1 Supplementary file 1. Eligibility criteria and CPM protocols across original studies

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Supplementary file 1. Eligibility criteria and CPM protocols across original studies

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CPM protocol – non-specific multisite pain (n=693)

Eligibility criteria

Patients with chronic pain referred to interdisciplinary pain treatment at a university hospital pain clinic in the period February 1, 2015 to April 1st, 2016 were included in this cross-sectional study. Inclusion criteria were men and women at least 18 years old, chronic nonmalignant pain for minimum 6 months, and patients should speak and understand Danish to ensure that they understood the information about the pain testing procedures. Exclusion criteria were pain primarily in the genital area and pregnancy.

CPM was assessed using a parallel design.

Test-stimulus (TS)

Pressure pain threshold assessed with computer-controlled cuff algometry on the non-dominant lower leg was used as the TS. A 13 cm silicone tourniquet (VBM, Sulz, Germany) was wrapped around the non- dominant lower leg, 5 cm below the tibial tuberosity. The pressure intensity was increased by 1 kPa/s with a maximum of 100 kPa. The pressure pain threshold was indicated by the participant on an electronic visual analog scale when the pressure was defined as the very first sensation of pain.

Conditioning stimulus (CS)

The conditioning stimulus was induced with tonic pressure of 30 kPa delivered by a 7.5 cm wide silicone tourniquet wrapped around the dominant lower leg, 8 cm from the tibial tuberosity.

During CS, the TS was reassessed as described above.

The duration of the CS was individual. The

conditioning stimulus lasted until the patient stopped the test stimulus and the CS when the test

stimulus was perceived as maximal /mean duration: 46±22 seconds.

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CPM protocol – patellofemoral pain (n=150)

To be included, volunteers had to be aged between 18 and 50 years with pain behind or around the patella aggravated by at least one weight-bearing activity on a flexed knee (walking, running, stair ambulation, squatting) and/or prolonged sitting. A pain duration of at least 6 weeks and a pain severity of ≥3/10 (0 =

“no pain” and 10 = “worst pain imaginable”) over the last week were required. Volunteers were excluded if they reported greater pain and/or more bothersome symptoms at other sites of body pain than the PFP; a history of patellar dislocation/subluxation associated with their knee pain; or neuromusculoskeletal conditions that impair sensory or physical function. As the study included cold pain threshold tests, individuals were excluded if they had conditions such as Raynaud's syndrome, peripheral neuropathy, and hypothyroidism, where testing procedures could compromise tissue integrity.

Conditioned pain modulation was assessed using a protocol previously performed in a patellofemoral pain cohort [1] with fair to good reliability [2]. For the conditioning stimulus, cold water immersion was applied to the hand. For the test stimulus, pressure pain threshold was measured at the centre of the patella (or the medial border of the patella) of the most painful knee.

Test stimulus – Pressure pain threshold

Pressure pain threshold (PPT) was measured using a handheld algometer (Somedic AB, Farsta, Sweden) with a probe size of 1cm². Handheld algometry has demonstrated excellent reliability in PFP [3]. Pressure was applied incrementally at a rate of 30 kPa/s until the participant indicated the first onset of pain. At first onset of pain, participants rated their pain intensity using an 11-point numerical pain rating scale (NPRS: 0 = no pain; 10 = the worst pain imaginable) [4]. Whenever PPTs were conducted, the mean of three tests were used in the analysis.

Conditioning stimulus – cold-water immersion

Cold water immersion was used as the conditioning stimulus to elicit pain between 4-6/10 (NPRS).

Participants were instructed to submerge their hand (opposite side to the most painful knee) into 15°C water.

After 45 seconds of immersion, participants rated their hand pain and the water temperature was adjusted until the target conditioning pain intensity was achieved. The time of exposure to the conditioning stimulus was on average 130.5 (SD 32.6) seconds. The temperature at which the target conditioning pain level was achieved was on average 13.2 (SD 1.9) degrees Celsius.

Procedure

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Prior to cold water immersion, PPT was assessed. Next participants submerged their hand in cold water and PPTs were repeated during the conditioning stimulus. Once the target conditioning pain intensity was reported, the hand was withdrawn from the water and PPTs immediately repeated. With pre-, during- and post-conditioning measures, conditioned pain modulation was calculated as the largest PPT change from that taken at pre-conditioning measure.

