The effects of pain science education plus exercise on pain and function in chronic Achilles tendinopathy: a blinded, placebo-controlled, explanatory, randomized trial : PAIN

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Research Paper

The effects of pain science education plus exercise on pain and function in chronic Achilles tendinopathy: a blinded, placebo-controlled, explanatory, randomized trial

Chimenti, Ruth L.a,*; Post, Andrew A.a; Rio, Ebonie K.b; Moseley, G. Lorimerc; Dao, Megana; Mosby, Hadleya; Hall, Medericd,e; de Cesar Netto, Cesare; Wilken, Jason M.a; Danielson, Jessicaf; Bayman, Emine O.g; Sluka, Kathleen A.a

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PAIN 164(1):p e47-e65, January 2023. | DOI: 10.1097/j.pain.0000000000002720
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  • Global Year 2023

1. Introduction

Chronic pain affects 20% to 30% of adults and adversely impacts both physical and mental health.8,35 Exercise is a low risk, multimodal treatment that reduces pain for a wide variety of chronic musculoskeletal conditions.10,20 For chronic Achilles tendinopathy (AT), randomized controlled trials (RCTs) report clinically meaningful reductions in pain using a variety of exercise programs,3,59,61 which are now considered a first-line intervention for AT. However, 20% to 50% of individuals with AT continue to have pain following rehabilitation.41,53,57 The majority of individuals with AT report elevated fear of movement,11,12,23 which is associated with more severe pain and may interfere with exercise participation and recovery.12 Given that patient education focusing on pain mechanisms has been shown to reduce fear of movement and pain catastrophizing in other musculoskeletal conditions,56 the addition of education could potentially enhance the effectiveness of exercise in improving symptoms in individuals with AT.

Combining pain science education (PSE) with exercise can impart a greater reduction in pain and disability than exercise alone, as demonstrated in a recent meta-analysis of 5 RCTs for chronic musculoskeletal pain.56 While these findings support the use of PSE as an adjunct to exercise, it is unclear if this effect will be maintained when a placebo education with an equivalent exercise program is used in comparison. Moreover, the effectiveness of PSE plus exercise on other pain-related factors, such as performance-based function, psychosocial factors, and central nervous system (CNS) nociceptive processing, is still unclear.19,22,30,32,42,45,48

There is a quickly emerging field of research on movement-evoked pain,5,13,18 which is distinct from resting pain and assesses pain within a clinically relevant context. For individuals with AT, movement-evoked pain with tendon-loading exercise is routinely used to individualize assessment of AT severity and determine exercise progression.59 Given that AT pain primarily occurs with movement, this may contribute to and reinforce elevated fear of movement, which is common among this patient population.12 The key components of PSE are providing a greater understanding of the multidimensionality of pain and helping patients reconceptualize the pain experience. Therefore, we designed a placebo education that focused on the pathoanatomical pathology of the tendon. The primary objective of this blinded, placebo-controlled, randomized, explanatory trial is to determine if PSE plus exercise is more effective at reducing pain and improving function than a placebo, pathoanatomical education (PAE) plus exercise in patients with chronic AT. The second objective of this RCT is to determine the magnitude of change in pain-related factors (performance-based function, psychosocial factors, CNS nociceptive processing) with an exercise program, regardless of education type. Additional exploratory aims to investigate those factors (demographics, change in knowledge, performance-based function, psychosocial factors, CNS nociceptive processing, therapeutic alliance, anticipated global rating of change) that are associated with greater short-term improvements in pain and self-reported function.

2. Methods

2.1. Trial design and randomization procedures

This blinded, placebo-controlled, randomized explanatory trial used a 2-group parallel design. The study recruiter enrolled participants into the study before they were assigned a treatment group. The outcome assessor confirmed informed consent and completed postconsent screening during the first evaluation visit. Participants were randomized to study groups using permuted block design with variable block sizes. Randomization was stratified such that each intervention arm was balanced based on (1) sex and (2) type of AT (insertional or midportion). Up to 24 hours prior to the first treatment visit, the physical therapist received the intervention arm assignment from a research staff member, whose role was separate from the recruiter and outcome assessor. Participants were randomized to 1 of 2 arms: PSE or PAE. The 2 education programs were equivalent in terms of the quality of the materials (videos and handouts), time (with the clinician during sessions and homework completed by the participant between sessions), provider, and level of evidence-based content. The primary difference between the education programs was the emphasis on the potential mechanism(s) of pain (biopsychosocial vs biomedical) in the content provided to participants. The education was provided in combination with the same progressive tendon-loading exercise intervention (intervention described more in depth below). Each participant completed an initial evaluation with the outcome assessor at 0 weeks, had 6 to 7 individual weekly treatment sessions with a physical therapist between weeks 1 to 7, followed by an evaluation session with the outcome assessor at 8 weeks. Surveys were also completed at 12 weeks. The treating licensed physical therapist had 7 years of clinical experience with additional training as an Orthopaedic Clinical Specialist and as a Fellow of the American Academy of Orthopaedic Manual Physical Therapy.

2.2. Alterations to study after initiation

In March 2020, after the study was initiated, alterations were made to the study design due to the COVID-19 pandemic, aiming to maintain the health and safety of participants and the study team, which were detailed in a protocol article published in November 202047 and subsequently updated in real time on the open science framework registration (osf.io/jf2xu). In accordance with COVID-19 policies at the University of Iowa Hospitals and Clinics, in-person human subject research was suspended from March 17, 2020 to July 15, 2020. Additionally, in-person human subject research was completed in an alternate laboratory space without a 3-dimensional (3D) motion capture system from November 18, 2020 to December 14, 2020, due to suspension of in-person human subject research within hospital-based laboratories. After July 15, 2020, all evaluation visits were completed in-person, except for one participant due to caution about potential COVID-19 symptoms. Treatment visits were completed using a hybrid of in-person and virtual visits according to the participant's preference. The content of the intervention, review of online educational homework, and progression of tendon-loading exercises as instructed by a physical therapist during the one-on-one sessions, all remained unchanged throughout the duration of the study.

2.3. Ethics approval and trial registration

All study procedures were approved by the University of Iowa Institutional Review Board and reviewed by the study sponsor. All participants signed informed consent documents prior to study participation. Before enrollment of the first participant, the study was registered at clinialtrials.gov (NCT 04059146) and Open Science Framework (osf.io/jf2xu).

2.4. Participants

Participants were identified and recruited through university mass emails, databases of participants previously enrolled in research studies, referrals from participants and collaborators in the Department of Orthopaedics and Rehabilitation, and review of electronic medical records for patients treated for Achilles tendon pain within the University of Iowa Hospitals and Clinics system over the previous 3 years. People who were interested in participating completed an online screening form, which was reviewed over the phone and/or by video with a study coordinator prior to scheduling the first evaluation. A total of 313 potential participants completed an online screening from September 2019 and December 2020 (Fig. 1). During the preconsent screening phase, 145 people did not meet the eligibility criteria, 45 people initially expressed interest in participating but then stopped responding to emails or phone calls, and 30 people were eligible but declined to participate. After informed consent, a physical therapist with more than 10 years of experience performed a standardized clinical examination, including obtaining patients' history, reviewing completed surveys, and assessing movement-evoked pain during Achilles tendon-loading exercises. Among the 93 consented participants, 27 participants did not meet the eligibility criteria. The other 66 participants were randomized into either the PSE or PAE arm of the study.

F1
Figure 1.:
Consolidated Standards of Reporting Trials (CONSORT) flow chart of the study participants with Achilles tendinopathy (AT) through the clinical trial comparing Pain Science Education (PSE) plus exercise to Pathoanatomical Education (PAE) plus exercise.

Adults with chronic AT participated in the study. Inclusion criteria were (1) primary location of pain at the Achilles tendon insertion or midportion sites evoked with weight-bearing activities; (2) localized pain of ≥ 3/10 in the Achilles tendon (midportion or insertional, unilateral, or bilateral) during walking, heel raises, or hopping at evaluation session 1; and (3) pain that increased (≥1 point on 11-point Numeric Rating Scale) with heel raises or hopping during the first evaluation session. Exclusion criteria were (1) younger than 18 years; (2) inability to read or write in English; (3) Achilles tendon pain for <3 months; (4) history of Achilles tendon rupture that was verified by surgical or conservative management; (5) history of invasive intervention (open, endoscopic, or ultrasound-guided procedure) for AT on more painful side; (6) noninvasive treatment (physical therapy, nitroglycerine patch, iontophoresis, and injection) for AT in the past 3 months; (7) systemic inflammatory conditions (eg, rheumatoid arthritis and ankylosing spondylitis), endocrine disorder with complications (eg, uncontrolled type 1 or 2 diabetes and diabetic peripheral neuropathy), or connective tissue disorder (eg, Marfan syndrome); (8) cardiovascular conditions that may be exacerbated by a 90-second submersion of hand in cold water (Raynaud and cold contact urticaria); (9) use of fluoroquinolones in the past 3 months; (10) clinical examination at the evaluation visit indicating foot and ankle pain primarily owing to other causes; (11) high risk for falls (4 Step Square Test > 15 seconds14 OR Stopping Elderly, Death, and Injuries [STEADI] score > 451); and (12) cardiovascular condition that prevents participation in an exercise program. Two additional exclusion criteria for virtual visits were (13) symptoms indicating the need for in-person blood pressure monitoring: (1) inconsistent use of hypertension medications and/or (2) any recent/current associated symptoms with uncontrolled hypertension; and (14) inability to successfully complete virtual visits with a webcam and/or prefer in-person visits.

