Physical exercise and chronic pain in university students.

BACKGROUND: Physical inactivity and chronic pain are both major public health concerns worldwide. Although the health benefits of regular physical exercise are well-documented, few large epidemiological studies have investigated the association between specific domains of physical exercise and chronic pain in young adults. We sought to investigate the association between frequency, intensity and duration of physical exercise, and chronic pain.
METHODS: Data stem from the SHoT2018-study, a national health survey for higher education in Norway, in which 36,625 fulltime students aged 18-35 years completed all relevant questionnaires. Chronic pain, defined according to the International Classification of Diseases 11th Revision (ICD-11), was assessed with a newly developed hierarchical digital instrument for reporting both distribution and characteristics of pain in predefined body regions. Physical exercise was assessed using three sets of questions, measuring the number of times exercising each week, and the average intensity and the number of hours each time.
RESULTS: The majority (54%) of the students reported chronic pain in at least one location, and the prevalence was especially high among women. The overall pattern was an inverse dose-response association between exercise and chronic pain: the more frequent, harder or longer the physical exercise, the lower the risk of chronic pain. Similar findings were generally also observed for the number of pain locations: frequent exercise was associated with fewer pain locations. Adjusting for demographical, lifestyle factors and depression had little effect on the magnitude of the associations.
CONCLUSION: Given the many health benefits of regular exercise, there is much to be gained in facilitating college and university students to be more physically active, ideally, thru a joint responsibility between political and educational institutions. Due to the cross-sectional nature of the study, one should be careful to draw a firm conclusion about the direction of causality.

Introduction

Chronic pain is a major public health concern worldwide, with significant impact on both an individual and a socioeconomic level. While prevalence estimates vary, reviews suggest that chronic pain affects about one-third of the general population [1, 2], and pain was recently highlighted as one of the leading causes of disability by the Global Burden of Disease (GBD) study [3].

Individual variations, including expectations and sensitization [4] caused by a complex interplay between genetic and environmental factor, influence the experience of pain [5]. There is some evidence suggesting a link between a physical inactivity and the development of chronic pain [6, 7]. Several population-based studies have indicated that physical exercise may indeed reduce the risk of chronic pain [8-10]. However, the literature in this field remains mixed, with conflicting evidence regarding a possible association between leisure-time physical activity and pain in the general population [11, 12]. Moreover, most studies in this field are in samples of middle-aged and older adults, with less knowledge about this possible link in younger adults. On the one hand, students pursuing higher education are generally in good health, and many universities try to facilitate their students to be physically active. On the other hand, college and university students may also be prone to inactivity, as many spend up to 10 hours a day in environments characterized by prolonged sitting [13].

Recent evidence shows that the world´s total physical activity level is on the decline across all age groups [14]. Alongside the large public health burden of chronic pain, and what may be labelled the global obesity epidemic [15], it is particularly important to examine the link between physical exercise and chronic pain in younger samples. This group has the potential to live a healthy life and stay in the workforce for many years ahead.

A challenge with the existing research in this field is the heterogeneity in assessment methods, regarding both operationalizations of physical exercise, as well as chronic pain. This diversity in methodology may lead to inaccurate estimates of both prevalence rates and magnitude of associations [2]. In the current study, we aim to improve on these limitations by employing both a well-validated measure on physical exercise, as well as including a newly developed hierarchical digital instrument for reporting both distribution and characteristics of pain in predefined body regions (the Graphical Index of Pain (GRIP) [16].

In terms of potential mechanisms that may account for the association between physical activity and chronic pain, both demographical factors, including gender [17, 18], ethnicity [19], and socioeconomic status [20], as well as health behaviors (alcohol use [21, 22]), sleep problems [23, 24], and depression [25] have previously shown associations to both exercise and pain in young adulthood. These factors are, therefore, essential to account for when examining the link between exercise and chronic pain.

Based on these considerations, using data from a large national study from 2018 of all Norwegian college and university students, we investigated the level of chronic pain as among male and female students in higher education. We also examined the association between the frequency, intensity and duration of physical exercise, and chronic pain, and if sociodemographic, lifestyle or other health factors could explain any of the observed associations.

Materials and methods

Procedure

The current paper used data from the SHoT2018 study (Students’ Health and Wellbeing Study), a large national survey of students enrolled in higher education in Norway, initiated by the three largest student welfare organizations. The SHoT2018 is a comprehensive survey of several domains of health, quality of life and academic functioning, and was collected electronically through a web-based platform. Details of the study has been published elsewhere [26], but in short, SHoT2018 was conducted between February 6 and April 5, 2018, and invited all fulltime Norwegian students pursuing higher education, both in Norway and abroad. In all, 162,512 students fulfilled the inclusion criteria, of whom 50,054 students completed the online questionnaires, yielding a response rate of 30.8%. After first completing the main SHoT2018 questionnaire, all participating students were redirected to the GRIP questionnaire (described below), which 36,625 (73.2%) completed, yielding an overall 22.5% response rate. During the GRIP data collection, the data server had some downtime due to heavy traffic. This may explain why fewer participants completed the GRIP questionnaire. Validated Norwegian translation (i.e. physical exercise, sleep duration and AUDIT) were used, and questionnaires not previously translated into Norwegian were translated, and then back-translated to the original language (English), to ensure accuracy.

