After adjusting for the confounder variables (SQ and PA levels), the final multivariate model (model 1) demonstrated a significant positive association of the daily estimates of SB with the CPM30sec. However, the backward multiple regression model showed significant positive associations of SB with CPM30sec response (model 4). Independent models (models 2 and 3) were constructed for SB and PA. After controlling for sleep quality, SB measure demonstrated a significant positive association with CPM30sec response, but not the PA variable (Table 4).
After controlling for variables (pain severity, pain medication intake before the test session, and PCS—helplessness), neither PA nor SB measures demonstrated associations with CPM60sec response (model 5). Independent models (6 and 7) were constructed for SB and PA against CPM60sec response. In the model 6, after controlling for variables, SB measure demonstrated a significant positive association with CPM60sec response (model 6). However, in model 7, after controlling for variables, PA was not associated with CPM60sec. However, in the backward multivariate model (model 8), SB and pain medication intake before the test session remained in the model, and both demonstrated significant positive associations with CPM60sec response. Pain interference and PSE were not included in the model to avoid multicollinearity with pain severity and PA variables (Table 4).
Multiple linear regression analysis was not conducted for CPM90sec due to nonsignificant relationships between PA/SB variables and CPM90sec percentage change scores (Table 3).
Significant positive relationships were shown between MTS-S and pain severity and interference scores. Similarly, MTS-R scores were positively correlated with pain interference, but not with pain severity scores. Pain severity, interference scores, and psychological factors (PCS, CPAQ, depression, anxiety, CSI, and PSE scores) were positively associated with both MTS-S and MTS-R change scores. However, the number of painful joints, PVAQ, and stress subscale scores were related to MTS-R change scores only. SQcat demonstrated a negative association trend with MTS-S change scores, whereas PSE scores showed a negative association trend with both MTS-S MTS-R change scores (Tables 2 and 3).
No significant correlations were demonstrated between both MTS-S and MTS-R and any of the PA or SB measures (Table 3); hence, a multivariate analysis was not conducted.
This study demonstrated that the individuals who spent a longer duration in a day engaging in SB had a greater CPM effect. Also, PA levels were negatively correlated with the CPM effect. We did not find evidence of a relationship between MTS of pain and SB/PA levels.
Sedentary behaviour levels were associated with greater CPM effects, independent of total time spent in moderate or vigorous physical activities. Also, a significant positive CPM effect (moderate effect size) was demonstrated. These findings are in contrary to the previous studies measuring CPM effect, where greater CPM responses were seen in healthy individuals: who engaged in higher levels of PA and had lower levels of sedentary time; performed better in endurance exercise; and participated in vigorous activities.22,51,52 Generally, these studies included young and older healthy adults, used different QST paradigms, studied different domains of PA, and measured PA using self-report and objective methods.18,19,22,51,52,57,87
Another potential factor that might have contributed to the observed relationship was the participant's PA pattern (unmeasured variable) before the study period. Notably, individuals with chronic pain generally display behavioural patterns in engagement with PA, classically defined as “boom” and “bust” phases of the chronic pain experience cycle.14,49 Anecdotal evidence suggests that people in pain “flare-ups” after engagement in high levels of activity often reduce their activity levels or even engage in SB. It could be speculated that the participants' SB might have induced transient better pain modulatory effects to protect against pain flare-ups, thus explaining the positive cross-sectional relationship between SB and CPM effect in this study.
Although significant negative associations were observed between MTS and PA/SB measures in the pain-free control population,51,52 this study failed to find such associations. Similar to this study, a recent study demonstrated no relationships between moderate or vigorous PA levels and heat-evoked TS of pain in a group of individuals with low back pain.59 Lack of null relationships between MTS and PA/SB measures in this study can be due to observations: lower and skewed MTS change score at the symptomatic site (mean [SD]: 1.9 [1.8]); skewed PA data; inter-regional TS differences (lower scores—neck/shoulder regions vs higher scores at low back/knee/hip regions); higher MTS-S scores in older adults group (vs <65 years); and higher MTS at the painful site (vs remote site). Besides, there is some evidence demonstrating hypoesthesia in the painful region and no signs of CS,30,35 which may have influenced the TS responses in the symptomatic region. Other TS mechanisms such as local tissue responses80 and cognitive and affective responses (perceived threat) to the repeated sensory input can also explain the observed null relationships.11,28 This perceptual component is supported by our data showing significant positive correlations between MTS scores, PCS scores, and pain severity/interference.8,16,65,66 Thus, peripheral mechanisms of TS and perceptions might have confounded the relationship between PA/SB and MTS scores.