2.5. Sample size determination

A power analysis was performed a priori and indicated that 66 participants were needed to account for a 10% attrition rate.47 At least 30 participants per group allowed us to detect improvement from 0 to 8 weeks with 80% power at an alpha level of 0.05 (Bonferroni corrected for 2 comparisons: movement-evoked pain and self-reported function). The anticipated change was estimated based on a previous RCT with movement-evoked pain (mean between group improvement = 0.75, SD = 1.05, effect size of f = 0.36) and self-reported function (between-group difference = 1.95, SD = 2.33, effect size of f = 0.42).38 This sample size also provided sufficient power to detect within-group improvement in performance-based function, psychosocial factors, and signs of altered CNS processing with a Cohen d > 0.43 (Bonferroni corrected for 3 comparisons). Further details on the power analysis are in the protocol article.47

2.6. Interventions

2.6.1. Design and format

The initial treatment visit was 45 minutes, and subsequent treatment visits were 30 minutes. The intervention provided equitable treatment time for both groups and was delivered by the same physical therapist. Immediately following the evaluation session and prior to randomization, the outcome assessor provided all participants with a handout and link to a video that introduced the rationale and progression of the tendon-loading exercises as homework to complete prior to their first session with the treating physical therapist. All participants were also instructed in isometric exercises to begin prior to their first treatment visit. Participants who had pain that was aggravated by ankle dorsiflexion, mostly those with insertional AT, were given heel lifts to use in their shoes during isometric exercises and daily activities that aggravated AT symptoms. From 1 week to 7 weeks, participants had 6 to 7 one-on-one visits with a physical therapist in-person at a laboratory setting or virtually via video conferencing. From 9 to 12 weeks, participants were instructed to maintain their home exercise program. At 10 weeks, the physical therapist reached out via phone and/or email to address any questions regarding exercise progression.

To provide equitable delivery of education programs, the videos, handouts, and review questions were similar in length, style, and presentation of content, including the use of a script by the physical therapist to maximize consistency. The education program included homework that consisted of watching a 5- to 10-minute video, reviewing a handout that summarized video content, answering 3 to 5 multiple-choice questions on video content, and completing 1 to 2 short-answer questions about personal experiences that related to video content. The physical therapist spent 10 to 15 minutes at the start of each treatment visit discussing the participants' responses to the homework questions. All educational materials, including links to videos, PDFs of handouts, and review questions, were provided electronically through an electronic data management system (REDCap).

The education component was provided primarily during the first half of the treatment visit and was integrated with the exercise program during the second half of the treatment visit. Overall, the education programs provided information on the causes of pain, a rationale for the treatment, and the importance of exercise. Educational content differed between groups with those in the PSE group focused on biopsychosocial mechanisms of pain and those in the PAE education group focused on biomedical aspects of pain. Both groups also had similar homework for the last treatment visit (ie, visit #6), which introduced the importance of maintaining a home exercise program from weeks 9 through 12 and beyond and of achieving the general physical activity guidelines by the Department of Health and Human Services.44

2.6.2. Pain science education

The goals of the PSE were to (1) learn about the neurophysiology of pain from a biopsychosocial perspective, (2) apply knowledge about fear of movement and pain catastrophizing during participation in a progressive tendon loading program, and (3) promote increased physical activity as a means of decreasing pain and maintaining pain relief. The education included selected content developed by the Explain Pain, Retrain Pain Foundation, and Cognitive Therapy for Chronic Pain.36,37,55,64,65 The videos for the pain science education program and educational handouts can be accessed through Iowa Research Online, available at https://doi.org/10.25820/data.006166.

2.6.3. Pathoanatomical education

The goals of the PAE were to (1) learn about pathophysiology of Achilles tendinopathy, including potential biomedical sources of pain, (2) apply knowledge about pathoanatomy during participation in a progressive tendon loading program, and (3) promote participation in exercise as a means of improving overall physical health. The education included selected content by the American Physical Therapy Association, the American Academy of Orthopaedics, and the FIFA Medical Network.1,16,31

2.6.4. Exercise program

All participants completed the same exercise program with instructions given during a one-on-one session with a physical therapist and reinforced with a video and handouts. The exercise program progressed through 3 phases: isometric, heel raise, and spring. Progression from 1 phase to the next was based on time frame and predetermined criteria based on symptoms and ability to complete exercises (Fig. 2). If a participant had a flare up in symptoms, then exercises from the current phase were reduced and/or exercises from the previous phase were used. For example, if a participant's AT symptoms increased during the heel raise phase, then the participant was instructed to reduce height of heel raise motion, decrease the number of repetitions, and/or to replace the heel raises with isometrics until symptom aggravation resolved. To keep the exercise program consistent for both midportion and insertional AT, all participants were instructed to complete the concentric and eccentric heel raises on level ground and not to perform over the edge of step.28 Participants were encouraged to maintain and/or gradually increase their recreational exercise throughout study participation. Participants were given modifications (eg, wear heel lifts in shoes, use a shorter stride, alter duration of activity participation) to minimize aggravating AT symptoms during therapeutic exercise and recreational exercise. From 8 to 12 weeks, participants were instructed to maintain their exercise program to continue increasing their duration and level of recreational exercise.

F2
Figure 2.:
The exercise progression included 3 phases: isometric, heel raise, and spring. The week that participants started the second 2 phases depended on individualized criteria. Each phase built on the previous phase yet was unique due to the addition of new exercises at a specified dose and frequency.

2.7. Assessment of outcomes

Outcomes were evaluated at 3 timepoints: 0 weeks, 8 weeks (primary end point), and 12 weeks. Outcomes were collected at the evaluation visits (0 and 8 weeks) by a physical therapist who was blinded to the treatment group of each participant. In-person evaluation visits were 1.5 to 2 hours and included 3D motion analysis as well as sensory testing within a laboratory setting. Evaluation visits via video conferencing were 0.5 to 1 hour and included two-dimensional (2D) motion analysis to evaluate motor function, but no 3D motion analysis or sensory testing. Outcome data at 12 weeks were collected via an automated email that provided a link to complete an online survey. Participants received a $25 gift card for completing the evaluation visit at 0 weeks, a $50 gift card for completing the evaluation at 8 weeks, and $25 for completing the survey at 12 weeks. Reimbursement for parking and travel was also provided.

2.8. Measures

Five outcome domains were assessed over time (Table 1). Each domain had primary and secondary outcomes identified a priori, as described in the protocol article.47 All primary outcomes are described in detail below as well as secondary outcomes related to the primary aims of this study. Due to COVID-19 restrictions on in-person human subject research, some measures were adapted to a virtual format (ie, movement-evoked pain and 2D motion analysis), but sensory testing and 3D motion analysis were not completed virtually.

Table 1 - Methods used to assess primary (*) and secondary outcomes within each domain at each timepoint.
Domain Variable 0 wk 8 wk 12 wk
AT symptoms *Movement-evoked pain during heel raises In-person/zoom In-person/zoom
Movement-evoked pain during hops In-person/zoom In-person/zoom
Expected pain during heel raises Survey Survey Survey
Expected pain during hops Survey Survey Survey
Average duration of tendon stiffness Survey Survey Survey
Self-reported function *PROMIS Physical Function Survey Survey Survey
VISA-A Survey Survey Survey
Performance-based function *Number of single limb heel raises In-person/zoom In-person/zoom
Heel raise work In-person/zoom In-person/zoom
Hop height In-person In-person
Peak ankle power during walking at self-selected speed, walking at a standardized speed, and during hopping In-person In-person
Psychosocial factors *Tampa Scale of Kinesiophobia Survey Survey Survey
Pain Catastrophizing Scale Survey Survey Survey
PROMIS Self-efficacy for Managing Symptoms Survey Survey Survey
PROMIS Anxiety Survey Survey Survey
PROMIS Depression Survey Survey Survey
CNS nociceptive processing *CPM at Achilles tendon In-person In-person
CPM at semitendinosus tendon In-person In-person
Temporal summation In-person In-person
PPT at Achilles tendon on involved side In-person In-person
PPT at Achilles tendon on contralateral side In-person In-person
CHOIR body map Survey Survey Survey
Symptom Severity Score Survey Survey Survey
AT, Achilles tendinopathy; CHOIR, Collaborative Health Outcomes Information Registry body map; CNS, central nervous system; CPM, conditioned pain modulation; PPT, pressure pain threshold; PROMIS, Patient-Reported Outcomes Measurement Information System; VISA-A, Victorian Institute of Sport Assessment-Achilles. * indicates primary outcome.

2.8.1. Descriptive variables and knowledge assessment

We obtained demographic variables for all study participants who were randomized to a treatment group. Participants were asked from which providers they received care for AT. Participants were also asked what treatments they had tried for AT and which treatments they found effective for reducing AT symptoms. The knowledge assessment was completed prior to (0 weeks) and immediately following (8 weeks) the education program. The knowledge assessment included 9 multiple-choice questions with a higher score indicating more correct answers: 4 questions were specific to pain science education content (range 0-4), 4 questions were specific to the pathoanatomical content (range 0-4), and 1 question was specific to physical activity guidelines (range 0-1).