Independent variables

Physical exercise

First, the following brief definition of physical exercise was presented to the students: “With exercise, we mean that you, for example, go for a walk, go skiing, swim or take part in a sport”. Exercise was then assessed using three sets of questions, including the average number of times exercising each week, and the average intensity and average hours each time [27]: 1) “How frequently do you exercise?” (Never, Less than once a week, Once a week, 2–3 times per week, Almost every day); 2) “If you exercise as frequently as once or more times a week: How hard do you push yourself? (I take it easy without breaking into a sweat or losing my breath, I push myself so hard that I lose my breath and break into a sweat, I push myself to near-exhaustion); and 3) “How long does each session last?” (Less than 15 minutes, 15–29 minutes, 30 minutes to 1 hour, More than 1 hour”. This 3-item questionnaire has previously been used in the large population-based Nord-Trøndelag Health Study (HUNT) [27, 28]. In the current study, the response options “Never” and “Less than once a week” were combined for the frequency item, constituting the reference category. For the duration item, the response options “Less than 15 minutes” and “15–29 minutes” were also combined for the same reasons. Detailed information on the physical exercise items in the SHoT2018 study has been published elsewhere [29]. Previous validation studies [27, 28] have demonstrated moderate correlations between these questionnaire items and direct measurement of VO2max during maximal work on a treadmill (r = 0.43[frequency], r = 0.40 [intensity] and r = 0.31 [duration]), with ActiReg [30, 31] (an instrument that measures PA and energy expenditure), and with the International Physical Activity Questionnaire [32].

Dependent variables

The Graphical Index of Pain (GRIP)

GRIP is a hierarchical digital body map designed to assess pain and pain-related characteristics [16]. The instrument consists of 10 first-tier regions (head, neck, left arm, right arm, upper and lower back, left leg, right leg, chest, abdomen, genitals/pelvic floor/urethra/anus) followed by anatomical sites at second-tier (167 loci among men and 168 loci among women). Participants were asked to report pain experienced within the last 4 weeks, omitting brief transient pain. Pain characteristics were reported for each of the marked first-tier regions, i.e. pain duration, episode frequency, episode duration, intensity, how bothersome the pain was, and interference with daily activities and sleep. Women were instructed not to report menstrual pain. Instructions and questions in GRIP were put in Norwegian. Translation to English was made by a certified translator, but back translation is still in process [16].

Chronic pain

The definition of chronic pain was based upon the ICD-11 criteria, with pain persisting or recurring for longer than 3 months [33]. In GRIP, subjects reported the time since first onset of pain. The options were: “Less than 4 weeks”, “1–2 months”, “3–5 months”, “6–11 months”, “1–2 years”, “3–5 years”, “More than 5 years (asked about the age of onset)”. Hence, the chronic pain definition in the present study was pain experienced within the last 4 weeks in at least one of ten first tier loci with ≥3 months duration. For purposes of the present study, the GRIP was used to produce several heat maps to visualize the prevalence and distribution of chronic pain.

Moderate to severe chronic pain

The ICD-11 definition of moderate to severe chronic pain is based on three pain-related parameters [33]: a) pain intensity, b) pain-related distress and c) task interference. The assessment may be graded on a 100-mm visual analogue scale (VAS) (4). The participants in SHoT2018 were asked to grade the following pain characteristics on a VAS (from 0 to 10): a) pain intensity (anchors: No pain/The strongest imaginable pain), b) bothering as a proxy of pain-related distress (anchors: No bother/The greatest imaginable bother), and c) impact on activity in daily activities, as a proxy of task interference (anchors: Not at all /Can’t do anything) (4). We regarded that moderate to severe chronic pain was present in subjects reporting pain within the last 4 weeks in at least one of 10 first tier body regions, with the onset of ≥3 months, and with pain intensity of VAS ≥4, bothering of VAS ≥4, and impact on daily activities of VAS ≥4.

Control variables

Sociodemographic information

All participants reported their gender, age and relationship status (coded as single versus married/partner or girl-/boyfriend). Economic activity was coded dichotomously according to self-reported annual income (before tax and deductions, and not including loans and scholarships): “economically active” (annual income > 10,000 NOK) versus “economically inactive” (≤ 10,000 NOK). Finally, participants were categorized as an immigrant if either the participants or one or both of his/her parents were born outside Norway.

Body Mass Index (BMI)

BMI was calculated based on self-reported body weight (kg) divided by self-reported squared height (m2), and categorized as underweight (BMI < 18.5), normal weight (BMI 18.5–24.9), overweight (BMI 25.0–29.9) and obesity (BMI ≥ 30). Trend data on overweight and obesity from the SHoT studies have been published elsewhere [29].

Sleep duration

The participants’ self-reported usual bedtime and wake up time were indicated in hours and minutes, and data were reported separately for weekdays and weekends. Time in bed (TIB) was calculated as the difference between bedtime and wake up time. Sleep onset latency (SOL) and wake after sleep onset (WASO) were also indicated separately for weekdays and weekends in hours and minutes. Sleep duration was defined as TIB minus SOL and WASO. More detailed information about the sleep inventory in SHoT2018 has been published elsewhere [34].

Alcohol-related problems

Alcohol-related problems were assessed by the Alcohol Use Disorders Identification Test (AUDIT), which is a widely used instrument developed by the World Health Organization to identify risky or harmful alcohol use [35, 36]. The 10-item AUDIT includes items for measuring the frequency, typical amount and episodic heavy drinking frequency (items 1–3), alcohol dependence (items 4–6), and problems related to alcohol consumption (items 7–10) [37]. The AUDIT score ranges from 0 to 40. More information about the AUDIT in the SHoT surveys has been published elsewhere [38].

Depression

Self-reported depressive disorder was assessed from a pre-defined list of several common somatic and mental conditions/disorders adapted to fit this age-cohort. The list was based on a similar operationalization used in previous large population-based studies (the HUNT study [39]) and included several subcategories for most conditions/disorders (not listed here). For mental disorders, the list comprised the following specific disorders/group of disorders: ADHD, anxiety disorder, autism/Asperger, bipolar disorder, depression, PTSD (posttraumatic stress disorder), schizophrenia, personality disorder, eating disorder, Tourette’s syndrome, obsessive-compulsive disorder (OCD), and other. The list contained no definition of the included disorders/conditions. In the current study, only depressive disorder was included.