This is the first study exploring the role of PA and SB on CPM effect and TS responses in a group of individuals with mixed persistent musculoskeletal pain. This study attempted to adjust known confounding factors in the analysis. Our study participants were free of cognitive impairments, thus minimizing the possibility of recall issues in reporting pain and PA levels. This study used the CPM protocol where the test stimulus was administered at the symptomatic joint against a standard research practice where test stimulus delivered at a remote site. Although CPM effect can be independent of the testing site, it is suggested that measuring CPM response at the most painful location might be more relevant and generalizable for clinical populations, where the original nociceptive drive exists potentially confounding the CPM response assessed at the most painful site. However, this proposition needs further exploration to identify any differences in CPM response (painful vs remote location) and its correlations with pain severity and functional outcomes.
This study has some limitations which include cross-sectional study design, community-based convenience sampling technique75 introducing sampling bias, self-report measures of PA and SB, and smaller sample size, however, similar to previous studies in healthy adults. Because it is a single-group observational study, assessor blinding was not performed; however, it is considered a limitation. There are a few limitations associated with the CPM protocol used in this study. They include noncirculation of cold water, and the pain rating was not recorded following removal. Although the water temperature (12°) used in this study can be considered higher (vs other studies), the similar temperature was used in previous studies that have had induced significant conditioning response.26,37 In contrary to a previous study,51 positive CPM effect was observed, possibly explained by the mixed sample (older and middle-aged adults) of participants and suprathreshold pain (PPT-P4) used as a criterion for test stimulus in this study. Another potential limitation was towards the application of conditioning stimuli at the same segmental level (ie, cold bath immersion of the hand) in participants with shoulders and neck pain (n = 16).98 Therefore, the role of segmental inhibition cannot be ruled out in the CPM response in this study. A percent change of suprathreshold (pain4) PPT scores was used in the statistical analysis to overcome the regional variability in PPT scores. However, the effect of the testing site (varied symptomatic regions) on the observed relationships cannot be entirely ruled out. A possibility of variance inflation due to multicollinearity between independent variables (PA and SB) was ruled out through meeting the statistical indices' criteria (variance inflation factor and tolerance) of the multiple regression modelling.
Prospective longitudinal research should use objective methods for measuring PA and SB patterns and their impact on pain modulatory mechanisms.51 Future research should explore the role of contexts, cognitive, affective factors (eg, fear of movement), and social factors in PA/SB engagement and their impact on pain modulatory systems.1,38,45,91 For example, structured PA, as opposed to leisure-based PA, may have differential effects on pain modulatory functions, mediated through cognitive, emotional, and social factors. Future research should consider measuring washout effects of a conditioning stimulus.37 Moved evoked pain paradigms such as “sensitivity to physical activity” or similar can be used in addition to experimental QST paradigms.12,93 Future studies could use a criterion (ie, at least >2 points on an NPRS for defining a clinically meaningful summation of pain) to categorize the MTS data and assess the relationship.64 Future research should investigate ethnic differences in CPM/MTS responses25 and differences in older adults with multisite joint pain (>50% in this study cohort) vs widespread pain syndromes (fibromyalgia).15,88
Sedentariness, independent of PA levels, is associated with greater CPM effect in people with chronic musculoskeletal pain. Both SB and PA levels were not related to mechanical TS. These findings collectively provide insights on mechanistic processes between PA behaviour and central nociceptive facilitation and inhibition in a symptomatic population. The study findings need to be interpreted with caution due to cross-sectional data and data sourced from a range of patients presenting with different regional pain presentations. Prospective longitudinal studies using objective measures of PA and SB are required to validate these observed relationships in a larger sample size, exploring relationships between PA characteristics, pain modulatory mechanisms, and clinical outcomes.
The authors have no conflict of interest to declare.
This study was funded by the Otago Medical Research Foundation, Jack Thompson Arthritis Research Grant.