2.8.2. Pain

The primary pain outcome was movement-evoked pain during heel raises. Movement-evoked pain was selected as a primary outcome measure for pain to be consistent with previous clinical trials for AT.3,50,59 Movement-evoked pain was specific to the task of heel raises rather than hopping because we anticipated that many participants would be unable to complete a single leg hop. The verbal numeric pain rating scale (0-10) was used to rate movement-evoked pain during heel raises and hops at evaluation visits. Immediately following the movement, participants were asked to rate the worst pain in the Achilles tendon during the tendon-loading exercise. The minimal clinically important difference (MCID) for pain on an 11-point scale is 2 points.42,52 Expected pain (visual analog scale, 0-100) during heel raises and hops was assessed after asking the participants to view images or videos of the task.12 For average stiffness duration, participants were asked, “For how many minutes do you have stiffness in the Achilles tendon region on first getting up” (0 to >100 minutes). For anticipated global rating of change, an online survey at 0 weeks asked participants to, “Please rate the anticipated overall condition of your Achilles tendon by the time that you complete physical therapy 12 weeks from now.” Response options were on a 15-point scale ranging from +7, “A very great deal better,” to 0, “About the same,” to −7, “A very great deal worse.” Similarly, participants were asked to rate their global rating of change at 8 and 12 weeks: “Please rate the overall condition of your Achilles tendon from the time that you began physical therapy until now.”

2.8.3. Self-reported function

The primary outcome for self-reported function was the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function v2.0 computer adaptive testing (CAT).9 The PROMIS Physical Function was chosen as the primary outcome based on its previous use in the AT population,2 availability of normative values established for the general population,9 and ability to compare level of function to other patient populations. For PROMIS Physical Function, the general population has a mean t-score of 50 with a SD of 10 points, with a score lower than 40 considered impaired. The MCID for the PROMIS Physical Function CAT for lower extremity orthopedic conditions is 7.6 to 8.4.27 We also used the Victorian Institute of Sport Assessment-Achilles questionnaire (VISA-A) to assess function and activity.49 The total score can range from 0 (high disability and severe AT symptoms) to 100 points (high function and no AT symptoms). The MCID for the VISA-A is 10 points.39

2.8.4. Psychosocial factors

The primary outcome was fear of movement, which was assessed with the Tampa Scale of Kinesiophobia (TSK).63 The TSK was chosen as a primary outcome due to our previous work indicating that this particular pain-related psychosocial factor is commonly elevated among individuals with AT.11 The TSK has 17 items that participants rated on a scale from 1 to 4 based on their level of fear about movement causing pain and injury. A score of ≥37 indicates elevated kinesiophobia.69 The minimal important change is 5.5, as reported in a study of patients with acute low back pain who completed a rehabilitation program.34 The Pain Catastrophizing Scale (PCS) rates how often a participant has catastrophizing thoughts toward pain, with a score of ≥30 indicative of elevated pain catastrophizing.62 Patient-reported outcomes measurement information system CAT was used to assess self-efficacy for managing symptoms (v1.0), anxiety (v1.0), and depression (v1.0).9,24,62,63 For all PROMIS measures, the general population has a mean t-score of 50 with a SD of 10 points. For the PROMIS domain of self-efficacy for managing symptoms, a higher score indicates greater self-efficacy. For PROMIS domains assessing anxiety and depression, a lower score indicates lower anxiety and depression.

2.8.5. Performance-based function

Performance-based function tasks were completed in the following order: walking at a self-selected pace, walking at a quick standardized pace (Froude 471), heel raises, and hops. The order of starting with the right leg vs left leg for heel raises and hops was pseudorandomized, with participants who were assigned an odd-numbered study ID starting with the right side and those with an even-numbered study ID starting with the left side. The outcome assessor demonstrated each task along with verbal instructions. Participants were instructed to perform 2 practice trials on each side to become familiar with each task. The primary outcome was the maximum number of single-leg heel raises completed on the more painful side. Participants were instructed to “raise your heel up and down as high as possible, as many times as you can. Please try to keep your knee straight and your trunk upright. You can use this stool for fingertip balance as needed.” The activity was discontinued when the participant was unable to continue with good technique (knee bending, trunk flexion) or muscle fatigue. We selected the number of single-limb heel raises as our primary outcome of performance-based function because it is more feasible and translatable to a clinical setting compared with 3D motion analysis. For the hopping task, participants placed their hands on their lower rib cage to avoid momentum from swinging arms and were instructed to “step forward onto 1 leg, quickly bend your knee, and immediately jump upwards as high as possible.” Participants did 3 hops on each leg and the hop with the greatest height was used for analysis.

3D motion analysis was captured using a 12-camera system (Vicon Motion Systems of Centennial, CO and Los Angeles, CA) with a set of 57 reflective markers. Specific to the lower extremities, the kinematic model for each leg included 4 segments: pelvis, thigh, shank, and foot.71 Kinetic data were captured using 3 force plates embedded in the center of a 10-m walkway (AMTI, Inc, Watertown, MA). For walking, a minimum of 3 trials per side and per speed were averaged to create 1 representative trial. Ankle power was calculated using inverse dynamics as the product of the net ankle moment and ankle angular velocity. The ankle joint was defined using digitized points as the midpoint between the malleoli. Heel raise work was quantified as the sum of the change in ankle height times body weight for the maximum number of heel raises (n) that they were able to complete.40Heel raise work=i=1n[(change in height of malleolus)n×body weight]

The vertical jump test was used to quantify maximum jump height based on tracking of the lateral malleolus.58 Participants who were unable to hop were recorded as having a hop height of 0 cm and ankle power of 0 W/kg during hopping.

2D motion analysis was completed using video analysis (Kinovea, Version 0.8.15) for participants who completed evaluation visits virtually. Participants were instructed to make a mark on their lateral malleolus to facilitate tracking ankle motion. In addition, participants taking part in the study virtually mailed a tracing of their foot to the study team to allow foot length to be measured, which was entered into the 2D video analysis software to scale the image and allow for distance measurement. Performance-based function measures collected virtually included the number of heel raises and heel raise work.

2.8.6. Central nervous system nociceptive processing

The sensory testing protocol has been previously described in detail.47 Briefly, a pressure algometer (Somedic Algometer Type II, Horby Sweden, probe 1 cm2) was applied perpendicular to the skin at a rate of 50 kPa/second. Testing started on the left or right side, determined in a pseudorandomized manner using the same protocol as that for the performance-based tasks. Participants pressed a button when the sensation of pressure first became painful (>0/10) at the Achilles tendon and semitendinosus tendon on both legs. The mean of 3 trials per area represented the pressure pain threshold (PPT). The conditioning stimulus involved participants placing their hand in a cold (6 ± 0.5°C) water bath for 120 seconds and rating the pain in their hand (Numeric Pain Rating Scale [NRS]: 0-10) at 5 seconds and 20 seconds. The neutral stimulus involved participants placing their hand in a room temperature (22 ± 1.0°C) water bath for 120 seconds. The following formula was used to calculate the primary outcome of conditioned pain modulation (CPM) at the (more) involved side of the Achilles and at the semitendinosus tendon of the contralateral side:CPM=(PPT during conditioning stimulusPPT during room temperature water bathPPT during neutral stimulus)×100.

A higher CPM percentage represents a higher tolerance for pressure during the conditioning stimulus. We selected CPM at the Achilles tendon on the more painful side as the primary outcome of CNS nociceptive processing to replicate a study that had previously shown this to be impaired in the AT population.66 Several studies have reported a lack of impairment in CNS nociceptive processing in the AT population11,15,46; thus, we selected the sensory testing outcome most likely to detect impairment in this sample at baseline.66 As an indicator of widespread pain, the Collaborative Health Outcomes Information Registry (CHOIR) body map was used to quantify the number of areas with persistent or recurrent pain on a body map with 74 segments (range: 0-74).54 As an indicator of widespread symptoms, the Symptom Severity Scale was used to quantify the severity of fatigue, waking unrefreshed, cognitive symptoms, headaches, pain/cramps in abdomen, depression, and headache (range, 0-12).73

2.9. Treatment participation, fidelity assessment, and blinding

Participation was monitored by recording the number of sessions completed, percentage of home exercise completed on weekly log, average time spent on educational activities at home per week, and a knowledge assessment.

Fidelity in the delivery of the interventions was assessed by quantifying the duration of time spent with the participant during each treatment visit and the duration of time (in weeks) that was spent at each phase of the home exercise program. In addition, 8 weeks into the intervention, participants rated their level of therapeutic alliance with the physical therapist by answering 3 questions from the Working Alliance Inventory.25 The questions were rated on a 7-point scale from (0 = “Never” to 7 = “Always”): (1) “What I was doing in physical therapy gave me new ways of looking at my problem,” (2) “I was confident in [treating physical therapist]'s ability to help me,” (3) “[Treating physical therapist] and I were working towards mutually agreed upon goals.” In addition, 2 physical therapists who were not part of the study team listened to recordings of 10 visits and categorized participants into the presumed education group, rating their assessment on a scale of 0 (not confident at all) to 5 (completely confident).

To determine if participants were aware of the educational program they participated in, they answered the following question at 8 weeks: “At the beginning of the study, you were randomized to receive either Education A or Education B. We believe Education A is more helpful for recovery from Achilles tendinopathy than Education B. Which Education do you think that you received?” To assess blinding, the outcome assessor was asked, “Which educational treatment did the participant receive?” and “Why do you think the participant was in a particular group?”

2.10. Safety monitoring

Participants were asked about any injuries or changes in health at each visit by a physical therapist. Serious adverse events and unanticipated problems were addressed in consultation with the Safety Officer, a physician who was independent of the study team, and reported to the institutional review board. The Safety Officer, Data Safety and Monitoring Board, and study sponsor reviewed all adverse events (AEs), serious adverse events, and unanticipated problems. Adverse events were categorized as mild or moderate, depending on the diagnosis of specific symptom criteria as well as an evaluation of the severity and duration of symptoms. A mild AE had no impact or only a mild impact on participation in the study. A moderate AE impacted the participant's ability to take part in the evaluation (>50% of physical function measures were not captured due to AE) and/or treatment (exercise and/or education not progressed for >3 visits).