Statistical analyses

The heat maps were created in R (version 3.6.1; https://www.r-project.org) with functions to create vector graphics to color loci of the GRIP images, based on values in the input data matrix. IBM SPSS Statistics 25 for Windows (SPSS Inc., Chicago, IL) was used for the other analyses. Pearson’s chi-squared tests were used to examine differences in the prevalence of pain by physical exercise level, stratified by gender. Logistic regression models were computed to obtain effect-size estimates for the dichotomous dependent variables. Results are presented as odds-ratios (ORs) with 95% confidence intervals. We computed one unadjusted and two adjusted models. In the first block we controlled for socio-demographic factors (categorical), body-mass index (continuous), alcohol use and problems (AUDIT continuous sum score), and sleep duration (continuous). In the second block (fully adjusted model) we additionally adjusted for self-reported depression. Estimated marginal means (EMM) were also computed to examine exercise frequency against number of pain loci, adjusting for age. Missing values were handled using listwise deletion.

Ethics

All procedures involving human subjects/patients were approved by the Regional Committee for Medical and Health Research Ethics in Western Norway (no. 2017/1176 [SHOT2018]). Electronic informed consent was obtained after the participants had received a detailed introduction to the study.

Results

Sample characteristics

In all, 36625 students (67.2% women [n = 24600] and 32.8% men [n = 12025]) with a mean age of 23.2 years, completed both the main SHOT2018 questionnaire and the additional GRIP instrument. Approximately half of the students were single, 87% had no additional income besides students’ loan and scholarships, while 8% were of non-Norwegian ethnicity. More details of sociodemographic and clinical characteristics are listed in Table 1.

Table 1

Sociodemographic and clinical characteristics of the study sample.

	Women		Men			Total sample
	mean / n	SD / %	mean / n	SD / %	p-value§	mean / n	SD / %
Age, mean (SD)	23.2	(3.3)	23.6	(3.3)	< .001	23.2	(3.3)
Marital status, n (%)					< .001
Single	13004	(52.9%)	5323	(44.3%)		18327	(50.1%)
Married/partner/girl- or boyfriend	11570	(47.1%)	6683	(55.7%)		18253	(49.9%)
Immigrant status, n (%)					.292
Ethnic Norwegian	22644	(92.0%)	11056	(91.9%)		33700	(92.0%)
Immigrant	1956	(8.0%)	969	(8.1%)		2925	(8.0%)
Economic activity, n (%)					< .001
Active	2836	(12.0%)	1874	(15.9%)		4710	(13.3%)
Inactive	20843	(88.0%)	9894	(84.1%)		30737	(86.7%)
Body-mass index category, n (%)
Underweight	973	(4.1%)	424	(2.1%)		1215	(3.4%)
Normal weight	15604	(65.5%)	7234	(61.6%)		22838	(64.2%)
Overweight	5054	(21.2%)	3355	(28.6%)		8409	(23.7%)
Obese	2189	(9.2%)	7904	7.7%)		3090	(8.7%)
Sleep duration, mean (SD)	7:26	(1:24)	7:24	(1:24)	.047	7:25	(1:24)
AUDIT sum score, mean (SD)	6.7	(4.4)	8.1	(5.1)	< .001	7.3	(4.7)
Depression, n (%)	2943	(12.0%)	912	(7.6%)	< .001	3855	(10.5%)
ICD-11 Chronic pain, # body regions, n (%)					< .001
None	9854	(40.1%)	6914	(57.5%)		16768	(45.8%)
1 body region	4900	(19.9%)	2355	(19.6%)		7255	(19.8%)
2 body regions	4118	(16.7%)	1473	(12.2%)		5591	(15.3%)
3 or more body regions	5728	(23.3%)	1283	(10.7%)		7011	(19.1%)
ICD-11 Chronic pain moderate to severe, # body regions, n (%)					< .001
None	19894	(80.9%)	11172	(92.9%)		31066	(84.8%)
1 body region	1846	(7.5%)	434	(3.6%)		2280	(6.2%)
2 body regions	1263	(5.1%)	235	(2.0%)		1498	(4.1%)
3 or more body regions	1597	(6.5%)	184	(1.5%)		1781	(4.9%)

§ p-values based on overall Chi-squared analyses (categorical variables) or independent samples t-test (continuous variables)

Physical exercise and chronic pain

About half (54.2%) of students reported at least one chronic pain location. Nearly one in five students (19.1%) reported three or more chronic pain locations. There were large gender differences in the prevalence of pain, with female students reporting significantly more pain compared to the male students (Table 1). Fig 1 shows the prevalence and distribution of chronic pain stratified by the average weekly frequency of physical exercise in men and women. There was an inverse dose-response association between exercise frequency and chronic pain: the more frequent exercise, the less chronic pain. Table 2 provides more details of the association between the three exercise items (frequency, intensity, duration) and chronic pain stratified by gender. Compared to exercising never or less than once a week, female students who exercised almost every day were 23% less likely (OR = 0.77) to have chronic pain. Adjusting for potential demographical and clinical confounders only slightly attenuated this association (OR = 0.85, 95% CI: 0.77–0.83). Similarly, exercising 2–3 times per week and once a week decreased the odds of chronic pain compared to exercising less than once a week (Table 2). In terms of the intensity of the physical exercise among females, there were no clear or strong trends regarding the odds of chronic pain. In contrast, the duration of the exercise was inversely associated with reporting more pain: female students exercising more than 1 hour a week were around 20% less likely to report chronic pain compared to students exercising hour less than 30 minutes a week (fully adj. OR = 0.83, 95% CI: 0.75–0.92).

Fig 1

Prevalence and distribution of chronic pain by the average weekly frequency of physical exercise in men and women.

