Background & Aims
Rotator cuff tendinopathy (RCtend) is the most common shoulder diagnosis. Unfortunately, outcomes for RCtend are variable, with 40-50% developing recurrent or chronic pain. Mechanistic models of RCtend implicate tendon structural deficits as the primary source of nociception, but tendon structure poorly explains pain, disability, and variance in clinical outcomes. Brain-related deficits in pain and sensorimotor processing relate to symptom severity and chronic pain, but current measures are only indirect estimations. Concurrent direct measures of tendon structure and intrinsic brain activity are needed to identify the peripheral and central contributions to symptom severity and clinical outcomes.
Aim 1: Define central (brain) biomarkers for rotator cuff tendinopathy controlled for the effect of tendon structure.
Aim 2: Determine the relative contributions of tendon structure and intrinsic brain activity associated with pain, disability, and clinical outcomes after 8 weeks of exercise
Methods
13 individuals with right-sided RCtend and 13 healthy controls (HC) matched for age, sex, body mass index, and handedness were recruited for participation. Tendon structure was measured with ultrasound with longitudinal tendon thickness as the primary outcome measure. Resting-state brain activity was measured with functional magnetic resonance imaging. Functional connectivity matrices were created with the Schaefer functional connectivity atlas with 400 parcels and 7 networks. Patients underwent a standardized, resistance exercise protocol for 8-weeks, with tendon and brain imaging measurements at baseline, 4-weeks, and 8-weeks. HC were collected at baseline for cross-sectional comparison. Participants completed the PENN Shoulder Score at each time point to measure pain, function, and satisfaction. Recovery was defined with responding ‘yes’ on the Patient Acceptable Symptom State at 8-weeks.
Results
RCtend had thicker tendons (mean difference= 0.9mm (95%CI:0.4, 1.5), p=0.003).
Aim 1: A hub in the fusiform cortex in the dorsal attention network was increasingly connected to 4 nodes within the sensorimotor network (mean difference= 0.8 [95% CI:0.2 1.3]; p=0.009). These nodes span the shoulder sensorimotor areas.
Aim 2: Tendon thickness positively relates to pain (r= 0.35, p=0.25) but had a stronger relationship to function (r= -0.49, p=0.1). Functional connectivity between the shoulder sensorimotor node and the dorsal attention network node was positively related to function (r=0.56, p=0.04) and negatively related to pain (r=-0.48, p=0.1) in those with RCtend. There was increased tendon thickness at baseline in responders (mean: 5.0mm ±0.5) compared to nonresponders (mean: 4.0mm ±0.5), and no difference between nonresponders and controls (mean: 3.9mm ±0.5). Nonresponders (mean: 0.9 ±0.2) had increased functional connectivity compared to responders (mean: 0.25 ±0.5).
Conclusions
In agreement with prior literature, increased tendon thickness is a biomarker for RCtend and has a weak, positive relationship to pain and a moderate negative relationship to function. After controlling for the differences in tendon thickness, increased resting-state functional connectivity between the dorsal attention network and shoulder-specific sensorimotor areas was found in those with RCtend. Functional connectivity had a moderate, negative relationship to function and a moderate, positive relationship to pain. These results are in agreement with the known descending pain modulation effect of this functional connectivity pair. In other words, increased connectivity serves to inhibit the sensation of pain thereby improving function. Increased functional connectivity at baseline and no increase in tendon thickness compared to controls defined those who responded poorly to an 8-week resistance exercise protocol.
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