2.11. Data analyses

2.11.1. Participant enrollment and demographic variables at baseline

Descriptive statistics and group comparisons were used to describe demographic and clinical variables obtained at 0 weeks and to assess the effectiveness of randomizing participants to create equivalent groups. The normality of continuous variables was tested using Shapiro–Wilk tests and examined using the quantile–quantile plot. For continuous variables, the mean and SD or median and interquartile range were computed, and groups were compared using independent samples t-tests or Mann–Whitney tests, as appropriate based on distribution of data. For categorical variables, the frequency and percentages were calculated, and groups were compared using Fisher exact tests.

2.11.2. Linear mixed effects model for primary and secondary outcomes over time

We compared differences between groups for improvements in movement-evoked pain and self-reported function from 0 weeks (baseline) to 8 weeks (primary end point) and to 12 weeks using linear mixed models for repeated measures. The time variable included 2 time points (0 weeks and 8 weeks) for variables with laboratory-based measures (movement evoked pain, number of heal raises, CPM) and 3 time points (0 weeks, 8 weeks, and 12 weeks) for patient-reported outcomes (PROMIS-PF, TSK-17). Covariance types of compound symmetry, first-order autoregressive, and variance components were considered. Similarly, we used linear mixed models of repeated measures to assess an intervention effect within groups on performance-based function, psychosocial factors, and CNS nociceptive processing from 0 weeks to 8 weeks (primary end point) and to 12 weeks. We used an intention-to-treat analysis to examine the treatment effect for all outcome measures on participants based on group randomization. Secondary analyses on sex examined potential sex-based differences in outcomes to inform sample size estimates for future clinical trials. The analyses described above were expanded to explore the effect of sex as a fixed factor and examine interactions with group and time. Using the same data analysis strategy as described for sex, a secondary analysis on AT type (insertional vs midportion) was also completed to inform recruitment strategies for future clinical trials.

2.11.3. Multivariable linear regression of factors associated with improvement in pain and function

An exploratory analysis examined if baseline value or changes in knowledge (total, pathoanatomical knowledge subscore, pain science knowledge subscore), performance-based function (number of heel raises), psychosocial factors (TSK-17, PCS-13, PROMIS Self-efficacy), CNS nociceptive processing (CPM at the Achilles, temporal summation, PPT at the Achilles), and demographics (sex, age, body mass index, AT type) were associated with the change in pain (movement-evoked pain during single leg heel raises) and/or function (VISA-A). Educational group (PSE vs PAE) as well as baseline values for pain and function were included in the regression models for change in pain and change in function, respectively. We first examined Pearson correlation coefficients between each variable with pain and function individually. Correlations with r of ≥0.3 were considered in the linear multivariable regression model to predict change in pain and function from 0 to 8 weeks.

2.11.4. Post hoc subgroup analysis of individuals with elevated kinesiophobia

Among only individuals with elevated kinesiophobia (TSK-17 > 37), we examined if PSE plus exercise was more effective than PAE plus exercise in patients with chronic AT. To parallel the primary analysis, we used 2-way mixed effects analysis of variances (random effect: baseline, 8 weeks; fixed effect: PSE, PAE) to examine the effects on the primary outcomes for pain, self-reported function, performance-based function, psychosocial factors, and CNS nociceptive processing.

2.12. Individual participant data sharing plan

In compliance with Findability, Accessible, Interoperability, and Reusability (FAIR) data principles, data for the primary and secondary outcomes reported in this article were deposited in the University of Iowa open-access institutional repository, Iowa Research Online.72 The repository is open access and maintained by the Libraries at the University of Iowa for the preservation and sharing of intellectual work of faculty, students, and staff. The data sets are accompanied with appropriate descriptive metadata to facilitate discovery and scholarly reuse. The data is available at https://doi.org/10.25820/data.006166.

3. Results

3.1. Participant enrollment and demographic variables at baseline

Participants were enrolled over a 16-month period between September 2019 and December 2020. All study outcomes were completed by March 2021. Of the 313 individuals screened, 145 were excluded because they did not meet the eligibility criteria and 75 were eligible but did not sign consent due to the participant not responding to our follow-up emails and/or phone calls (45) or declined participation (30) (Fig. 1). Ninety-three individuals provided consent to participate in the study, and 27 of these were excluded following additional review of eligibility criteria at the first evaluation visit. A total of 66 participants were randomized to either the PSE plus exercise group or the PAE plus exercise group. One participant in the PAE group dropped out of the study after 2 treatment visits due to an unrelated health problem.

The demographic and clinical variables were similar between groups prior to randomization (Table 2). The majority of participants had AT pain for at least 1 year, had sought care from at least 2 healthcare providers for AT symptoms, and had previously tried at least 5 different treatments for AT (Table 2). Prior exposure to pain education was uncommon in this sample with 1 participant in the PSE group reporting this in their treatment history (Table 2). On average, both groups had elevated kinesiophobia at baseline (TSK-17: PSE = 37.2 ± 6.2, PAE = 37.7 ± 5.2, Table 3).

Table 2 - Participant demographic information and treatment history reported at baseline for the pain science education and pathoanatomical education groups.
Pain science education (n = 33) Pathoanatomical education (n = 33) P
Age, y 41.8 ± 14.9 44.9 ± 16.1 0.425
Sex
 Female 57.6% (19) 54.5% (18) 0.804
 Male 42.4% (14) 45.5% (15)
AT type
 Insertional 54.5% (18) 57.6% (19) 0.694
 Midportion 45.5% (15) 42.4% (14)
Body mass index 28.2 [21.0-35.3] 28.5 [20.4-36.1] 0.798
Pain duration (mo) 14.0 [7.0-36.0] 18.0 [11.5-36.0] 0.817
Ethnicity
 Hispanic, Latino, or Spanish 6.0% (2) 3.0% (1) 0.558
Race
 Caucasian 84.8% (27) 93.9% (29)
 Black/African American 6.0% (2) 6.1% (2) 0.492
 Asian 6.0% (2) 0.0% (0)
 American Indian/Alaska Native 0.0% (0) 3.0% (1)
 Hispanic/Latino 6.0% (2) 3.0% (1)
Education
 High school diploma/GED 3.0% (1) 3.0% (1)
 Some college or a vocation/technical certificate 18.2% (6) 21.2% (7) 0.753
 Bachelor's degree 33.3% (11) 39.4% (13)
 Advanced/professional degree 45.5% (15) 36.4% (12)
Number of providers sought for AT 2.0 [1.0-2.5] 2.0 [1.0-3.0] 0.995
Providers sought for AT
 Physical therapist 57.6% (19) 54.5% (18)
 Primary care physician 39.4% (13) 42.4% (14)
 Orthopedic surgeon 12.1% (4) 18.2% (6)
 Sports medicine physician 21.2% (7) 21.2% (7)
 Podiatrist 6.1% (2) 18.2% (6)
 Chiropractor 6.1% (2) 18.2% (6)
 Other (massage therapy, acupuncturist, osteopath, athletic trainer, complimentary and alternative medicine) 15.2% (5) 6.0% (2)
Number of previous treatments tried 5.0 [4.0-7.0] 5.0 [3.0-6.5] 0.698
Treatments tried prior
 Strengthening exercises 69.7% (23) 60.6% (20)
 Stretching 81.8% (27) 92.9% (31)
 Ice 69.7% (23) 60.6 (19)
 Oral pain medication (eg, NSAIDS) 48.5% (16) 57.6% (19)
 Massage/soft tissue techniques 48.5% (16) 45.5% (15)
 Heel lifts 42.4% (14) 48.5% (16)
 Manual therapy 24.2% (8) 27.3% (9)
 Taping 39.4% (13) 18.2% (6)
 Foot orthotics 36.4% (12) 33.3% (11)
 Night splints 9.1% (3) 18.2% (6)
 Instrument assisted soft tissue mobilization 18.2% (6) 3.0% (1)
 Pain neurophysiology/psychology education 3.0% (1) 0.0% (0)
 Extracorporeal shockwave therapy 9.1% (3) 3.0% (1)
 Injections (PRP, sclerosing therapy, prolotherapy, corticosteroids) 6.1% (2) 6.1% (2)
 Other (laser therapy, alternative running techniques, dry needling) 27.3% (9) 27.3% (9)
Normally distributed data are presented as mean ± standard deviation, categorical data are presented as percent of sample (n), and data that are not normally distributed are presented as median [interquartile range].
GED, general education development; NSAIDS, nonsteroidal anti-inflammatory drugs; PRP, platelet-rich plasma.