Table 2

Association between physical exercise and chronic pain in male and female university and college and university students.

	ICD-11 chronic pain
			Unadjusted model		Adjusted model§		Fully adjusted model#
	n	(%)	OR	95% CI	OR	95% CI	OR	95% CI
Women
Physical exercise (frequency)
Never/less than once a week	2352	(63.5)	1.00		1.00		1.00
Once a week	2501	(61.7)	0.92	(0.83–1.01)	0.94	(0.85–1.04)	0.96	(0.90–1.00)
2–3 times per week	6719	(59.6)	0.85	(0.78–0.92)	0.88	(0.81–0.96)	0.92	(0.84–0.99)
Almost every day	3155	(57.2)	0.77	(0.70–0.84)	0.81	(0.74–0.89)	0.85	(0.77–0.93)
Physical exercise (intensity)
I take it easy without breaking into a sweat or losing my breath	2902	(64.2)	1.00		1.00		1.00
I push myself so hard that I lose my breath and break into a sweat	10072	(58.8)	0.79	(0.74–0.85)	0.81	(0.75–0.87)	0.83	(0.77–0.90)
I push myself to near-exhaustion	1200	(61.3)	0.89	(0.80–1.00)	0.89	(0.79–0.99)	0.92	(0.81–1.03)
Physical exercise (duration)
Less than 30 minutes	1774	(64.4)	1.00		1.00		1.00
30 minutes to 1 hour	8034	(59.6)	0.80	(0.72–0.88)	0.81	(0.74–0.89)	0.83	(0.76–0.92)
More than 1 hour	4371	(59.3)	0.78	(0.71–0.86)	0.80	(0.73–0.89)	0.83	(0.75–0.92)
Men
Physical exercise (frequency)
Never/less than once a week	1151	(49.5)	1.00		1.00		1.00
Once a week	758	(44.0)	0.79	(0.69–0.90)	0.81	(0.70–0.92)	0.83	(0.73–0.95)
2–3 times per week	1955	(41.3)	0.70	(0.63–0.78)	0.71	(0.64–0.79)	0.74	(0.66–0.82)
Almost every day	1239	(38.7)	0.63	(0.57–0.71)	0.65	(0.59–0.74)	0.69	(0.61–0.77)
Physical exercise (intensity)
I take it easy without breaking into a sweat or losing my breath	764	(46.6)	1.00		1.00		1.00
I push myself so hard that I lose my breath and break into a sweat	3232	(41.8)	0.82	(0.73–0.92)	0.84	(0.75–0.94)	0.85	(0.76–0.86)
I push myself to near-exhaustion	755	(40.0)	0.75	(0.65–0.86)	0.75	(0.65–0.86)	0.77	(0.67–0.89)
Physical exercise (duration)
Less than 30 minutes	540	(45.3)	1.00		1.00		1.00
30 minutes to 1 hour	2011	(43.5)	0.91	(0.80–1.04)	0.89	(0.78–1.02)	0.92	(0.80–1.05)
More than 1 hour	2200	(40.5)	0.80	(0.70–0.91)	0.80	(0.70–0.92)	0.83	(0.72–0.95)

§ Adjusted for socio demographics, body-mass index, alcohol use and problems and sleep duration

# Additional adjustment for self-reported depression

Similar trends were observed among male students, but the beneficial effects were overall higher (lower ORs) than for females, especially regarding the frequency of physical exercise. In contrast to female students, there was a significant inverse dose-response relationship between exercise intensity and chronic pain among male students. This pattern was also observed for exercise duration; the longer duration of the exercise, the lower odds for chronic pain. Overall, adjusting for the potential confounding factors had little effect on the magnitude of the associations (Table 2).

Physical exercise and moderate to severe chronic pain

When examining the association between the physical exercise items and odds of moderate-to-severe chronic pain, similar patterns and comparable effect-sizes, as for the chronic pain analyses, were observed (Table 3).

Table 3

Association between physical exercise and moderate to severe chronic pain in male and female university and college and university students.

	ICD-11 moderate to severe chronic pain
			Unadjusted model		Adjusted model§		Fully adjusted model#
	n	(%)	OR	95% CI	OR	95% CI	OR	95% CI
Women
Physical exercise (frequency)
Never/less than once a week	858	(23.2)	1.00		1.00		1.00
Once a week	801	(19.8)	0.84	(0.74–0.94)	0.89	(0.79–0.99)	0.91	(0.81–1.03)
2–3 times per week	2124	(18.8)	0.79	(0.71–0.87)	0.85	(0.77–0.94)	0.90	(0.81–0.99)
Almost every day	918	(16.6)	0.67	(0.60–0.75)	0.74	(0.67–0.83)	0.79	(0.70–0.88)
Physical exercise (intensity)
I take it easy without breaking into a sweat or losing my breath	1037	(23.0)	1.00		1.00		1.00
I push myself so hard that I lose my breath and break into a sweat	3043	(17.8)	0.74	(0.68–0.80)	0.76	(0.69–0.82)	0.79	(0.72–0.86)
I push myself to near-exhaustion	413	(21.1)	0.90	(0.79–1.03)	0.91	(0.79–1.04)	0.94	(0.82–1.08)
Physical exercise (duration)
Less than 30 minutes	634	(23.0)	1.00		1.00		1.00
30 minutes to 1 hour	2419	(18.0)	0.74	(0.66–0.82)	0.77	(0.69–0.86)	0.80	(0.72–0.89)
More than 1 hour	1440	(19.5)	0.81	(0.72–0.90)	0.85	(0.76–0.95)	0.89	(0.79–0.99)
Men
Physical exercise (frequency)
Never/less than once a week	227	(9.8)	1.00		1.00		1.00
Once a week	117	(6.8)	0.65	(0.51–0.83)	0.70	(0.55–0.89)	0.73	(0.57–0.93)
2–3 times per week	284	(6.0)	0.57	(0.47–0.69)	0.61	(0.50–0.74)	0.65	(0.53–0.78)
Almost every day	220	(6.9)	0.67	(0.55–0.82)	0.74	(0.60–0.81)	0.79	(0.65–0.98)
Physical exercise (intensity)
I take it easy without breaking into a sweat or losing my breath	141	(8.6)	1.00		1.00		1.00
I push myself so hard that I lose my breath and break into a sweat	508	(6.6)	0.72	(0.59–0.88)	0.77	(0.62–0.94)	0.80	(0.65–0.98)
I push myself to near-exhaustion	133	(7.0)	0.76	(0.59–0.98)	0.79	(0.61–1.03)	0.83	(0.64–1.08)
Physical exercise (duration)
Less than 30 minutes	105	(8.8)	1.00		1.00		1.00
30 minutes to 1 hour	319	(6.9)	0.75	(0.59–0.95)	0.75	(0.59–0.86)	0.79	(0.62–1.00)
More than 1 hour	360	(6.6)	0.70	(0.56–0.89)	0.72	(0.56–0.91)	0.76	(0.60–0.97)

