9]

Activation of central inhibitory pathways that produce an opioid-mediated analgesia is believed to be activated with exercise. The central nucleus of these pathways is the rostral ventromedial medulla (RVM) as there is an increase in release of endogenous opioids in brainstem nuclei, including RVM, during exercise and blockage of central pain. The study conducted in physically active animals with chronic pain evidenced decrease in phosphorylation of N-methyl-D-aspartate (NMDA) receptors and stated regular PA prevents development of chronic pain and activation of central neurons. The NMDA receptors present in the RVM are critical for the development of hyperalgesia after muscle insult; thus, blockade of NMDA receptors reduces hyperalgesia and prevents chronic muscle hyperalgesia. Further, there is a central release of endogenous opioids that occurs in physically active in animals with chronic pain, thus suggesting that regular exercise reduces pain by activation of opioid receptors in descending inhibitory pathways of CNS.[16]

Our study results also highlight the significance of considering levels of PA among elderly individuals as 66% of elderly had sedentary to light PA which implies that majority of elderly individuals were physically inactive and were at higher risk of having chronic pain. These findings are in coincidence with the findings of another study,[16] which suggests that PA is a major contributor for developing chronic pain. Research on the effects of sedentary behavior and low PA on pathophysiological pain mechanisms are currently sparse, but the available evidence may be able to explain us how these PA behaviors are linked to EPM function. Previous literature also stated that altered responsiveness in CNS predicts the reduction CPM efficacy in individuals with chronic pain. Moreover, there is reduced pain modulation during a cognitive task and altered brain responses during the EPM were found to be associated with sedentary behavior in patients with chronic pain. Hence, the integral brain function of EPM could be affected due to a sedentary lifestyle.

EPM function was similar in both females (22.54 ± 23.92) and males (6.24 ± 29.19) in this study. On the contrary,[17] another study concluded that a higher EPM effect was found in males in comparison to females. Gender differences in EPM function may depend on the methodology of the experiment and the mode of measurement of the function. Thus, future studies should have standardized experimental protocols for measuring function that permits comparison among various studies and better meta-analysis to arrive at a proper conclusion.

Indeed, there are clinical studies that show that patients' attitudes and emotions influence pain perception. For example, chronic pain intensity was found to positively correlate with overall affective distress and postoperative dental pain was found to positively correlate with preoperative anxiety. In the experimental setting, improving the emotional state induced a reduction in perceived pain, whereas inducing negative emotions induced an increase in perceived pain.[7] As there is scarce evidence on the association of psychosocial factors in the elderly with chronic pain and their PA levels and the mechanism by which the EPM function is influenced by psychosocial factors. This could be a recommendation for future studies and is of very important clinical relevance for treating and preventing chronic pain in elderly individuals.

The main limitations of this study were that first, the measuring tool used for PA was very subjective as it was a self-reported questionnaire. Second, elderly population are prone to have poor memory which could have led to recall bias and could have affected the study results as they had to report their findings of a typical last week. Third, a lack of an objective measuring tool could have led to overestimation or underestimation of PA levels. Fourth, there were a lot of test-re-test reliability issues with CPM test that could have affected the study result. Fifth, BMI and patients with osteoporosis, muscular atrophy, and other associated conditions need to be considered in future research to see how EPM is affected by PA levels in patients with chronic pain. Last, the population was selected using a convenience sampling method that would limit it from further generalizing the findings of the whole population.


Numerous studies have provided us with evidence that PA has a beneficial role in influencing chronic pain symptoms in elderly individuals. Furthermore, our study results showed a positive correlation between the EPM function and PA levels in the elderly with chronic pain which suggests that PA may have a protective effect against the decline in EPM function in elderly with chronic pain.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


1Edwards RR, Fillingim RB. Effects of age on temporal summation and habituation of thermal pain: Clinical relevance in healthy older and younger adults. J Pain 2001;2:307-17.
2Carette S. Chronic pain syndromes. Ann Rheum Dis 1996;55:497-501.
3Landmark 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 2011;152:2241-7.
4Zhang R, Chomistek AK, Dimitrakoff JD, Giovannucci EL, Willett WC, Rosner BA, et al. Physical activity and chronic prostatitis/chronic pelvic pain syndrome. Med Sci Sports Exerc 2015;47:757-64.
5Yarnitsky D. Conditioned pain modulation (the diffuse noxious inhibitory control-like effect): Its relevance for acute and chronic pain states. Curr Opin Anaesthesiol 2010;23:611-5.
6Yarnitsky D, Arendt-Nielsen L, Bouhassira D, Edwards RR, Fillingim RB, Granot M, et al. Recommendations on terminology and practice of psychophysical DNIC testing. Eur J Pain 2010;14:339.
7Lewis GN, Heales L, Rice DA, Rome K, McNair PJ. Reliability of the conditioned pain modulation paradigm to assess endogenous inhibitory pain pathways. Pain Res Manag 2012;17:98-102.
8Bulls HW, Freeman EL, Anderson AJ, Robbins MT, Ness TJ, Goodin BR. Sex differences in experimental measures of pain sensitivity and endogenous pain inhibition. J Pain Res 2015;8:311-20.
9Naugle KM, Ohlman T, Naugle KE, Riley ZA, Keith NR. Physical activity behavior predicts endogenous pain modulation in older adults. Pain 2017;158:383-90.
10Colbert LH, Matthews CE, Havighurst TC, Kim K, Schoeller DA. Comparative validity of physical activity measures in older adults. Med Sci Sports Exerc 2011;43:867-76.
11Arai YC, Kazuhiro Shimo P, Jun Sato M, Tomoaki Osuga M, Makoto Nishihara M, Takahiro Ushida M. Effects of cognitive-behavioral therapy on pain intensity and level of physical activity in Japanese patients with chronic pain-a preliminary quasi-experimental study. J Phys Ther 2010;1:49-57.
12Koes BW, van Tulder M, Lin CW, Macedo LG, McAuley J, Maher C. An updated overview of clinical guidelines for the management of non-specific low back pain in primary care. Eur Spine J 2010;19:2075-94.
13Umeda M, Lee W, Marino CA, Hilliard SC. Influence of moderate intensity physical activity levels and gender on conditioned pain modulation. J Sports Sci 2016;34:467-76.
14Naugle KM, Riley JL 3rd. Self-reported physical activity predicts pain inhibitory and facilitatory function. Med Sci Sports Exerc 2014;46:622-9.
15Yarnitsky D, Crispel Y, Eisenberg E, Granovsky Y, Ben-Nun A, Sprecher E, et al. Prediction of chronic post-operative pain: Pre-operative DNIC testing identifies patients at risk. Pain 2008;138:22-8.
16Sluka KA, O'Donnell JM, Danielson J, Rasmussen LA. Regular physical activity prevents development of chronic pain and activation of central neurons. J Appl Physiol (1985) 2013;114:725-33.
17Popescu A, LeResche L, Truelove EL, Drangsholt MT. Gender differences in pain modulation by diffuse noxious inhibitory controls: A systematic review. Pain 2010;150:309-18.