Table 3 - Primary (*) and secondary outcomes at each timepoint by group are presented as mean ± standard deviation and (95% confidence interval).
Variable Grp 0 wk 8 wk 12 wk P
Grp Time
AT symptoms
 *Pain during heel raises (0-10) PSE
n = 33
4.9 ± 2.3 (4.0-5.7) 1.8 ± 1.8 (1.2-2.5) N/A 0.971 <0.001
PAE
n = 33
5.2 ± 1.9 (4.5-5.8) 1.5±1.6 (1.0-2.1) N/A
 Pain during hops (0-10) PSE
n = 26
4.1 ± 2.1 (3.2-5.0) 1.4 ± 1.4 (0.8-1.9) N/A 0.917 <0.001
PAE
n = 27
4.5 ± 2.1 (3.6-5.4) 1.1 ± 1.3 (0.5-1.6) N/A
 Expected pain during heel raises (0-100) PSE
n = 33
46.4 ± 20.6 (39.1-53.7) 20.9 ± 16.0 (15.2-26.6) 16.2 ± 17.7 (9.9-22.5) 0.770 <0.001
PAE
n = 33
50.5 ± 21.3 (42.9-58.0) 18.7 ± 16.4 (12.7-24.6) 10.8 ± 13.7 (5.8-15.7)
 Expected pain during hops (0-100) PSE
n = 33
52.6 ± 21.0 (45.2-60.1) 31.6 ± 23.9 (23.1-40.1) 26.6 ± 24.5 (17.9-35.3) 0.290 <0.001
PAE
n = 33
59.2 ± 21.7 (51.5-66.9) 33.4 ± 24.5 (24.6-42.2) 24.0 ± 26.0 (14.6-33.4)
 Average duration of tendon stiffness (0 to >100 min) PSE
n = 33
34.9 ± 28.2 (24.9-44.9) 12.3 ± 11.8 (8.1-16.5) 9.0 ± 11.8 (4.8-13.2) 0.335 <0.001
PAE
n = 33
28.8 ± 18.4 (22.2-35.3) 12.1 ± 12.1 (7.7-16.5) 8.6 ± 8.0 (5.7-11.4)
Self-reported function
 *PROMIS physical function PSE
n = 33
49.3 ± 7.4 (46.7-51.9) 51.0 ± 7.8 (48.2-53.7) 52.4 ± 7.8 (49.6-55.2) 0.228 0.072
PAE
n = 33
47.3 ± 6.0 (45.2-49.4) 50.1 ± 6.3 (47.8-52.4) 51.2 ± 7.2 (48.6-53.8)
 VISA-A PSE
n = 33
44.5 ± 16.4 (38.6-50.3) 63.1 ± 17.8 (56.8-69.4) 67.7 ± 19.7 (60.6-74.8) 0.434 <0.001
PAE
n = 33
44.3 ± 17.5 (38.1-50.5) 58.5 ± 17.5 (52.2-64.8) 64.5 ± 20.4 (57.1-72.0)
Performance-based function
 *Number of single-limb heel raises PSE
n = 33
15.0 ± 8.5 (12.0-18.0) 22.3 ± 10.2 (18.7-25.9) N/A 0.622 0.006
PAE
n = 33
18.1 ± 13.0 (13.4-22.8) 21.1 ± 10.6 (17.2-24.9) N/A
 Heel raise work (N·m) PSE
n = 33
619.4 ± 365.7 (487.6-751.3) 914.5 ± 447.5 (750.4-1078.7) N/A 0.086 0.008
PAE
n = 33
834.1 ± 518.3 (644.0-1024.2) 980.5 ± 479.3 (804.7-1156.3) N/A
 Hop height (cm) PSE
n = 20
12.2 ± 8.6 (8.1-16.3) 15.0 ± 7.2 (11.2-18.9) N/A 0.065 0.099
PAE
n = 25
8.1 ± 9.7 (3.9-12.2) 11.8 ± 8.5 (7.5-16.2) N/A
 Ankle power during walking at self-selected speed (W/kg) PSE
n = 20
2.5 ± 1.2 (1.9-3.1) 2.3 ± 0.6 (2.0-2.7) N/A 0.680 0.230
PAE
n = 25
2.0 ± 0.6 (1.8-2.3) 2.7 ± 0.8 (2.3-3.1) N/A
 Ankle power during walking at standardized speed (W/kg) PSE
n = 20
3.2 ± 0.8 (2.8-3.7) 3.1 ± 0.8 (2.7-3.5) N/A 0.658 0.419
PAE
n = 25
3.0 ± 1.0 (2.6-3.5) 3.5 ± 0.9 (3.0-3.9) N/A
 Ankle power during hopping (W/kg) PSE
n = 20
6.2 ± 4.5 (4.0-8.4) 7.0 ± 3.3 (5.3-8.8) N/A 0.106 0.152
PAE
n = 25
4.0 ± 4.9 (1.9-6.1) 6.1 ± 4.5 (3.7-8.4) N/A
Psychosocial factors
 *TSK PSE
n = 33
37.2 ± 6.2 (35.0-39.3) 29.4 ± 6.5 (27.1-31.7) 29.8 ± 7.4 (27.1-32.4) 0.077 <0.001
PAE
n = 33
37.7 ± 5.2 (35.9-39.6) 32.6 ± 6.1 (30.4-34.8) 32.3 ± 6.1 (30.0-34.5)
 PCS PSE
n = 33
11.7 ± 7.5 (9.1-14.4) 6.1 ± 6.2 (3.9-8.3) 6.9 ± 8.2 (4.0-9.9) 0.350 <0.001
PAE
n = 33
10.2 ± 6.3 (8.0-12.5) 5.5 ± 5.3 (3.6-7.4) 4.8 ± 6.0 (2.6-7.0)
 PROMIS pain self-efficacy PSE
n = 33
46.8 ± 6.4 (44.5-49.1) 52.4 ± 8.2 (49.5-55.3) 53.0 ± 9.8 (49.4-56.5) 0.885 <0.001
PAE
n = 33
46.6 ± 6.6 (44.2-48.9) 52.3 ± 8.3 (49.3-55.3) 54.1 ± 8.8 (50.9-57.4)
 PROMIS anxiety PSE
n = 33
54.2 ± 8.2 (51.2-57.1) 53.3 ± 8.2 (50.4-56.2) 53.7 ± 8.3 (50.7-56.7) 0.476 0.130
PAE
n = 33
54.6 ± 10.0 (51.0-58.1) 50.6 ± 10.0 (46.9-54.2) 49.4 ± 10.1 (45.7-53.2)
 PROMIS depression PSE
n = 33
47.9 ± 8.4 (44.9-50.9) 47.6 ± 8.4 (44.6-50.6) 49.6 ± 7.2 (47.0-52.2) 0.913 0.701
PAE
n = 33
48.0 ± 7.6 (45.3-50.7) 47.2 ± 8.5 (44.1-50.3) 46.4 ± 8.0 (43.5-49.3)
CNS nociceptive processing
 *CPM at Achilles tendon PSE
n = 25
24.0 ± 34.0 (8.1-39.9) 16.6 ± 17.4 (7.7-25.5) N/A 0.899 0.057
PAE
n = 25
28.1 ± 28.8 (16.0-40.3) 13.3 ± 20.0 (3.7-22.9) N/A
 CPM at semitendinosis tendon PSE
n = 25
27.4 ± 33.6 (11.6-43.1) 14.2 ± 26.1 (0.7-27.6) N/A 0.947 0.118
PAE
n = 25
24.4 ± 26.3 (13.0-35.7) 16.9 ± 27.3 (3.3-30.5) N/A
 Temporal summation PSE
n = 25
2.1 ± 1.3 (1.5-2.7) 1.9 ± 1.6 (1.1-2.7) N/A 0.900 0.741
PAE
n = 25
2.1 ± 1.4 (1.5-2.7) 2.0 ± 1.2 (1.5 ± 2.6) N/A
 PPT at Achilles on involved side PSE
n = 25
476.6 ± 212.5 (377.1-576.0) 477.0 ± 152.1 (398.8-555.2) N/A 0.372 0.537
PAE
n = 25
415.1 ± 171.4 (344.4-485.9) 465.1 ± 242.8 (348.1-582.2) N/A
 PPT at Achilles on uninvolved side PSE
n = 25
529.9 ± 202.9 (434.9-624.8) 535.0 ± 214.3 (424.8-645.2) N/A 0.806 0.748
PAE
n = 25
560.8 ± 262.0 (452.7-669.0) 525.3 ± 242.1 (408.6-642.0) N/A
 CHOIR body map PSE
n = 33
5.1 ± 4.5 (3.5-6.7) 4.6 ± 5.5 (2.6-6.5) 4.1 ± 3.6 (2.8-5.4) 0.429 0.256
PAE
n = 33
4.8 ± 4.5 (3.3-6.4) 3.5 ± 3.3 (2.3-4.7) 3.5 ± 3.4 (2.3-4.8)
 Symptom Severity Score PSE
n = 33
4.3 ± 2.4 (3.4-5.2) 3.4 ± 2.2 (2.6-4.2) 3.3 ± 2.3 (2.4-4.1) 0.452 0.046
PAE
n = 33
4.6 ± 3.0 (3.6-5.7) 3.7 ± 2.4 (2.8-4.6) 3.3 ± 2.5 (2.4-4.2)
P value for time is for the change by 8 week (primary end point). Uncorrected P values are presented. Bonferroni correction for between-group comparison of AT pain and function is P = 0.025. Bonferroni correction for over time comparison (0- to 8-week time point) for performance-based function, psychosocial factors, and central nervous system (CNS) nociceptive processing is P = 0.017.
AT, Achilles tendinopathy; CHOIR, Collaborative Health Outcomes Information Registry body map; CNS, central nervous system; GROC, global rating of change; MCID, minimal clinically important difference; PAE, pathoanatomical education; PROMIS, Patient-Reported Outcomes Measurement Information System; PSE, pain science education; VISA-A, Victorian Institute of Sport Assessment- Achilles. Statistically significant p-values in bold.