§ Adjusted for socio demographics, body-mass index, alcohol use and problems and sleep duration

# Additional adjustment for self-reported depression

Physical exercise and number of pain locations

In general, women reported more pain locations than men irrespective of responses on the three exercise items. For exercise frequency, there was a clear dose-response association; the more frequent the exercise, the fewer the pain locations. This trend was particularly pronounced for female students (Fig 2—panels 2A and 2B).

Fig 2

Association between physical exercise frequency (top), intensity (middle) and duration (bottom) and number of ICD-11 chronic pain loci (left) and number of ICD-11 moderate to severe chronic pain loci (right) for male (red) and female (green) students at Norwegian colleges and universities.

Boxes represent estimated marginal means (EMM; adjusted for age), and error bars represent 95% confidence intervals.

Women reporting moderate exercise intensity had the least pain locations, compared to the women reporting little or hard exercise intensity. In contrast, exercise intensity was associated with pain location in a dose-response manner among males; the less exercise intensity, the more pain locations (Fig 2—panels 2C and 2D). In terms of exercise duration, students with short exercise durations (<30 minutes) had more pain locations than those exercising either 30 minutes to 60 minutes, or more than one hour a week (Fig 2—panels 2E and 2F).

Discussion

This current study has several noteworthy findings. First, the prevalence of chronic pain was high, especially among women, with more than half of the students reporting at least one chronic pain location. With some gender differences, the overall pattern was an inverse dose-response association between exercise and chronic pain: the more frequent, harder or longer the exercise, the lower the odds of chronic pain. Similar findings were generally also observed for the number of pain locations: frequent exercise was associated with fewer pain locations. Adjusting for demographical, lifestyle factors and depression had little effect on the magnitude of the associations.

The observed prevalence of chronic pain in the current study was even higher than what has been observed in similar studies. In a recent review and meta-analysis of chronic pain in epidemiological studies, a pooled chronic pain prevalence of 31% was reported, although the authors concluded that the lack of consistency in defining chronic pain makes evaluations and comparisons across study populations difficult [2]. A systematic review of previous studies reporting on the link between exercise and low back pain concluded that most studies in this field have failed to find a significant relationship between the two [40]. While this may indeed be the case for low back pain, it has been speculated that significant associations may be concealed due to crude measurements of both pain and exercise, as well as other methodological shortcomings [41]. To our knowledge, only Landmark and colleagues [9], using detailed exercise data from the large HUNT3 study from 2006–2008, have examined the link between frequency, duration, and intensity of recreational exercise and chronic pain. Although the HUNT3 study includes a substantial proportion of older adults (65+ years), subgroup analyses of participants aged 20–64 years revealed a U-shaped association between exercise frequency and chronic pain. In contrast, the current study found this association to be linear; the more frequent the weekly exercise, the lower the risk of chronic pain. There may be several possibilities for these divergent findings, but we cannot disregard the possibility that differences in both sample composition and pain assessment, may play a role. Specifically, the assessment of chronic pain in the current study included a more thorough assessment, compared to the briefer 2-items pain inventory used in the HUNT3 study. Of importance, in a smaller longitudinal follow-up study of 6419 participants in the HUNT-3 study, Landmark et al. [10] found that regular exercise at baseline was associated with less pain over a 12 month follow-up period. However, the relationship was substantially reduced when controlling for baseline pain and was only significant for men. Concluding that the associations were close in time and weak, the Landmark et al. studies show that the significance of the exercise-pain link remains open for discussion. As such, the current national study of young adults, extending on previous evidence by using detailed instruments of both pain and exercise, suggest that there is indeed a significant association, and stronger in magnitude than previously believed, between reduced activity and risk of chronic pain.

The findings from the current study have some important clinical and public health implications. Both sedentary behavior [42] and pain [3] are some of our biggest public health challenges in the general population. The increasing level of inactivity has led the World Health Organization (WHO) to launch a global action plan [43] on physical activity for 2018 to 2030 in an attempt to make the world’s population more active. This action plan aims at providing a system-based framework of effective and practical policy actions to countries in order to increase physical activity at all levels, emphasizing the need for a paradigm shift. Moreover, colleges and universities should to a larger extent, consider facilitating their students to take part in sports and exercise, perhaps also by having physical exercise become more integrated into the college environment.

In terms of future research, there is a need to conduct well-controlled and prospective studies to explore if, or to what extent, we can prevent chronic pain by increasing our level of physical exercise. It is also important to examine this across populations, both in terms of different age cohorts, and in healthy versus clinical samples. As also emphasized by Landmark et al. [10], identifying specific groups that may benefit more from exercise interventions to reduce the risk of chronic pain and improve health in general, would be an important objective for future investigations.