. Alschuler KN, Hoodin F, Murphy SL, Rice J, Geisser ME. Factors contributing to physical activity
in a chronic low back pain clinical sample: a comprehensive analysis using continuous ambulatory monitoring. PAIN 2011;152:2521–7.
. Arendt-Nielsen L. Central sensitization in humans: assessment and pharmacology. Handb Exp Pharmacol 2015;227:79–102.
. Backonja MM, Attal N, Baron R, Bouhassira D, Drangholt M, Dyck PJ, Edwards RR, Freeman R, Gracely R, Haanpaa MH, Hansson P, Hatem SM, Krumova EK, Jensen TS, Maier C, Mick G, Rice AS, Rolke R, Treede RD, Serra J, Toelle T, Tugnoli V, Walk D, Walalce MS, Ware M, Yarnitsky D, Ziegler D. Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus. PAIN 2013;154:1807–19.
. Bobinski F, Ferreira TAA, Cordova MM, Dombrowski PA, da Cunha C, Santo CCD, Poli A, Pires RGW, Martins-Silva C, Sluka KA, Santos ARS. Role of brainstem serotonin in analgesia produced by low-intensity exercise on neuropathic pain after sciatic nerve injury in mice. PAIN 2015;156:2595–606.
. Bulls HW, Lynch MK, Petrov ME, Gossett EW, Owens MA, Terry SC, Wesson-Sides KM, Goodin BR. Depressive symptoms and sleep efficiency sequentially mediate racial differences in temporal summation
of mechanical pain. Ann Behav Med 2017;51:673–82.
. Campbell CM, Buenaver LF, Finan P, Bounds SC, Redding M, McCauley L, Robinson M, Edwards RR, Smith MT. Sleep, pain catastrophizing, and central sensitization in knee osteoarthritis patients with and without insomnia. Arthritis Care Res 2015;67:1387–96.
. Carpenter JS, Andrykowski MA. Psychometric evaluation of the Pittsburgh Sleep Quality Index. J Psychosom Res 1998;45:5–13.
. Carriere JS, Martel MO, Meints SM, Cornelius MC, Edwards RR. What do you expect? Catastrophizing mediates associations between expectancies and pain-facilitatory processes. Eur J Pain 2019;23:800–11.
. Chalaye P, Devoize L, Lafrenaye S, Dallel R, Marchand S. Cardiovascular influences on conditioned pain modulation
. PAIN 2013;154:1377–82.
. Cheng HL. A simple, easy-to-use spreadsheet for automatic scoring of the International Physical Activity
Questionnaire (IPAQ) short form. ResearchGate, 2016. doi: .
. Cheng JC, Erpelding N, Kucyi A, DeSouza DD, Davis KD. Individual differences in temporal summation
of pain reflect pronociceptive and antinociceptive brain structure and function. J Neurosci 2015;35:9689–700.
. Corbett DB, Simon CB, Manini TM, George SZ, Riley JL III, Fillingim RB. Movement-evoked pain: transforming the way we understand and measure pain. PAIN 2019;160:757–61.
. Curatolo M, Arendt-Nielsen L. Central hypersensitivity in chronic musculoskeletal pain. Phys Med Rehabil Clin N Am 2015;26:175–84.
. Daenen L, Varkey E, Kellmann M, Nijs J. Exercise, not to exercise, or how to exercise in patients with chronic pain? Applying science to practice. Clin J Pain 2015;31:108–14.
. de Luca K, Wong A, Eklund A, Fernandez M, Byles J, Ferreira M, Parkinson L, Hartvigsen J. Predictors of multi-site joint pain in older Australian women. Osteoarthritis Cartilage 2018;26:S216.
. Edwards RR, Smith MT, Stonerock G, Haythornthwaite JA. Pain-related catastrophizing in healthy women is associated with greater temporal summation
of and reduced habituation to thermal pain. Clin J Pain 2006;22:730–7.
. Fingleton C, Smart K, Moloney N, Fullen BM, Doody C. Pain sensitization in people with knee osteoarthritis: a systematic review and meta-analysis. Osteoarthritis Cartilage 2015;23:1043–56.
. Flood A, Waddington G, Cathcart S. Examining the relationship between endogenous pain modulation
capacity and endurance exercise performance. Res Sports Med 2017;25:300–12.
. Flood A, Waddington G, Thompson K, Cathcart S. Increased conditioned pain modulation
in athletes. J Sports Sci 2017;35:1066–72.