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CPM protocol – gluteal tendinopathy (n=39)

Volunteers were aged 18-70 years. Individuals with greater trochanteric pain syndrome (GTPS) were eligible if they experienced lateral hip pain rated [greater than or equal to] 2/10 on an 11-point numeric rating scale (NRS; 0 = no pain, 10 = worst pain imaginable) at its worst in the past week; pain duration of three or more months; pain on palpation of the tendon insertion on the greater trochanter, plus reproduction of trochanteric pain on at least one of the following clinical tests: 1) 30-second single-leg stance, 2) the Hip FADER test, 3) static muscle test in the FADER position, 4) the FABER test, 5) Ober's test, 6) a static muscle contraction in the Ober's test position. GTPS participants were excluded if they experienced groin pain on quadrant testing

>3/10 on the pain NRS, received a corticosteroid injection in the previous six months, experienced major trauma in the past 12 months, or had lower limb or back pain that was worse than their hip pain, required treatment, or prevented usual work or leisure activities in the previous six months. Pregnancy, systemic inflammatory or neurological disorders, uncontrolled diabetes, and fibromyalgia were general exclusion criteria.

Conditioned pain modulation was conducted by immersing the contralateral hand in a cold-water bucket (conditioning stimulus) and by measuring pressure pain threshold (PPT) as a testing stimulus over the lateral hip before, during and immediately after immersion of the hand.

Test stimulus – PPT

PPT was measured unilaterally at a local hip site (the most painful spot in GTPS; 1-2cm posterior to the greater trochanter in controls). PPT was measured using a pressure algometer (Somedic AB, Farsta, Sweden) with a probe size of 1cm², applied at a rate of 30 kPa/s until the first onset of pain was perceived or the cut- off threshold of 1000 kPa was reached.

The conditioning stimulus involved immersion of the contralateral hand in a cold-water bucket. The starting water temperature was ~10°C (range 9.5°C – 10.5°C). After a 30 second waiting period, the water

temperature was adjusted by adding warm or cold water until a pain intensity of 4-6/10 on a pain numeric rating scale was reported.

Procedure

Three PPT trails were conducted before, during and immediately after immersion of the hand. The highest PPT score recorded during or immediately post immersion of the hand was subtracted from the PPT score

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pre-immersion to calculate the CPM response. A positive CPM response (increase) reflects a hypo-algesic response, whereas a negative response (decrease) reflects a hyper-algesic response.

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CPM protocol – lateral elbow tendinopathy (n=132)

Volunteers were aged 18-70 years. Participants with lateral elbow tendinopathy were included if they had:

lateral elbow pain ≥6 weeks duration; average pain severity during the past week 2 on a 11-point numerical rating scale; provoked by at least 2 of gripping, palpation of the lateral epicondyle, stretching of the forearm muscles, or resisted wrist, second or thrid finger extension; and reduced pain-free grip strength. Participants were excluded if they had: other primary sources of elbow pain; concomitant musculoskeletal pain

conditions reported by participants to be their predominant complaint; any injections within the preceding 6 months, major neurological, inflammatory or systemic conditions; or major trauma, fracture or surgery in the last year.

Conditioned pain modulation (CPM) was assessed using immersion of the left foot in cold water as the conditioning stimulus (CS) and pressure pain threshold (PPT) over the lateral epicondyle on the affected arm as the test stimulus (TS).

PPT was measured using a pressure algometer (Somedic AB, Farsta, Sweden) with a probe size of 1cm², applied at a rate of 30 kPa/s until the first onset of pain was perceived or the cut-off threshold of 1000 kPa was reached.

The CS involved immersion of the left foot in a cold-water bucket set at an initial temperature of ~12°C.

After 30 seconds of immersion, the water temperature was adjusted by adding cold or warm water until a pain intensity of 40-60/100 on a 0-100 numerical rating scale was reached.

Procedure

3 trials of PPT were collected before, during and after cold-water immersion and the mean value was calculated for each time point. The maximum value of either the PPT measured during or after the CS was used in the analysis. The CPM response was calculated as the difference between the maximum PPT score obtained during or after the CS and PPT score obtained before the CS.

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CPM protocol – Low back pain (n=128) Eligibility criteria

LBP participants were recruited and assessed within 2 weeks of onset of an acute episode of LBP that was pre- ceded by at least 1 month without pain. A LBP episode was defined as pain that had lasted longer than 24 hours, caused functional limitation, and caused them to seek or seriously consider medical or allied health intervention. They were included if they continued to experience pain and disability in the week before assessment (see below). Participants were excluded from either group if they had known or suspected serious spinal pathology (eg, fracture, inflammatory/infective spinal disease, cauda equine syndrome, metastasis, and neurological disorders). Participants were also excluded if they were younger than 18 or older than 50 years old, had major pain or injury to other body regions in the previous 12 months, or had other major diseases or disorders (eg, chronic renal/ endocrine disorders).