Methodological considerations

The most important limitation of the current study is the cross-sectional nature of the study, limiting our ability to study the directionality between physical exercise and chronic pain. As such, inactivity may be both a risk factor, as well as a consequence of chronic pain. Another important limitation is the modest response rate, with little information about the characteristics of non-participants beyond age and gender distribution. Selective participation could bias the prevalence observed to the extent the selection was correlated with reports of chronic pain. On the one hand, it has been shown that non-participants of health surveys in general have poorer health than participants [44]. The current results may, therefore, represent an underestimation of the true prevalence of chronic pain in the target population. On the other hand, people are in general more prone to participate in a survey if the topic is relevant to them personally [45]. As the information material of the SHoT2018-study focused much on “how the students really are and feel”, one may speculate if this would lead to a higher participation rate of individuals who felt that the topic was of particular relevance to them. Since response rates are particularly important in prevalence studies, care should be taken when generalizing the current findings to the whole student population. Rather, it may be more appropriate to emphasize the relative differences between men and women, as these estimates are less prone to selection bias. Using a web-based survey approach may have contributed to the modest response rate, as electronic platforms have been shown to yield somewhat lower participation rates compared to traditional approaches [46, 47]. However, there are also reports showing similar response rates between online and paper questionnaires [48]. A final limitation related to the self-reported physical activity measure is that it is more accurate to say that we assessed perceived intensity, as less fit individuals will feel exhausted by an intensity that a fit person will feel comfortable.

Strengths of the current study include the large and heterogeneous sample, the use of well-validated instruments, and the inclusion of several potential confounders.

Conclusions

The demonstrated health benefits of regular exercise suggest that facilitating young adults to become more physically active should be a prioritized task both for political and educational institutions.

4 May 2020

PONE-D-20-09746

Physical exercise and chronic pain in university students

PLOS ONE

Dear Prof. Sivertsen,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

I agreed with the reviewers that there is need to strengthen the manuscript by attending to some methodological analytical omissions. Specifically, there is need to include information on the utility and psychometrics of the measurement scales in the studied population, improve clarity on the physical activity continuum (physical inactivity vs sedentary time) and the language of the survey and its administration, It is also very important to reconsider the analytic method or provide strong justification for the current analyses. Why was socioeconomic status and psychological variables (e.g., depression measures or other mental health scales) not adjusted for in the analyses considering these are potential mediators of chronic pain in the Scandinavian?

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Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: I Don't Know

**********

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Reviewer #1: Yes

Reviewer #2: Yes

**********

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Reviewer #1: Yes

Reviewer #2: Yes

**********

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Reviewer #1: Re: comments on the manuscript number “PONE-D-20-09746”.

Importance and objective of the paper

Chronic pain is a major health problem globally. It is highlighted as one of the leading cause of years lived with disability, imposing substantial burdens on individuals and community. Although there are small percent of people develop chronic pain, the treatment for those people are complicated and costly. The beneficial effects of physical activity for many chronic diseases have been well documented. Therefore, I see this article is important as it investigates the association between engaging in different amounts of physical exercise and chronic pain.

Generally, the authors do a good job in describing the problem and research question, detailing the methods and results, and providing contextual information to aid in the interpretation of the results. However, there is room for improvement.

Major comment:

I see that the authors of this study are frequently using passive voice in writing the paper. I think that the passive voice is weak and sometime incorrect. I would suggest using active voice in some sections of the paper.

Minor comments:

INTRODUCTION

1) “In terms of the latter, there is some evidence suggesting a link between a sedentary lifestyle and the development of chronic pain”

I would suggest talking about lower levels of physical activity or inactivity, which is related to your topic, instead of talking about sedentary behavior. “Sedentary behavior is any waking behavior characterized by an energy expenditure ≤1.5 metabolic equivalents (METs), while in a sitting, reclining or lying posture”. Therefore, it is likely for someone to accumulate large amounts of both vigorous physical activity and sedentary behavior in one day. For example, someone may work 8 hours on desk and in the same day he may run or swim for 2 hours.

I would recommend you reading these articles: https://ijbnpa.biomedcentral.com/articles/10.1186/s12966-017-0525-8

https://www.nrcresearchpress.com/doi/10.1139/h2012-024#.XpWFA8gzaUk

I would suggest for you to rewrite this paragraph and focus on studies that measured the association between physical activity levels and pain.

METHODS

1) Procedure

The procedure is confusing me! As I see that you are talking about a different study published in 2018! I was expecting to find some information on the procedures that you followed in your study. I think you need some extra sentences in the beginning of this section before starting to talk about SHoT2018.

2) Physical exercise

“In the current study, the response options “Never” and “Less than once a week” were combined for the frequency item, constituting the reference category.”.

As I see in the results section that the highest physical activity category was set to be the reference category. Therefore, I see conflicted information in this study! Could you clarify that?

I would suggest that you set the lowest physical activity category to be the reference category. It is very important for the readers and researchers to look at whether increasing physical activity is associated with any additional benefits for chronic pain.

3) Sociodemographic information

“economically active” (annual income > 10,000 NOK) versus “economically inactive” (< 10,000 NOK).”

So, what about people who will have income equal to 10,000! They will be categorized as economically active or inactive?

4) Sleep duration

What do you mean with rise time? Do you mean wake time?

RESULTS

1) In general, I suggest for you to set up the lowest category to be the reference category.

2) “Table 1. Sociodemographic and clinical characteristics of the SHoT 2018 study.”

I would suggest for you talking about the data that you used in your study. You could only clarify in the procedure section that you used data from the SHoT2018. Could you do that throughout the manuscript?