3.2. Pain and self-reported function

The PSE plus exercise program was not more effective than the placebo education (ie, PAE) plus exercise on outcomes of pain or self-reported function (Table 3). Both groups had a decrease in primary (decrease in movement-evoked pain during HR: PSE = −3.0, 95% CI of the difference = −3.8 to −2.2, PAE = −3.6, 95% CI = −4.4 to −2.8) and secondary outcomes of AT symptoms by 8 weeks (P > 0.05 for effect of education group on pain and all secondary AT symptom outcomes, Table 3, Fig. 3). Secondary outcomes of AT symptoms indicate a maintenance of improvement at 12 weeks (Table 3). Neither group had an increase in function with primary outcome for self-reported function (change in PROMIS Physical Function, PSE: 8 weeks = 1.8, 95% CI = 0.3-3.4, 12 weeks = 3.3, 95% CI = 1.7-4.8; PAE: 8 weeks = 2.5, 95% CI = 0.8-4.2, 12 weeks = 3.7, 95% CI = 1.4-5.9). The secondary outcome for self-reported function indicates that both groups demonstrated improved Achilles tendon function by 8 weeks that was maintained at 12 weeks (change in VISA-A, PSE: 8 weeks = 18.8, 95% CI = 13.5-24.1, 12 weeks = 23.4, 95% CI = 17.1-29.7; PAE: 8-weeks = 14.5, 95% CI = 8.7-20.3, 12 weeks = 20.0, 95% CI = 13.6-26.3). There were no differences in pain or function between men and women or between participants with midportion or insertional AT (P > 0.05 for all effects of sex and AT type).

F3
Figure 3.:
Changes in (A) pain, (B) self-reported function, and (C) fear of movement with the Tampa Scale of Kinesiophobia (TSK-17), (D) performance-based function with the maximum number of single-leg heel raises, and (E) central nervous system processing of nociceptive input with conditioned pain modulation (CPM) over time and by group (pathoanatomical education [PAE], pain science education [PSE]). Statistically significant improvements over time are indicated by bars with an asterisk (*). PROMIS, Patient-Reported Outcomes Measurement Information System.

3.3. Performance-based function

The primary outcome for performance-based function improved by 8 weeks (increase in number of single limb heel raises: 5.2, 95% CI: 1.6-8.8, Fig. 3). The secondary outcome of heel raise work also improved (217.6 N·m, 95% CI: 71.4-363.8), but there were no improvements in hop height or peak ankle power during walking or hopping (Table 3). We detected a statistically significant effect of sex on heel rise work with men, demonstrating greater heel rise work than women (mean difference = 370.9, 95% CI [223.1-518.7]). There were no other effects of education group, AT type, or sex on primary and secondary performance-based function measures (P > 0.05 for all comparisons).

3.4. Psychosocial factors

The primary outcome of fear of movement decreased by 8 weeks (TSK-17: −6.5, 95% CI: −4.3 to −8.7), and the improvement was maintained at 12-week follow-up (Table 3, Fig. 3). Secondary outcomes of the Pain Catastrophizing Scale (PCS) and PROMIS Self-efficacy of Managing Symptoms improved (Table 3). There were no changes in PROMIS Anxiety or PROMIS Depression over time (Table 3). We detected a statistically significant effect of sex on pain catastrophizing with men reporting a higher PCS score compared with women (mean difference = 4.1, 95% CI [2.0-6.2]). There were no other effects of education group, AT type, or sex on primary or secondary psychosocial factors (P > 0.05 for all comparisons).

3.5. Central nervous system nociceptive processing

The primary outcome of CPM at the Achilles tendon on the involved side did not change by 8 weeks (−11.4%, 95% CI: 0.2 to −17.3). Secondary outcomes for CNS nociceptive processing did not change over time (P > 0.05 for effect of time, Table 3, Fig. 3). There was an effect of AT type on the PPT at the Achilles tendon on the uninvolved side with the participants who had midportion AT, demonstrating a lower PPT at the Achilles tendon on the contralateral side compared with those with insertional AT at baseline (midportion AT: 452.1, 95% CI = 183.2-281.0, insertional AT: 623.1, 95% CI = 213.8-380.8, P = 0.009). There were no other effects of education group, AT type, or sex on primary or secondary measures for CNS nociceptive processing (P > 0.05 for all comparisons).

3.6. Factors associated with improvement in pain and function

To examine contributors to improvement in movement-evoked pain and disability, we performed a multivariate linear regression. Model 1 explained 58.1% of the variance in the improvement of movement-evoked pain from 0 to 8 weeks; a higher baseline movement-evoked pain and a greater increase in PROMIS Self-efficacy were associated with a greater reduction in movement-evoked pain (Table 4). For every 10-point increase in self-efficacy, there was a 0.6-point reduction in movement-evoked pain. Model 2 explained 39.4% of the variance in the improvement in the VISA-A from 0 to 8 weeks; a higher level of function at baseline and a greater increase in knowledge were associated with a greater increase in VISA-A (Table 4). For every 1-point increase on the total knowledge score, there was a 3.9-point increase in self-reported function on the VISA-A. Although included in both models, there was no significant effect of group on improvement in pain or function. Sex and AT type were not associated with improvement in pain or function and were not included in either model.

Table 4 - Factors associated with improvement in pain and function from 0 to 8 weeks within multivariate regression models.
Factor β (95% CI) P
Model 1: change in movement-evoked pain, r2 = 0.581
 Movement-evoked pain at baseline −0.761 (−0.581 to −0.941) <0.001
 Pain education group −0.380 (−1.133 to 0.373) 0.327
 Change in PROMIS self-efficacy −0.057 (−0.099 to −0.015) 0.009
Model 2: change in VISA-A, r2 = 0.394
 VISA-A at baseline −0.541 (−0.757 to −0.325) <0.001
 Pain education group 7.363 (−0.070 to 14.796) 0.057
 Change in total knowledge score 3.871 (1.678 to 6.064) 0.001
Statistically significant p-values in bold. 95 % CI, 95% confidence interval; PROMIS, Patient-Reported Outcomes Measurement Information System; VISA-A, Victorian Institute of Sport Assessment-Achilles.

3.7. Post hoc subgroup analysis of individuals with elevated kinesiophobia

Considering only participants with elevated kinesiophobia at baseline (PSE: n = 17; PAE: n = 19), the PSE plus exercise program was not more effective than the placebo education ie, (PAE) plus exercise on outcomes of pain, self-reported function, performance-based function, psychosocial factors, or CNS nociceptive processing (Table 5).

Table 5 - Primary outcomes for self-reported function at the primary end point by group are presented as mean ± standard deviation and (95% confidence interval).
Variable Grp 0 wk 8 wk P
Grp Time Grp × Time
AT symptoms
 Pain during heel raises (0-10) PSE
n = 17
5.2 ± 2.0 (4.2-6.1) 2.1 ± 1.4 (1.4-2.7) 0.337 <0.001 0.250
PAE
n = 19
5.2 ± 1.9 (4.3-6.1) 1.2 ± 1.4 (0.6-1.9)
Self-reported function
 PROMIS physical function PSE
n = 17
45.9 ± 5.9 (42.8-49.1) 48.7 ± 7.4 (47.1-53.8) 0.451 <0.001 0.952
PAE
n = 19
47.5 ± 6.8 (44.3-50.5) 50.4 ± 7.1 (45.2-52.3)
Performance-based function
 Number of single-limb heel raises PSE
n = 17
15.1 ± 8.6 (9.8-20.4) 22.2 ± 11.0 (17.4-27.5) 0.748 <0.001 0.626
PAE
n = 19
17.0 ± 12.2 (12.0-21.9) 22.4 ± 10.6 (17.4-27.5)
Psychosocial factors
 TSK PSE
n = 17
41.9 ± 4.1 (40.3-43.6) 32.4 ± 6.5 (29.4-35.4) 0.495 <0.001 0.052
PAE
n = 19
41.2 ± 2.3 (39.6-42.7) 35.1 ± 5.7 (32.3-37.9)
CNS nociceptive processing
 CPM at Achilles tendon PSE
n = 7
31.2 ± 31.3 (8.1-39.9) 18.8 ± 17.8 (7.7-25.5) 0.316 0.322 0.810
PAE
n = 10
21.6± 27.3 (3.6-5.7) 14.0 ± 17.8 (2.8-4.6)
AT, Achilles tendinopathy; CHOIR, Collaborative Health Outcomes Information Registry body map; CNS, central nervous system; GROC, global rating of change; MCID, minimal clinically important difference; PAE, pathoanatomical education; PROMIS, Patient-Reported Outcomes Measurement Information System; PSE, pain science education; VISA-A, Victorian Institute of Sport Assessment-Achilles. Statistically significant p-values in bold.

3.8. Participant, treatment fidelity, and blinding

Participants in both groups completed at least 6 treatment visits, reported more than 90% adherence to exercise program, and spent 15 to 30 minutes each week completing education homework (Table 6). At 0 weeks, both groups had equivalent knowledge assessment scores. At 8 weeks, each group had a higher subscore specific to their educational group (Table 6). For treatment fidelity, both groups spent 35 to 40 minutes with the physical therapist at each visit and progressed at a similar rate through the exercise program (Table 6). Both groups reported a high level of therapeutic alliance with the treating physical therapist (Table 6).