Procedure

The conditioned pain modulation (CPM) paradigm was based on our previous work validating the use of pressure pain threshold (PPT) as a test stimulus (TS) and the lower back as an application site for either the test stimulus (TS) or conditioning stimulus (CS: noxious contact heat) [5]. Four body regions were selected for testing to explore variation in CPM magnitude at different body sites [6] and whether application of the TS/CS to the painful region in low back pain (LBP) participants affects the CPM response: (1) lower back (site of pain, (2) forearm (TS - proximal region of the muscle belly of extensor carpi radialis longus; CS - proximal volar aspect), and (3) thumbnail. Trials were conducted in three test blocks of different TS and CS arrangements in random order:

(1) TS – lower back, CS – contralateral forearm

(2) CS – lower back, TS – contralateral forearm and thumb

(3) CS – forearm (ipsilateral to lower back site), TS – contralateral forearm and thumb

In each block, the TS was first applied alone and then reapplied concomitantly with the CS 30 s after onset. The CS was maintained until all TS measurements had been completed (~60 s). A 15-min rest was enforced between blocks to eliminate any unresolved CPM effects [7].

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For the determination of PPT, a pressure algometer (Somedic A/B, Stockholm, Sweden) with a 1-cm disc-shaped probe head was applied at an increasing rate of ~40 kPa/s. Participants pressed a stop button when the stimulus changed from one of pressure to one of pain [8]. Three trials were performed at each site and a mean score in kPa was calculated.

Conditioning stimulus – suprathreshold heat pain

The CS involved contact heat pain produced by a computerized Peltier based contact stimulation device (PATHWAY Pain and Sensory Evaluation System, Medoc Ltd., Israel) with a 30 x 30 mm probe.

Unlike limb immersion techniques (e.g. hand immersion in painfully hot or cold water), this form of stimulation enabled application of a CS to the back. CS intensity was determined at the start of the session for each test site using a heat pain threshold (HPT) paradigm. Beginning at a temperature of 32 °C, eight ascending heat stimuli were applied with a rate of temperature change of 0.7 °C/s, and an inter-stimulus interval of 10 s. Participants signalled the onset of pain by pressing a button, and the temperature

immediately returned to baseline. HPT was identified as the mean of the final five trials. The CS was set at 1°C above the HPT. Some participants were unable to tolerate this CS during CPM trials, and the CS was reduced at 0.5 °C increments until reported pain scores were below “80” out of 100 on a numerical rating scale (NRS) anchored with “no pain” at 0 and “worst pain imaginable” at 100. If the CS intensity was less than “45” on the NRS, the temperature was increased until pain was reported above “45” on the NRS. This

“revised” temperature was then used for all remaining CPM trials that involved the same CS test site unless further modifications were required (i.e. increase or decrease temperature). This procedure ensured the CS was safe and sufficiently intense to induce CPM over a short application time.

During CPM testing, the CS was applied at an initial temperature of 32 °C before rising at a rate of 0.7 °C/s to the predetermined intensity. Temperature was returned to baseline at 7°C/s immediately

following the completion of both TS measurements. During exposure to the CS, participants reported the

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pain intensity caused by the CS on the NRS three times: at 0 s, 30 s, and just prior to cessation of the CS (i.e.

after the last TS recording).

Quantifying CPM

The CPM response was calculated as the difference between the TS scores obtained before and during the CS [9]. A higher TS score during the CS than baseline indicated pain inhibition (expressed as a positive value). A lower TS scores during the CS than baseline indicated pain facilitation (negative value) [10, 11].

References

1. Rathleff, M.S., et al., Adults with patellofemoral pain do not exhibit manifestations of peripheral and central sensitization when compared to healthy pain-free age and sex matched controls – An

assessor blinded cross-sectional study. PloS one, 2017. 12(12): p. e0188930-e0188930.

2. Kennedy, D.L., et al., Reliability of conditioned pain modulation: A systematic review. Pain (Amsterdam), 2016. 157(11): p. 2410-2419.