. Freynhagen R, Tolle TR, Gockel U, Baron R. The painDETECT project—far more than a screening tool on neuropathic pain. Curr Med Res Opin 2016;32:1033–57.
. Geneen LJ, Moore RA, Clarke C, Martin D, Colvin LA, Smith BH. Physical activity
and exercise for chronic pain in adults: an overview of Cochrane Reviews. Cochrane Database Syst Rev 2017:CD011279.
. Geva N, Defrin R. Enhanced pain modulation
among triathletes: a possible explanation for their exceptional capabilities. PAIN 2013;154:2317–23.
. Geva N, Pruessner J, Defrin R. Triathletes lose their advantageous pain modulation
under acute psychosocial stress. Med Sci Sports Exerc 2017;49:333–41.
. Goodin BR, Bulls HW, Herbert MS, Schmidt J, King CD, Glover TL, Sotolongo A, Sibille KT, Cruz-Almeida Y, Staud R, Fessler BJ, Redden DT, Bradley LA, Fillingim RB. Temporal summation
of pain as a prospective predictor of clinical pain severity in adults aged 45 years and older with knee osteoarthritis: ethnic differences. Psychosom Med 2014;76:302–10.
. Goodin BR, Kronfli T, King CD, Glover TL, Sibille K, Fillingim RB. Testing the relation between dispositional optimism and conditioned pain modulation
: does ethnicity matter? J Behav Med 2013;36:165–74.
. Granot M, Weissman-Fogel I, Crispel Y, Pud D, Granovsky Y, Sprecher E, Yarnitsky D. Determinants of endogenous analgesia magnitude in a diffuse noxious inhibitory control (DNIC) paradigm: do conditioning stimulus painfulness, gender and personality variables matter? PAIN 2008;136:142–9.
. Grashorn W, Sprenger C, Forkmann K, Wrobel N, Bingel U. Age-dependent decline of endogenous pain control: exploring the effect of expectation and depression. PLoS One 2013;8:e75629.
. Grinberg K, Granot M, Lowenstein L, Abramov L, Weissman-Fogel I. Negative illness perceptions are associated with a pronociceptive modulation profile and augmented pelvic pain. Clin J Pain 2018;34:1141–8.
. Grone E, Crispin A, Fleckenstein J, Irnich D, Treede RD, Lang PM. Test order of quantitative sensory testing facilitates mechanical hyperalgesia in healthy volunteers. J Pain 2012;13:73–80.
. Haik MN, Evans K, Smith A, Henriquez L, Bisset L. People with musculoskeletal shoulder pain demonstrate no signs of altered pain processing. Musculoskelet Sci Pract 2019;39:32–8.
. Heneweer H, Vanhees L, Picavet HS. Physical activity
and low back pain: a U-shaped relation? PAIN 2009;143:21–5.
. Hübscher M, Moloney N, Leaver A, Rebbeck T, McAuley JH, Refshauge KM. Relationship between quantitative sensory testing and pain or disability in people with spinal pain—a systematic review and meta-analysis. PAIN 2013;154:1497–504.
. Huijnen IP, Verbunt JA, Peters ML, Delespaul P, Kindermans HP, Roelofs J, Goossens M, Seelen HA. Do depression and pain intensity interfere with physical activity
in daily life in patients with Chronic Low Back Pain? PAIN 2010;150:161–6.
. Huijnen IPJ, Verbunt JA, Peters ML, Seelen HAM. Is physical functioning influenced by activity-related pain prediction and fear of movement in patients with subacute low back pain? Eur J Pain 2010;14:661–6.
. Kavchak AJ, Fernandez-de-Las-Penas C, Rubin LH, Arendt-Nielsen L, Chmell SJ, Durr RK, Courtney CA. Association between altered somatosensation, pain, and knee stability in patients with severe knee osteoarthrosis. Clin J Pain 2012;28:589–94.
. Keller S, Bann CM, Dodd SL, Schein J, Mendoza TR, Cleeland CS. Validity of the brief pain inventory for use in documenting the outcomes of patients with noncancer pain. Clin J Pain 2004;20:309–18.
. Kennedy DL, Kemp HI, Ridout D, Yarnitsky D, Rice AS. Reliability of conditioned pain modulation
: a systematic review. PAIN 2016;157:2410–19.