3) Physical exercise and chronic pain

I see that in this section that you are sometimes talking about chronic pain intensity and sometimes chronic pain locations! However, when I looked at the table I found “chronic pain” only! Could you be clearer in your writing about this point?

4) Physical exercise and moderate to severe chronic pain

“Also, the ORs for exercise duration and moderate-to-severe chronic pain among males were higher than those found for chronic pain.”

I did not see big differences between them! I would suggest for you to focus on the significant results.

DISCUSSION

1) “This large national health survey from 2018, inviting all Norwegian full-time college and university students in the age 18-35, has several interesting findings.”

It does not make sense to me whether you are talking about your study findings or the survey!

2) “The observed prevalence of chronic pain in the current study was high but comparable to what

has also been observed in similar studies. In a recent review and meta-analysis of chronic pain in

epidemiological studies, a pooled chronic pain prevalence of 31% was reported, although the authors concluded that the lack of consistency in defining chronic pain makes evaluations and comparisons across study populations difficult”.

The prevalence of chronic pain in your study was around 54%! I do not think it is similar to the review that your reported which says 31%!

3) “Strengths of the SHoT study include the very large sample size, in combination with several well-validated questionnaires.”.

I think this sentence is related to the next paragraph!

4) Could you write a conclusion paragraph at the end of the DISCUSSION section?

Reviewer #2: Although this paper is very well written and addresses an important topic, my biggest concern is whether psychological factors and economic factors have been considered as confounders among this group. This group is particularly at risk of depression due to financial issues (not sure if same in Norway as other countries) or family issues, and there is a known link between depression and chronic pain, and if not factored in could have influenced the results. In addition, Scandinavian countries are known for having a high prevalence of depression - due to factors such as weather, etc. Has this been factored in as confounders ? I see you have included economic status, but was this adjusted for as well? No psychological outcomes seem to have been measured.

And then one other issue - in which language where all questionnaires/scales administered? Were those not previously validated and translated, translated and validated at any point among this group in this study? not clear from text, although reference made for certain tools.

**********

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Reviewer #1: Yes: Hosam Alzahrani

Reviewer #2: No

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Submitted filename: renamed_f125d.docx

Click here for additional data file.

20 May 2020

Dear Editor

Thank you for the constructive and positive comments from you and the two reviewers, and our chance to revise and improve our manuscript. As outlined below, we have responded to each of the comments and we have described the changes we have made in the manuscript. We hope you agree that the manuscript has improved through this process, and we are pleased to submit our revised manuscript for your consideration.

EDITOR

I agreed with the reviewers that there is need to strengthen the manuscript by attending to some methodological analytical omissions. Specifically, there is need to include information on the utility and psychometrics of the measurement scales in the studied population, improve clarity on the physical activity continuum (physical inactivity vs sedentary time) and the language of the survey and its administration, It is also very important to reconsider the analytic method or provide strong justification for the current analyses. Why was socioeconomic status and psychological variables (e.g., depression measures or other mental health scales) not adjusted for in the analyses considering these are potential mediators of chronic pain in the Scandinavian?

Response: We agree with these comments, and as outlined in our responses to the reviewers below, we have modified the manuscript to accommodate these issues. Specifically, we now provide more details regarding the psychometrics of the physical exercise questionnaire, and we no longer refer to the term “sedentary behaviors” (rather, we use physical activity or exercise throughout the manuscript. We now also state that all questionnaires in the SHOT2018 were administered in Norwegian, and questionnaires not previously translated into Norwegian were translated, and then back-translated to the original language (English), to ensure accuracy. As also suggested by reviewer #2, we now also control for depression (and income) in the fully adjusted logistic regression analyses.

REVIEWER # 1

Importance and objective of the paper

Chronic pain is a major health problem globally. It is highlighted as one of the leading cause of years lived with disability, imposing substantial burdens on individuals and community. Although there are small percent of people develop chronic pain, the treatment for those people are complicated and costly. The beneficial effects of physical activity for many chronic diseases have been well documented. Therefore, I see this article is important as it investigates the association between engaging in different amounts of physical exercise and chronic pain.

Generally, the authors do a good job in describing the problem and research question, detailing the methods and results, and providing contextual information to aid in the interpretation of the results. However, there is room for improvement.

Major comment:

I see that the authors of this study are frequently using passive voice in writing the paper. I think that the passive voice is weak and sometime incorrect. I would suggest using active voice in some sections of the paper.

Response: We now use more active voice in the manuscript.

Minor comments:

INTRODUCTION

1) “In terms of the latter, there is some evidence suggesting a link between a sedentary lifestyle and the development of chronic pain”

I would suggest talking about lower levels of physical activity or inactivity, which is related to your topic, instead of talking about sedentary behavior. “Sedentary behavior is any waking behavior characterized by an energy expenditure ≤1.5 metabolic equivalents (METs), while in a sitting, reclining or lying posture”. Therefore, it is likely for someone to accumulate large amounts of both vigorous physical activity and sedentary behavior in one day. For example, someone may work 8 hours on desk and in the same day he may run or swim for 2 hours.

I would recommend you reading these articles:

https://ijbnpa.biomedcentral.com/articles/10.1186/s12966-017-0525-8

https://www.nrcresearchpress.com/doi/10.1139/h2012-024#.XpWFA8gzaUk

I would suggest for you to rewrite this paragraph and focus on studies that measured the association between physical activity levels and pain.

Response: We appreciate the reviewer pointing us to these two interesting papers. We have now rewritten the relevant paragraph in the introduction accordingly, no longer using the term sedentary/sedentary behaviors.

METHODS

1) Procedure

The procedure is confusing me! As I see that you are talking about a different study published in 2018! I was expecting to find some information on the procedures that you followed in your study. I think you need some extra sentences in the beginning of this section before starting to talk about SHoT2018.