3. van der Heijden, R.A., et al., Strength and Pain Threshold Handheld Dynamometry Test Reliability in Patellofemoral Pain. International journal of sports medicine, 2015. 36(14): p. 1201-1205.

4. Kelly, K.G., T. Cook, and M.-M. Backonja, Pain ratings at the thresholds are necessary for interpretation of quantitative sensory testing. Muscle & nerve, 2005. 32(2): p. 179-184.

5. Klyne, D.M., et al., Effect of types and anatomic arrangement of painful stimuli on conditioned pain modulation. J Pain, 2015. 16(2): p. 176-85.

6. Pud, D., Y. Granovsky, and D. Yarnitsky, The methodology of experimentally induced diffuse noxious inhibitory control (DNIC)-like effect in humans. Pain, 2009. 144(1-2): p. 16-9.

7. Willer, J.C., A. Roby, and D. Le Bars, Psychophysical and electrophysiological approaches to the pain-relieving effects of heterotopic nociceptive stimuli. Brain, 1984. 107 ( Pt 4): p. 1095-112.

8. Sterling, M., Testing for sensory hypersensitivity or central hyperexcitability associated with cervical spine pain. J Manipulative Physiol Ther, 2008. 31(7): p. 534-9.

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9. Yarnitsky, D., et al., Recommendations on terminology and practice of psychophysical DNIC testing.

Eur J Pain, 2010. 14(4): p. 339.

10. Yarnitsky, D., et al., Prediction of chronic post-operative pain: pre-operative DNIC testing identifies patients at risk. Pain, 2008. 138(1): p. 22-8.

11. Yarnitsky, D., et al., Recommendations on practice of conditioned pain modulation (CPM) testing.

Eur J Pain, 2015. 19(6): p. 805-6.

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Supplementary file 2. Mean ± SD CPM effect for the total sample and within each patient cohort.

In addition, the number of participants (percentage) dichotomized as CPM-responder defined as an increase in test stimulus larger than 0% for the total sample and within each patient cohort.

CPM effect (%)

Mean ± SD

CPM-responders

NSMP 18.0 ± 39.7 454 (66%)

PFP 25.9 ± 30.4 129 (86%)

LBP 11.2 ± 18.9 84 (66%)

LET 16.6 ± 23.9 99 (75%)

GT 31.5 ± 63.3 22 (60%)

TOTAL 18.5 ± 26.5 788 (69%)

NSMP, non-specific musculoskeletal pain; PFP, patellofemoral pain; LBP, low back pain; LEP,

lateral elbow tendinopathy; GT, gluteal tendinopathy.

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Supplementary file 3. Number of participants dichotomized as psychological cases for each

psychological construct. Data is presented in numbers (percentage) for the total sample and within each patient cohort.

Participants identified as cases per psychological construct

Anxiety Depression Catastrophiz ing

Fear of movement

NSMP 103 (21%) 108 (23%) 364 (55%) 374 (58%)

PFP 28 (19%) 13 (9%) 11 (7%) 59 (39%)

LBP - 43 (33%) 24 (19%) -

LET 30 (23%) 12 (9%) 6 (5%) 26 (20%)

GT 2 (5%) 2 (5%) 1 (3%) 8 (21%)

TOTAL 163 (20%) 178 (19%) 406 (36%) 467 (48%)

NSMP, non-specific musculoskeletal pain; PFP, patellofemoral pain; LBP, low back pain; LEP,

lateral elbow tendinopathy; GT, gluteal tendinopathy.

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Supplementary file 4. Generalized linear models assessing the association between conditioned pain modulation and the psychological factors per protocol.

Table 1A – Protocol NSMP (n=693). Generalized linear models assessing the association between the conditioned pain modulation effect score (z-scores) as dependent variable and anxiety, depression,

catastrophizing and fear of movement as independent variables, adjusted for age, sex, body mass index and pain duration.