. Kim Y, Welk GJ. Characterizing the context of sedentary lifestyles in a representative sample of adults: a cross-sectional study from the physical activity
measurement study project. BMC Public Health 2015;15:1218.
. 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 2011;152:2241–7.
. Landmark T, Romundstad PR, Borchgrevink PC, Kaasa S, Dale O. Longitudinal associations between exercise and pain in the general population—the HUNT pain study. PLoS One 2013;8:e65279
. Law LF, Sluka KA. How does physical activity
modulate pain? PAIN 2017;158:369–70.
. Lewis 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.
. Maddison R, Ni Mhurchu C, Jiang Y, Vander Hoorn S, Rodgers A, Lawes CM, Rush E. International Physical Activity
Questionnaire (IPAQ) and New Zealand Physical Activity
Questionnaire (NZPAQ): a doubly labelled water validation. Int J Behav Nutr Phys Act 2007;4:62.
. Marshall S, Kerr J, Carlson J, Cadmus-Bertram L, Patterson R, Wasilenko K, Crist K, Rosenberg D, Natarajan L. Patterns of weekday and weekend sedentary behavior
among older adults
. J Aging Phys Activ 2015;23:534–41.
. May M, Junghaenel DU, Ono M, Stone AA, Schneider S. Ecological momentary assessment methodology in chronic pain research: a systematic review. J Pain 2018;19:699–716.
. Mayer TG, Neblett R, Cohen H, Howard KJ, Choi YH, Williams MJ, Perez Y, Gatchel RJ. The development and psychometric validation of the central sensitization inventory. Pain Pract 2012;12:276–85.
. McCracken LM. “Attention” to pain in persons with chronic pain: a behavioral approach. Behav Ther 1997;28:271–84.
. McWilliams LA, Asmundson GJG. Assessing individual differences in attention to pain: psychometric properties of the Pain Vigilance and Awareness Questionnaire modified for a non-clinical pain sample. Pers Indiv Differ 2001;31:239–46.
. Moseley GL. A pain neuromatrix approach to patients with chronic pain. Man Ther 2003;8:130–40.
. Nahman-Averbuch H, Nir RR, Sprecher E, Yarnitsky D. Psychological factors and conditioned pain modulation
: a meta-analysis. Clin J Pain 2015;32:541–54.
. Naugle KM, Ohlman T, Naugle KE, Riley ZA, Keith NR. Physical activity
behavior predicts endogenous pain modulation
in older adults
. PAIN 2017;158:383–90.
. Naugle KM, Riley JL. Self-reported physical activity
predicts pain inhibitory and facilitatory function. Med Sci Sports Exerc 2014;46:622–9.
. Neblett R, Cohen H, Choi Y, Hartzell MM, Williams M, Mayer TG, Gatchel RJ. The Central Sensitization Inventory (CSI): establishing clinically significant values for identifying central sensitivity syndromes in an outpatient chronic pain sample. J Pain 2013;14:438–45.
. Nicholas MK, McGuire BE, Asghari A. A 2-item short form of the Pain Self-Efficacy Questionnaire: development and psychometric evaluation of PSEQ-2. J Pain 2015;16:153–63.
. Nijs J, Kosek E, Van Oosterwijck J, Meeus M. Dysfunctional endogenous analgesia during exercise in patients with chronic pain: to exercise or not to exercise? Pain Phys 2012;15(3 suppl):ES205–213.
. Nir RR, Yarnitsky D. Conditioned pain modulation
. Curr Opin Support Palliat Care 2015;9:131–7.
. Ohlman T, Miller L, Naugle KE, Naugle KM. Physical activity
levels predict exercise-induced hypoalgesia in older adults
. Med Sci Sports Exerc 2018;50:2101–9.
. Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 1971;9:97–113.
. Orr LC, George SZ, Simon CB. Association between physical activity
and pain processing in adults with chronic low back pain compared to pain-free controls. J Back Musculoskelet 2017;30:575–81.
. Perneger TV. What's wrong with Bonferroni adjustments. Br Med J 1998;316:1236–8.
. Pottie K, Rahal R, Jaramillo A, Birtwhistle R, Thombs BD, Singh H, Connor Gorber S, Dunfield L, Shane A, Bacchus M, Bell N, Tonelli M; Canadian Task Force on Preventive Health C. Recommendations on screening for cognitive impairment in older adults
. CMAJ 2016;188:37–46.
