Neural Mechanisms of Muscle Control in Individuals With Knee Pain

Rationale: Two prior randomized controlled trials (RCT) have highlighted the importance of
hip muscle activation and strengthening as a treatment strategy for patellofemoral pain
(Khayambashi, 2014; Khayambashi, 2012). Here, we propose a pilot study to acquire preliminary
data to power a larger study to reveal the neural mechanism underlying the effectiveness of
this intervention to promote its evidence-based incorporation into clinical practice.

Intervention: 4 weeks of quadriceps muscle versus 4 weeks of hip strengthening exercises.

Purpose: To determine changes in brain functional connectivity related to pain reduction
induced by the strengthening exercises.

Study population: Males and females with a history of unilateral knee pain.

Methodology: Functional magnetic resonance imaging (fMRI) will be used to quantify functional
connectivity of brain regions related to hip muscle activation. Functional connectivity will
be quantified before (pre) and after (post) 4 weeks of quadricep or hip muscle strengthening
exercises.

Arms: As above, there are 2 arms. 4 weeks of quadriceps strengthening exercises (Arm 1)
versus 4 weeks of hip strengthening exercises (Arm 2).

Outcomes: At the pre and post-intervention sessions in each participant, we will quantify the
brain functional connectivity between hip muscle motor cortex and the 1) thalamus, 2) basal
ganglia, and 3) insula, and 4) the periaqueductal gray. We will also quantify self-report of
pain and biomechanical function of the knee and hip.

Follow-up: A six month follow-up is planned for this pilot study.

Analysis Plan and Statistics: Functional connectivity of hip muscle motor cortex will be
extracted using standard statistical software for brain mapping. A repeated measures ANOVA
will be used to assess change in functional connectivity in the hip and knee group. Pain
decreases in the both groups will be quantified and reported.

Inclusion Criteria:

1. Pain located specifically around the patellofemoral articulation (vague or localized).

2. Readily reproducible pain (3 out of 10 on a visual analog scale) with at least 2 of
the following functional activities commonly associated with PFP: stair ascent or
descent, squatting, kneeling, prolonged sitting, or isometric quadriceps contraction.

3. Reports of pain greater than 3 months duration.

Exclusion Criteria:

1. Previous history of knee surgery.

2. History of traumatic patellar dislocation.

3. Neurological involvement that would influence gait.

4. Contraindications to MR imaging: implanted electronic devices (i.e. pacemaker), or
metallic implants (i.e. aneurysm clips, fixation screws).