Variables N Beta SE P-value 95%CI

Anxiety (non-case) 452 -0.00 0.12 0.98 0.23, 0.00

Sex 0.41 0.10 <0.001* 0.61, 0.03

Age -0.01 0.00 0.02* -0.00, 0.01

BMI -0.02 0.01 0.03* -0.00, 0.01

Pain duration - - - -

Depression (non-case) 450 -0.05 0.11 0.67 0.17, 0.00

Sex 0.44 0.10 <0.001* 0.64, 0.04

Age -0.01 0.00 0.03* -0.00, 0.01

BMI -0.02 0.01 0.05 -0.00, 0.01

Catastrophizing (non-case) 621 0.08 0.08 0.33 -0.08, 0.23

Sex 0.42 0.08 <0.001* 0.26, 0.59

Age -0.01 0.00 0.01* -0.02, -0.00

BMI -0.02 0.01 0.03* -0.03, -0.00

Fear of movement (non-case) 606 0.11 0.08 0.16 -0.04, 0.27

Sex 0.41 0.09 <0.001* 0.24, 0.57

Age -0.01 0.00 0.01* -0.01, -0.00

BMI -0.01 0.01 0.06 -0.03, 0.00

Abbreviations: BMI, body mass index; N, number of participants; SE, standard error; 95%CI, 95%

confidence interval. *Indicates a significant P-value.

Table 1B - Protocol NSMP (n=693). Generalized linear model with the cumulative psychological score (0- 3, sum of cases for depression, catastrophizing, fear of movement) as the independent variable and

continuous conditioned pain modulation effect (Z-score) as the dependent variable.

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Variables Beta SE P-value 95%CI

0 psych cases (n=113) -0.01 0.16 0.97 -0.31, 0.30

1 psych cases (n=127) -0.25 0.15 0.10 -0.55, 0.05

2 psych cases (n=137) -0.21 0.15 0.17 -0.50, 0.09

3 psych cases (n=65) - - - -

Sex 0.43 0.10 <0.001* 0.23, 0.64

Age -0.01 0.00 0.04* -0.02, 0.00

BMI -0.02 0.01 0.04* -0.03, 0.00

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Table 2A – Protocol PFP (n=150) . Generalized linear models assessing the association between the conditioned pain modulation effect score (z-scores) as dependent variable and anxiety, depression,

Anxiety (non-case) 150 0.43 0.21 0.04* 0.01, 0.84

Sex 0.28 0.17 0.11 -0.06, 0.62

Age -0.02 0.01 0.03* -0.04, -0.00

BMI 0.30 0.02 0.12 -0.01, 0.07

Pain duration -0.17 0.31 0.58 -0.79, 0.44

Depression (non-case) 150 -0.11 0.29 0.71 -0.68, 0.46

Sex 0.29 0.17 0.09 -0.05, 0.64

Age -0.02 0.01 0.06 -0.04, 0.00

BMI 0.03 0.02 0.12 -0.01, 0.07

Pain duration -0.24 0.31 0.44 -0.86, 0.37

Sex 0.27 0.17 0.12 -0.07, 0.62

Age -0.02 0.01 0.06 -0.04, 0.00

BMI 0.03 0.02 0.11 -0.01, 0.07

Pain duration -0.22 0.31 0.48 -0.84, 0.40

Sex 0.33 0.18 0.07 -0.03, 0.68

Age -0.02 0.01 0.05 -0.04, 0.00

BMI 0.03 0.02 0.12 -0.01, 0.07

Pain duration -0.24 0.31 0.45 -0.86, 0.38

Table 2B - Protocol PFP (n=150) . Generalized linear model with the cumulative psychological score (0-3, sum of cases for depression, catastrophizing, fear of movement) as the independent variable and continuous conditioned pain modulation effect (Z-score) as the dependent variable.

0 psych cases (n=86) 0.74 0.72 0.30 -0.67, 2.16

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1 psych cases (n=47) 0.78 0.72 0.28 -0.65, 2.21

2 psych cases (n=15) 0.61 0.75 0.42 -0.88, 0.20

3 psych cases (n=2) - - - -

Sex 0.30 0.18 0.10 -0.06, 0.65

Age -0.02 0.01 0.06 -0.04, 0.00

BMI 0.03 0.02 0.09 -0.01, 0.07

Pain duration -0.23 0.31 0.46 -0.85, 0.39

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Table 3A – Protocol LBP (n=128) . Generalized linear models assessing the association between the conditioned pain modulation effect score (z-scores) as dependent variable and anxiety, depression,

Sex 0.07 0.20 0.72 -0.32, 0.46

Age 0.01 0.01 0.49 -0.01, 0.03

BMI -0.03 0.02 0.30 -0.07, 0.02

Catastrophizing (non-case) 127 -0.04 0.23 0.86 -0.51, 0.42

Sex 0.04 0.19 0.84 -0.33, 0.40

Age 0.01 0.01 0.50 -0.02, 0.03

BMI -0.02 0.02 0.32 -0.07, 0.02

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Table 3B - Protocol LBP (n=128) . Generalized linear model with the cumulative psychological score (0-3, sum of cases for depression, catastrophizing, fear of movement) as the independent variable and continuous conditioned pain modulation effect (Z-score) as the dependent variable.