Response: We agree that this section was not entirely clear with regards to the description of the entire SHoT018 study and the current paper. We have now modified this section to improve clarity.

2) Physical exercise

“In the current study, the response options “Never” and “Less than once a week” were combined for the frequency item, constituting the reference category.”.

As I see in the results section that the highest physical activity category was set to be the reference category. Therefore, I see conflicted information in this study! Could you clarify that?

I would suggest that you set the lowest physical activity category to be the reference category. It is very important for the readers and researchers to look at whether increasing physical activity is associated with any additional benefits for chronic pain.

Response: We appreciate these comments and for pointing out the inconsistencies regarding what is the reference group in the physical exercise measure. As suggested by the reviewer, we now use the lowest level of physical activity as the reference category in order to more clearly show the beneficial/protective effect (shown by OR < 1.0) of increasing exercise on chronic pain. All relevant text and tables have been modified accordingly.

3) Sociodemographic information

“economically active” (annual income > 10,000 NOK) versus “economically inactive” (< 10,000 NOK).”

So, what about people who will have income equal to 10,000! They will be categorized as economically active or inactive?

Response: We have now fixed this error to “economically inactive” (≤ 10,000 NOK).”

4) Sleep duration

What do you mean with rise time? Do you mean wake time?

Response: We now use the term wake up time instead of rise time.

RESULTS

1) In general, I suggest for you to set up the lowest category to be the reference category.

Response: We agree, and this has now been changed throughout the paper.

2) “Table 1. Sociodemographic and clinical characteristics of the SHoT 2018 study.”

I would suggest for you talking about the data that you used in your study. You could only clarify in the procedure section that you used data from the SHoT2018. Could you do that throughout the manuscript?

Response: This has now been changed throughout the manuscript.

3) Physical exercise and chronic pain

I see that in this section that you are sometimes talking about chronic pain intensity and sometimes chronic pain locations! However, when I looked at the table I found “chronic pain” only! Could you be clearer in your writing about this point?

Response: We agree that this terminology here may be somewhat confusing. The term “Chronic pain” (2nd row in Table 2) and ”Moderate to severe chronic pain” ” (2nd row in Table 3) refers to the two ICD-11 definitions of outlined in the instrument section in the Methods. We have now inserted “ICD-11” to these two rows to improve clarity.

4) Physical exercise and moderate to severe chronic pain

“Also, the ORs for exercise duration and moderate-to-severe chronic pain among males were higher than those found for chronic pain.”

I did not see big differences between them! I would suggest for you to focus on the significant results.

Response: True. This sentence has now been deleted.

DISCUSSION

1) “This large national health survey from 2018, inviting all Norwegian full-time college and university students in the age 18-35, has several interesting findings.”

It does not make sense to me whether you are talking about your study findings or the survey!

Response: We have now removed this sentence from the beginning of the Discussion.

2) “The observed prevalence of chronic pain in the current study was high but comparable to what has also been observed in similar studies. In a recent review and meta-analysis of chronic pain in epidemiological studies, a pooled chronic pain prevalence of 31% was reported, although the authors concluded that the lack of consistency in defining chronic pain makes evaluations and comparisons across study populations difficult”.

The prevalence of chronic pain in your study was around 54%! I do not think it is similar to the review that your reported which says 31%!

Response: We agree, and we have now changed this sentence to:

“The observed prevalence of chronic pain in the current study was even higher than what has been observed in similar studies.”

3) “Strengths of the SHoT study include the very large sample size, in combination with several well-validated questionnaires.”.

I think this sentence is related to the next paragraph!

Response: True. The paragraph outlining the study strengths have been modified accordingly.

4) Could you write a conclusion paragraph at the end of the DISCUSSION section?

Response: We have now added the following conclusion at the end of the discussion:

“The demonstrated health benefits of regular exercise suggest that facilitating young adults to become more physically active should be a prioritized task both for political and educational institutions.”

REVIEWER # 2

Although this paper is very well written and addresses an important topic, my biggest concern is whether psychological factors and economic factors have been considered as confounders among this group. This group is particularly at risk of depression due to financial issues (not sure if same in Norway as other countries) or family issues, and there is a known link between depression and chronic pain, and if not factored in could have influenced the results. In addition, Scandinavian countries are known for having a high prevalence of depression - due to factors such as weather, etc. Has this been factored in as confounders ? I see you have included economic status, but was this adjusted for as well? No psychological outcomes seem to have been measured.

Response: This is an important point, and we now include self-reported depression in the list of confounders. We have updated all relevant parts of the manuscript to reflect this change. Specifically related to the Tables, we have added a third column/Model to Table 2 and 3, labeled “Fully adjusted Model” in which we now additionally adjust for depression, plus the other confounders listed under “Adjusted Model”.

And then one other issue - in which language where all questionnaires/scales administered? Were those not previously validated and translated, translated and validated at any point among this group in this study? not clear from text, although reference made for certain tools.

Response: Where possible, questionnaires were administered using the validated Norwegian translation (e.g. physical exercise, sleep duration and AUDIT. Other questionnaires not previously translated into Norwegian were translated, and then back-translated to the original language (English), to ensure accuracy. This information has now been added to the Methods section. For the GRIP instrument, we also added the following text:

“Instructions and questions in GRIP were put in Norwegian. Translation to English was made by a certified translator, but back translation is still in process [16]”.

Submitted filename: PLOS One Response to Reviewers.docx

Click here for additional data file.

16 Jun 2020

Physical exercise and chronic pain in university students

PONE-D-20-09746R1

Dear Dr. Sivertsen,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Adewale L. Oyeyemi, Ph.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: No

Reviewer #2: No

18 Jun 2020

PONE-D-20-09746R1

Physical exercise and chronic pain in university students

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