. Price DD. Characteristics of second pain and flexion reflexes indicative of prolonged central summation. Exp Neurol 1972;37:371–+.
. Quartana PJ, Campbell CM, Edwards RR. Pain catastrophizing: a critical review. Expert Rev Neurother 2009;9:745–58.
. Rabey M, Slater H, O'Sullivan P, Beales D, Smith A. Somatosensory nociceptive characteristics differentiate subgroups in people with chronic low back pain: a cluster analysis. PAIN 2015;156:1874–84.
. Rhudy JL, Lannon EW, Kuhn BL, Palit S, Payne MF, Sturycz CA, Hellman N, Guereca YM, Toledo TA, Coleman HB, Thompson KA, Fisher JM, Herbig SP, Barnoski KB, Chee L, Shadlow JO. Sensory, affective, and catastrophizing reactions to multiple stimulus modalities: results from the Oklahoma study of native American pain risk. J Pain 2019. doi: . [Epub ahead of print].
. Rhudy JL, Martin SL, Terry EL, France CR, Bartley EJ, DelVentura JL, Kerr KL. Pain catastrophizing is related to temporal summation
of pain but not temporal summation
of the nociceptive flexion reflex. PAIN 2011;152:794–801.
. Roelofs J, Peters ML, McCracken L, Vlaeyen JWS. The pain vigilance and awareness questionnaire (PVAQ): further psychometric evaluation in fibromyalgia and other chronic pain syndromes. PAIN 2003;101:299–306.
. Rolke R, Baron R, Maier C, Tolle TR, Treede RD, Beyer A, Binder A, Birbaumer N, Birklein F, Botefur IC, Braune S, Flor H, Huge V, Klug R, Landwehrmeyer GB, Magerl W, Maihofner C, Rolko C, Schaub C, Scherens A, Sprenger T, Valet M, Wasserka B. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. PAIN 2006;123:231–43.
. Rosenberg DE, Norman GJ, Wagner N, Patrick K, Calfas KJ, Sallis JF. Reliability and validity of the Sedentary Behavior
Questionnaire (SBQ) for adults. J Phys Act Health 2010;7:697–705.
. Rosenthal R, Cooper H, Hedges L. Parametric measures of effect size. The handbook of research synthesis. New York, NY, US: Russell Sage Foundation, Vol. 621, 1994. pp. 231–244.
. Roussel NA, Nijs J, Meeus M, Mylius V, Fayt C, Oostendorp R. Central sensitization and altered central pain processing in chronic low back pain: fact or myth? Clin J Pain 2013;29:625–38.
. Sanchis MN, Lluch E, Nijs J, Struyf F, Kangasperko M. The role of central sensitization in shoulder pain: a systematic literature review. Semin Arthritis Rheum 2015;44:710–16.
. Schneiders AG, Sullivan SJ, O'Malley KJ, Clarke SV, Knappstein SA, Taylor LJ. A valid and reliable clinical determination of footedness. PM R 2010;2:835–41.
. Schrimpf M, Liegl G, Boeckle M, Leitner A, Geisler P, Pieh C. The effect of sleep deprivation on pain perception in healthy subjects: a meta-analysis. Sleep Med 2015;16:1313–20.
. Sedgwick P. Convenience sampling. Br Med J 2013;347:f6304.
. Semplonius T, Willoughby T. Long-term links between physical activity
and sleep quality. Med Sci Sports Exerc 2018;50:2418–24.
. Severeijns R, Vlaeyen JWS, van den Hout MA, Weber WEJ. Pain catastrophizing predicts pain intensity, disability, and psychological distress independent of the level of physical impairment. Clin J Pain 2001;17:165–72.
. Sluka KA, O'Donnell JM, Danielson J, Rasmussen LA. Regular physical activity
prevents development of chronic pain and activation of central neurons. J Appl Physiol 2013;114:725–33.
. Stagg NJ, Mata HP, Ibrahim MM, Henriksen EJ, Porreca F, Vanderah TW, Malan TP. Regular exercise reverses sensory hypersensitivity in a rat neuropathic pain model role of endogenous opioids. Anesthesiology 2011;114:940–8.