Table 6 - Participation, treatment fidelity, and blinding for the pain science education and pathoanatomical education groups.
Pain science education Pathoanatomical education P
Participation
 Follow-up visits completed (#) 6.0 [6.0-7.0] 7.0 [6.0-7.0] 0.097
 Percentage of home exercise program completed (%) 92.1 ± 10.4 91.5 ± 11.1 0.525
 Time spent on educational activities at home (min) 20.0 [15.0-30.0] 17.5 [15.0-30.0] 0.963
 0-wk knowledge assessment
  Total score 4.0 [3.5-6.0] 5.0 [4.0-6.0] 0.440
  Pathoanatomical subscore 1.0 [1.0-2.0] 2.0 [1.0-2.0] 0.150
  Pain education subscore 3.0 [2.0-3.0] 2.0 [2.0-3.0] 0.084
  Activity guidelines subscore 1.0 [0.0-1.0] 1.0 [0.5-1.0] 0.120
 8-wk knowledge assessment
  Total score 7.0 [6.0-7.5] 8.0 [7.0-8.0] 0.004
  Pathoanatomical subscore 2.0 [1.0-3.0] 3.0 [3.0-4.0] <0.001
  Pain education subscore 4.0 [3.0-4.0] 3.0 [3.0-4.0] 0.001
  Activity guidelines subscore 1.0 [1.0-1.0] 1.0 [1.0-1.0] 1.000
Treatment Fidelity
 Time with patient per visit (min) 38.4 [34.9-42.3] 35.5 [29.7-40.8] 0.071
 Week initiated isometric phase 0.0 [0.0-0.0] 0.0 [0.0-0.0] 1.000
  Week 0: % (n) 100.0 (33) 100.0 (33) 1.000
   # of sets
 Duration of hold (s)
5.0 [5.0-5.0]
20.0 [10.0-30.0]
5.0 [5.0-5.0]
20.0 [10.0-20.0]
  Week 1: % (n) 87.8 (29) 93.9 (31) 0.230
   # of sets
 Duration of hold (s)
5.0 [5.0-5.0]
30.0 [20.0-45.0]
5.0 [5.0-5.0]
45.0 [25.0-45.0]
  Week 2: % (n) 63.6 (21) 56.3 (18) 0.453
   # of sets
 Duration of hold (s)
5.0 [5.0-5.0]
45.0 [30.0-45.0]
5.0 [5.0-5.0]
45.0 [45.0-45.0]
  Week 3: % (n) 18.2 (6) 21.9 (7) 0.710
   # of sets
 Duration of hold (s)
5.0 [5.0-5.0]
45.0 [45.0-45.0]
5.0 [5.0-5.0]
45.0 [45.0-45.0]
  Week 4: % (n) 0.0 (0) 9.4 (3) 0.072
   # of sets
 Duration of hold (s)
0.0 [0.0-0.0]
0.0 [0.0-0.0]
5.0 [5.0-5.0]
30.0 [20.0-37.5]
 Week initiated heel raise phase 3.0 [2.0-3.0] 3.0 [2.0-3.0] 0.983
  Week 1: % (n) 12.1 (4) 6.3 (2) 0.414
   # of sets
 # Repetitions
3.0 [3.0-3.0]
15.0 [15.0-15.0]
3.0 [3.0-3.0]
15.0 [15.0-15.0]
  Week 2: % (n) 36.4 (12) 43.8 (14) 0.543
   # of sets
 # Repetitions
3.0 [3.0-3.0]
15.0 [15.0-15.0]
3.0 [3.0-3.0]
15.0 [15.0-15.0]
  Week 3: % (n) 72.7 (24) 75.0 (24) 0.835
   # of sets
 # Repetitions
3.0 [3.0-3.0]
15.0 [15.0-15.0]
3.0 [3.0-3.0]
15.0 [10.0-15.0]
  Week 4: % (n) 81.8 (27) 71.9 (23) 0.341
   # of sets
 # Repetitions
3.0 [3.0-3.0]
15.0 [15.0-15.0]
3.0 [3.0-3.0]
15.0 [15.0-15.0]
  Week 5: % (n) 63.6 (21) 68.8 (22) 0.663
   # of sets
 # Repetitions
3.0 [3.0-3.0]
15.0 [15.0-15.0]
3.0 [3.0-3.0]
15.0 [15.0-15.0]
 Week initiated spring phase
 (N = # not initiated in first 7 wk)
5.0 [4.0-5.0]
20 (60.6%)
4.5 [4.0-5.0]
20 (62.5%)
0.979
  Week 3 (stairs): % (n) 9.1 (3) 3.1 (1) 0.317
   # flights (stairs) 4.0 [3.5-4.5] 4.0 [4.0-4.0]
  Week 4 (stairs): % (n) 12.1 (4) 15.6 (5) 0.683
   # flights (stairs) 7.5 [4.5-10.0] 3.0 [3.0-4.0]
  Week 4 (hopping): % (n) 6.1 (2) 3.1 (1) 0.573
   # of sets
 Duration of hopping (s)
3.0 [3.0-3.0]
20.0 [20.0-20.0]
3.0 [3.0-3.0]
20.0 [20.0-20.0]
  Week 5 (stairs): % (n) 21.2 (7) 25 (8) 0.717
   # flights (stairs) 3.0 [3.0-3.0] 4.5 [3.0-10.0]
  Week 5 (hopping): % (n) 15.2 (5) 6.3 (2) 0.975
   # of sets
 Duration of hopping (s)
3.0 [3.0-3.0]
20.0 [20.0-20.0]
3.0 [3.0-3.0]
20.0 [20.0-20.0]
Therapeutic alliance
 What I was doing in physical therapy gave me new ways of looking at my problem 6.0 [5.0-6.5] 5.5 [5.0-6.8] 0.673
 I was confident in my PT's ability to help me 7.0 [ 6.0-7.0] 7.0 [7.0-7.0] 0.436
 My PT and I were working towards mutually agreed upon goals 7.0 [7.0-7.0] 7.0 [7.0-7.0] 0.347
Independent rater identification of treatment group (# correct/# sessions reviewed) 8/10 9/10
Blinding
 Participant believed they were in experimental group A
  Yes 57.6% (19/33) 53.1% (17/32)
  No 3.0% (1/33) 0.0% (0/32)
  Not sure 39.4% (13/33) 46.9% (15/32)
 Participant correct Identification of treatment group (% correct) 57.6% (19/33) 0% (0/33)
 Outcome assessor identification of treatment group (% correct)
  Pain education 9.1% (3) 3.0% (1)
  Pathoanatomical education 3.0% (1) 9.1% (3)
  Do not know 87.9% (29) 84.8% (28)
PT, physical therapist. Statistically significant p-values in bold.

Two independent raters reviewed audio recordings. These raters correctly identified participant-assigned groups in 8/10 (PSE) and 9/10 (PAE) cases, with a median confidence rating of 5/5 and 4/5, respectively. However, fidelity was compromised at 1 session; both raters thought that the PSE addressing kinesiophobia at visit 2 was the PAE at visit 2. The raters reported that they based their judgement on the provision of information on how exercise strengthens the tendon's capacity for loading. One rater thought that the pathoanatomical education group was the pain science education group at visit 6. This session provides information on the benefits of exercise for multiple body systems, including the immune system.

More than half of the participants in both groups believed that they received the education program that the study team thought was most effective (Table 6). Thus, 57.6% of those in the PSE group and 0.0% of those in the PAE group correctly identified their group allocation. The outcome assessor was most commonly (84.8%-87.9%) unsure of group allocation at the 8-week evaluation visit, correctly determined the group allocation for 6 participants (3 in each group), and incorrectly identified group allocation for 2 participants (1 in each group).

3.9. Global rating of change

There were no differences between educational groups in global rating of change at any time point (P = 0.179). At baseline, both groups anticipated that after 12 weeks, their tendon health would be “moderately better” (PSE: 4.1 ± 2.1, PAE: 4.7 ± 1.8). After treatment, both groups reported their tendon health to be “moderately better” to “quite a bit better” (8 weeks: PSE: 4.6 ± 1.7, PAE: 5.3 ± 1.7; 12 weeks: PSE: 5.0 ± 2.4, PAE: 5.5 ± 2.0). By 8 weeks, 51 participants reported at least a moderate improvement (score > 4) and 14 participants reported that the overall condition of their tendon was a “a tiny bit better” to “a little bit better.” There was no effect of AT type (P = 0.271) or sex (P = 0.143) on global rating of change.

3.10. Safety monitoring

Over the 12-week study period, 28 participants had AEs. Among these AE, 26 were mild and 2 were moderate. Most of the mild AEs (10/26) were a temporary increase in AT pain with activity. One moderate AE was a change in health, unrelated to study participation, that resulted in a patient withdrawing from the study. The second moderate AE was possibly related to study participation and was an unanticipated problem. Specifically, the participant ruptured their plantar fascia while walking 1 week after enrolling in the study. One month prior to enrolling in the study, this participant had a corticosteroid injection of the plantar fascia on the leg that had the subsequent rupture. The participant was enrolled for AT pain on the contralateral leg without the plantar fascia rupture. The participant remained in the study with exercises modified to accommodate the use of a boot on the contralateral leg. In consultation with the Safety Officer, the DSMB, the IRB, and study sponsor, the study exclusion criteria were subsequently updated to include a history of corticosteroid injection to the foot, ankle, or legs within the past 3 months.

4. Discussion

4.1. Summary of findings

The first objective of this RCT was to determine if an exercise program plus PSE was more effective at reducing pain and improving function than PAE in patients with chronic AT. Contrary to our hypothesis, there were no differences between groups on our primary outcomes at 8 weeks nor at 12-week follow-up. Aspects of the treatment that were common to both groups may have outweighed the effect of education, including evidence-based education, >90% adherence to a high-quality exercise program, and a high therapeutic alliance with the physical therapist. Moreover, the progressive tendon loading program used in the current study is similar to a graded exposure approach to exercise,68 which may have contributed to the improvement in pain-related psychological factors in the PAE group despite the lack of PSE education.

The second objective was to determine the magnitude of change in pain-related factors with an exercise program regardless of education type. Our hypotheses were partially supported with improvement in performance-based function and psychosocial factors, but CNS nociceptive processing did not improve. Participants with AT demonstrated CPM and temporal summation at similar magnitude as previously reported controls,11 which may have contributed to the lack of improvement over time. In addition, due to COVID-19 restrictions on in-person research, sensory testing data are missing for 16 participants, resulting in a lack of statistical power to detect small to medium effect sizes over time.