0 psych cases (n=74) 0.12 0.30 0.69 -0.47, 0.71

1 psych cases (n=39) 0.52 0.31 0.10 -0.10, 1.15

2 psych cases (n=14) - - - -

Sex 0.14 0.19 0.48 -0.24, 0.52

Age 0.01 0.01 0.59 -0.02, 0.03

BMI -0.02 0.02 0.35 -0.07, 0.02

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Table 4A – Protocol LET (n=132) . Generalized linear models assessing the association between the conditioned pain modulation effect score (z-scores) as dependent variable and anxiety, depression,

Anxiety (non-case) 132 -0.37 0.22 0.09 -0.80, 0.06

Sex 0.09 0.19 0.62 -0.28, 0.46

Age 0.00 0.01 0.95 -0.02, 0.02

BMI -0.00 0.02 0.90 -0.04, 0.03

Pain duration -0.22 0.23 0.32 -0.67, 0.22

Sex 0.11 0.19 0.57 -0.26, 0.48

Age -0.00 0.01 0.88 -0.02, 0.02

BMI -0.00 0.02 0.86 -0.04, 0.03

Pain duration -0.26 0.23 0.27 -0.72, 0.20

Catastrophizing (non-case) 132 -0.13 0.43 0.76 -0.99, 0.73

Sex 0.11 0.19 0.58 -0.27, 0.48

Age -0.00 0.01 0.82 -0.02, 0.02

BMI -0.01 0.02 0.74 -0.04, 0.03

Pain duration -0.17 0.23 0.46 -0.62, 0.28

Sex 0.11 0.19 0.56 -0.26, 0.48

Age -0.00 0.01 0.76 -0.02, 0.02

BMI -0.01 0.02 0.72 -0.04, 0.03

Pain duration -0.21 0.23 0.37 -0.66, 0.25

Table 4B - Protocol LET (n=132) . Generalized linear model with the cumulative psychological score (0-3, sum of cases for depression, catastrophizing, fear of movement) as the independent variable and continuous conditioned pain modulation effect (Z-score) as the dependent variable.

0 psych cases (n=99) -0.41 0.73 0.58 -1.86, 1.04

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1 psych cases (n=23) -0.71 0.76 0.36 -2.21, 0.80

2 psych cases (n=7) -0.21 0.83 0.80 -1.85, 1.43

Sex 0.10 0.19 0.61 -0.28, 0.47

Age -0.00 0.01 0.88 -0.02, 0.02

BMI -0.01 0.02 0.61 -0.05, 0.03

Pain duration -0.20 0.23 0.40 -0.66, 0.27

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Table 5A – Protocol GT (n=39) . Generalized linear models assessing the association between the conditioned pain modulation effect score (z-scores) as dependent variable and anxiety, depression,

Anxiety (non-case) 37 -1.29 0.75 0.09 -2.81, 0.23

Sex 0.85 0.75 0.27 -0.68, 2.37

Age 0.02 0.02 0.23 -0.02, 0.06

BMI 0.01 0.03 0.68 -0.04, 0.07

Sex 0.85 0.75 0.27 -0.68, 2.37

Age 0.02 0.02 0.23 -0.02, 0.06

BMI 0.01 0.03 0.68 -0.04, 0.07

Sex 0.74 0.78 0.35 -0.85, 2.32

Age 0.02 0.02 0.37 -0.02, 0.06

BMI 0.01 0.03 0.68 -0.05, 0.08

Sex 0.62 0.78 0.43 -0.96, 2.20

Age 0.02 0.02 0.34 -0.02, 0.06

BMI 0.00 0.03 1.00 -0.06, 0.06

Table 5B - Protocol GT (n=39) . Generalized linear model with the cumulative psychological score (0-3, sum of cases for depression, catastrophizing, fear of movement) as the independent variable and continuous conditioned pain modulation effect (Z-score) as the dependent variable.

0 psych cases (n=27) -1.97 0.99 0.06 -4.00, 0.06

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1 psych cases (n=9) -2.50 1.03 0.02* -4.60, -0.41

Sex 0.70 0.72 0.34 -0.78, 2.17

Age 0.02 0.02 0.26 -0.02, 0.06

BMI 0.02 0.03 0.54 -0.04, 0.07