. Staud R. Peripheral pain mechanisms
in chronic widespread pain. Best Pract Res Clin Rheumatol 2011;25:155–64.
. Staud R. Abnormal endogenous pain modulation
is a shared characteristic of many chronic pain conditions. Expert Rev Neurother 2012;12:577–85.
. Staud R. The important role of CNS facilitation and inhibition for chronic pain. Int J Clin Rheumtol 2013;8:639–46.
. Staud R, Robinson ME, Price DD. Temporal summation
of second pain and its maintenance are useful for characterizing widespread central Sensitization of fibromyalgia patients. J Pain 2007;8:893–901.
. Sullivan MJL, Bishop SR, Pivik J. The Pain Catastrophizing Scale: development and validation. Psychol Assess 1995;7:524–32.
. Suokas AK, Walsh DA, McWilliams DF, Condon L, Moreton B, Wylde V, Arendt-Nielsen L, Zhang W. Quantitative sensory testing in painful osteoarthritis: a systematic review and meta-analysis. Osteoarthritis Cartilage 2012;20:1075–85.
. Tesarz J, Gerhardt A, Schommer K, Treede RD, Eich W. Alterations in endogenous pain modulation
in endurance athletes: an experimental study using quantitative sensory testing and the cold-pressor task. PAIN 2013;154:1022–9.
. Tesarz J, Schuster AK, Hartmann M, Gerhardt A, Eich W. Pain perception in athletes compared to normally active controls: a systematic review with meta-analysis. PAIN 2012;153:1253–62.
. Thapa S, Shmerling RH, Bean JF, Cai Y, Leveille SG. Chronic multisite pain: evaluation of a new geriatric syndrome. Aging Clin Exp Res 2018; 25:1–9.
. Treede RD, Rief W, Barke A, Aziz Q, Bennett MI, Benoliel R, Cohen M, Evers S, Finnerup NB, First MB, Giamberardino MA, Kaasa S, Kosek E, Lavand'homme P, Nicholas M, Perrot S, Scholz J, Schug S, Smith BH, Svensson P, Vlaeyen JWS, Wang SJ. A classification of chronic pain for ICD-11. PAIN 2015;156:1003–7.
. Vierck CJ, Cannon RL, Fry G, Maixner W, Whitsel BL. Characteristics of temporal summation
of second pain sensations elicited by brief contact of glabrous skin by a preheated thermode. J Neurophysiol 1997;78:992–1002.
. Welk GJ, Kim Y. Context of physical activity
in a representative sample of adults. Med Sci Sports Exerc 2015;47:2102–10.
. White KP, Harth M, Speechley M, Ostbye T. Testing an instrument to screen for fibromyalgia syndrome in general population studies: the London Fibromyalgia Epidemiology Study Screening Questionnaire. J Rheumatol 1999;26:880–4.
. Wideman TH, Finan PH, Edwards RR, Quartana PJ, Buenaver LF, Haythornthwaite JA, Smith MT. Increased sensitivity to physical activity
among individuals with knee osteoarthritis: relation to pain outcomes, psychological factors, and responses to quantitative sensory testing. PAIN 2014;155:703–11.
. Wood BM, Nicholas MK, Blyth F, Asghari A, Gibson S. The utility of the short version of the Depression Anxiety Stress Scales (DASS-21) in elderly patients with persistent pain: does age make a difference? Pain Med 2010;11:1780–90.
. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. PAIN 2011;152(suppl 3):S2–S15.
. Yarnitsky D. Conditioned pain modulation
(the diffuse noxious inhibitory control-like effect): its relevance for acute and chronic pain states. Curr Opin Anaesthesiol 2010;23:611–15.
. Yarnitsky D, Arendt-Nielsen L, Bouhassira D, Edwards RR, Fillingim RB, Granot M, Hansson P, Lautenbacher S, Marchand S, Wilder-Smith O. Recommendations on terminology and practice of psychophysical DNIC testing. Eur J Pain 2010;14:339.
. Yarnitsky D, Bouhassira D, Drewes AM, Fillingim RB, Granot M, Hansson P, Landau R, Marchand S, Matre D, Nilsen KB, Stubhaug A, Treede RD, Wilder-Smith OH. Recommendations on practice of conditioned pain modulation
(CPM) testing. Eur J Pain 2015;19:805–6.