4.2. Comparison to other studies

4.2.1. Mechanisms of improvement in pain and function

This is the first adequately placebo-controlled RCT to compare the effect of adding PSE to a best practice exercise program for a chronic musculoskeletal condition.56 In addition to baseline levels of pain and function, we found that a greater increase self-efficacy and a greater increase in knowledge gain were associated with a greater reduction in pain and increase in function, respectively. In contrast, the type of education was not associated with the magnitude of improvement. Together this implies that learning something new may be more influential than the educational content on treatment outcomes. Distinct treatment approaches may share common psychosocial mechanisms, such as improved self-efficacy in management of symptoms. Smeets et al.60 demonstrated that pain catastrophizing was a key mediator of improvement in pain and function across exercise, cognitive-behavioral therapy, and exercise plus cognitive behavioral therapy for chronic low back pain. More research is needed to better understand mediating factors that contribute to nonspecific effects of seemingly contrasting therapeutic approaches.

4.2.2. Efficacy of education and exercise for Achilles tendinopathy pain and function

The education and exercise programs were effective and feasible with 65 of 66 participants completing all visits, 90% adherence rate to the home exercise program, and less than 30 minutes of educational homework per week. The participants enrolled in this study were comparable to the samples of other RCTs examining the efficacy of exercise without a structured education component,3,29,50,59,61 except that our sample included patients with either insertional or midportion AT, although previous studies have examined these AT subtypes separately. These previous RCTs have reported a clinically meaningful reduction in pain (−1.8 to −2.6 on 11-point NRS) and improvement in self-reported function (15.4-22-point improvement in the VISA-A) with exercise.3,29,50,59,61 Similarly, in the current study, both groups achieved at least a 3-point reduction in pain and a 20-point increase in the VISA-A, yet no improvement in the PROMIS Physical Function. Even though patients with midportion AT are generally considered to have a higher rate of success and satisfaction with exercise than insertional AT,2,70 the current study did not detect any differences between AT types in improvement in pain, function, or global rating of change.

4.2.3. Efficacy of education and exercise on fear of movement

This is the first RCT to examine the impact of education and exercise on fear of movement and other pain-related psychosocial factors in tendinopathy.33 At 12-week follow-up, the PSE group had a decrease of 7.6 on the TSK-17, which exceeds the MCID of 5.5.34 Similarly, previous studies on PSE plus exercise for chronic neck or low back pain have reported a decrease of 5.4 to 12.6 points on the TSK by 12 weeks.19,30,32,42,45 By comparison, the PAE group had a decrease of 5.3 points, which is below the MCID and similar in magnitude to other exercise focused interventions, ranging from 1.2 to 4.0.19,30,32,42,45 Together these findings support that exercise interventions can affect psychosocial factors, yet the largest improvements may be achieved in combination with PSE. Additional research is needed to determine if PSE has other healthcare implications, such as the choice to pursue invasive treatments in the future or long-term engagement in physical activity.

4.3. Strengths and limitations

One strength of this study is the design of a placebo intervention that was likely to control for nonspecific aspects of the treatment, such as the quality of the materials, time with the clinician, and treatment provider. We included assessments to capture participation, treatment fidelity, and blinding,6,7 and the majority of participants in both groups believed that they were receiving the treatment that was more helpful for recovery (Table 6). Yet a limitation is that we did not capture treatment preferences of the physical therapist, and indicators of equipoise should be considered in the design of future clinical trials.17 While there are publicly available resources that could have increased fear of movement (eg, YouTube videos presenting Achilles tendon rupture information), we felt that it was unethical to provide participants with information that is not consistent with current state of evidence. By providing a neutral rather than a negative comparison intervention, we may have underestimated the potential difference between psychosocial and biomedical approaches to education that exist in real-world clinical settings. To assess this possibility, it would require a more pragmatic trial approach and a much larger sample size.43

A strength of the sample is that it represents a wide spectrum of patients, including both sexes and AT types as well as a wide range of ages and body mass index. To capture the typical care-seeking population, we excluded individuals with low (<3/10) and/or acute (<3 months) AT pain (Fig. 1). Given the importance of education during the initial onset of pain, it is unknown if education type would have been more influential on outcomes at an earlier stage of the diagnosis. Furthermore, the generalizability of these findings is limited to patients seeking noninvasive care, who may have less severely impaired physical function compared with patients seeking surgery. Our sample at baseline had a PROMIS Physical Function level that was nearly equivalent to the general population mean, resulting in a ceiling effect. In contrast, patients seeking surgery for AT often have a baseline level of function that is about 1 SD below the general population mean.2,26 While we detected a statistically significant improvement in function with noninvasive care, this did not reach the MCID for the PROMIS Physical Function. Future clinical trials on noninvasive treatments should consider using the VISA-A as a primary outcome, which is more responsive and is commonly used by other exercise studies for the AT population.21

4.4. Implications for future research

The interventions in the current study spent as much time on education as on exercise, both by the physical therapist during treatment visits and by the participant between visits. Overdosing time on education could be a waste of healthcare resources while spending an insufficient amount of time on education could fail to maximize the benefits of exercise. We found that a greater improvement in knowledge was associated with a greater improvement in pain, which supports the importance of integrating education with exercise to maximize clinical outcomes. Future work is needed to determine how to best match patient preferences and expectations with the educational approach and how to provide education both effectively and efficiently within clinical settings.

4.5. Clinical importance

These findings support clinicians to make a person-centered decision on which educational approach is best to combine with exercise for their patient. The current study findings are consistent with a pragmatic RCT by Traeger et al.67 in an acute low back pain population seeking standard of care treatments; there were no differences in pain reduction with the addition of 2 one-hour PSE sessions compared with a placebo-arm of active listening. Thus, an evidence-based approach to care would support selecting the type of education based on the patient preference and clinical experience over research evidence for a specific educational strategy.

5. Conclusions

Adding PSE to exercise for AT did not enhance improvements in pain and function when compared with adding a biomedically based education. Improvements in self-efficacy and knowledge gain were associated with a greater improvement in pain and function, indicating that acquiring skills for self-management of symptoms and the process of learning may be more important than the specific content of the educational approach. Patient education combined with exercise was effective at improving performance-based function and psychosocial factors but not CNS nociceptive processing in participants with AT.

Conflict of interest statement

R. L. Chimenti receives software from Siemens Medical Solutions USA, Inc. Professional and scientific societies have reimbursed her for time and travel costs related to presentation of research on pain and pain education at scientific conferences. G. L. Moseley receives royalties for key resources used for PSE (Explain Pain, Explain Pain Handbook: Protectometer, Explain Pain Supercharged, NOIgroup Publications, Adelaide, Australia), speaker fees for talks on contemporary pain science education, and consults to various organizations on pain science education and management. G. L. Moseley has also received support from Reality Health, ConnectHealth UK, Kaiser Permanente, AIA Australia, Workers' Compensation Boards and professional sporting organizations in Australia, Europe, South and North America. Professional and scientific bodies have reimbursed him for travel costs related to presentation of research on pain and pain education at scientific conferences/symposia. He has received speaker fees for lectures on pain and rehabilitation. M. Hall receives consulting fees from Tenex Health, royalties from UpToDate, Inc and holds stock in Sonex Health. C. de Cesar Netto is a paid consultant for Ossio, Stryker, and Medartis; a paid consultant and receives Stock Options to CurveBeam and Tayco Brace; a paid consultant/royalties from Paragon, Zimmer-Biomet, Nextremity, and Artelon; and is the Editor-in-Chief Foot and Ankle Clinics. K. A. Sluka serves as a consultant for Pfizer Consumer Health and Novartis Consumer Healthcare/GSK Consumer Health care and receives royalties from IASP Press. Other authors declare no conflicts of interest for this study.

Acknowledgements

Contributions to the study: The authors appreciate the guidance provided by our Data Safety Monitoring Board, which included Dr. Benjamin Miller (Independent Safety Officer), Dr. Carol Vance, Dr. Patrick Ten Eyck, Dr. Dana Dailey. The authors also appreciate the intellectual and artistic work that was generously contributed to the Pain Science Education handouts by Dr. Beverly Thorn with the Learning About Managing Pain (LAMP) Patient Workbook and Dr. Elan Schneider with retrainpain.org.

Funding for this study was provided by the National Institute of Arthritis Musculoskeletal and Skin Disease (NIAMS) research grant R00 AR071517 and by the Collaborative Research Grant from the International Association for the Study of Pain (IASP). Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Numbers UL1TR002537 and UL1TR002537. This research was funded in part by a Promotion of Doctoral Studies (PODS) The authors scholarship from the Foundation for Physical Therapy Research. These funding sources had no role in study design, collection, analysis/interpretation of data, or decision on submission for publication. G. L. Moseley was supported by a Leadership Investigator Grant from the National Health and Medical Research Council of Australia (ID 1178444). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other sponsors. Trial Registration: ClinicalTrials.gov NCT 04059146.

All authors made substantial contributions to the study design. R. L. Chimenti wrote the first draft of the manuscript with A. A. Post, K. A. Sluka, G. L. Moseley, E.K. Rio, M. Dao, H. Mosby, E. O. Bayman, M. Hall, C. de Cesar Netto, J. M. Wilken, and J. Danielson revising and approving the submitted version.

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Keywords:

Achilles tendon; Tendinopathy; Pain science education; Rehabilitation; Physical therapy; Tendon; Clinical trial; Biopsychosocial; Patient education; Disability; Exercise therapy; Chronic musculoskeletal pain

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