CNS Modulation Accompanying Patellar Tendinopathy: A 2-Part Review of Central Mechanisms & Neuroplastic Training

By Dr. Shanon M. Fronek, PT, DPT, SCS, CSCS, Dip. Osteopractic

Part 1: CNS Modulation Accompanying Patellar Tendinopathy: A Review of Central Mechanisms?

Human movement is influenced by the integrity of a complex multi-level hierarchical control system. This system includes peripheral components, such as muscle and tendon, which influence and are regulated by the central nervous system (CNS) via motor and sensory connections. The primary regions of the CNS involved in motor control are the primary motor cortex and corticospinal tract.(1)?Corticospinal control of the muscle refers to motor unit activation via excitatory and inhibitory inputs from the CNS onto the spinal motorneuron pool, which ultimately affect tendon loading and motor performance.(2)??Conceivably, a mechanical lesion in a tendon caused by pathology elicits a series of multi-level adaptations, both centrally within the excitatory and inhibitory neural pathways, and peripherally within the local muscle-tendon unit.?

Several musculoskeletal conditions have shown to result in persistent changes in motor control of the involved area and alterations in the primary motor cortex.(3)?Individuals with patellar tendinopathy (pathologically observed on ultrasound) demonstrated landing patterns different from controls and less variability in movement.(2,4)?Similarly, a protective back strategy has been observed in asymptomatic controls with an expectation of back pain and those with recurrent back pain even when they were pain free.(2,5,6)?While it is debatable whether movement invariability serves as a protective mechanism or adaptation to maintain performance, these changes in motor control persist in the absence of pain and imply non-resolution of altered hierarchical control. Failure to reinstate normal movement variability has been proposed as a possible risk for recurrence.(2)

The high incidence of bilateral presentation with predominantly unilateral load suggests potential for interhemispheric competition modulating corticospinal motor control in the involved and uninvolved extremity.(2) The high recurrence rate and bilateral presentation suggests current rehabilitation strategies fail to?restore corticospinal control?of the muscle-tendon unit. An understanding of the current evidence regarding CNS modulation accompanying patellar tendinopathy may help to maximize the opportunity for neuroplasticity and encourage a multi-level rehabilitative approach.??

Changes in motor output are a combination of changes in the excitatory and inhibitory neural pathways. Transcranial magnetic stimulation (TMS) is temporal measurement of cortical plasticity by inferring excitation and inhibition of?the spinal and supraspinal pathways.?TMS measures are taken in the contralateral hemisphere to the involved extremity.?Single-pulse TMS is used to obtain measures that are reflective of net excitatory drive to the muscle via the corticospinal pathway.(7) The amplitude of motor-evoked potential (MEP) or slope of the stimulus-response (SR) curve represent corticospinal excitability (CSE).(3)?The slope of the SR curve reflects the physiological strength of corticospinal projections onto the motorneuron pool, membrane excitability and corticospinal cell recruitment. Inhibitory mechanisms also influence the slope of the SR curve because of synaptic inputs altering descending drive to the muscle.?Short-interval intracortical inhibition (SICI), a measure of paired-pulse TMS, is thought to be mediated at a cortical (supraspinal) level rather than at the spinal cord. SICI is represented as a percentage ratio that quantifies the effect of inhibitory interneurons that synapse onto pyramidal cells in the primary motor cortex.?A lower SICI indicates a relatively higher level of inhibition.(8)

TMS studies have shown?jumping athletes with patellar tendinopathy (PT) demonstrate greater corticospinal excitability and?markedly increased cortical inhibition on the affected extremity?compared to activity-matched controls.(2,3,8)?Rio et al (2015) measured?CSE using single-pulse TMS in twenty-nine jumping athletes; eleven with bilateral or unilateral PT, ten with anterior knee pain (AKP), and eight controls. The group with PT was observed to have a significantly steeper slope of the stimulus-response (SR) curve, indicating higher corticospinal excitability and altered ability to modulate corticospinal control of the rectus femoris in the affected extremity.(8)?A separate publication by Rio et al (2015) examined measures of CSE?and SICI in six jumping athletes with confirmed diagnosis of bilateral or unilateral PT. High levels of intracortical inhibition were present at baseline in all PT subjects with a mean SICI ratio of 27% on the affected side. For comparison, data reported for the quadriceps in normal participants ranges between 50% and 70%.(3)?Similarly, unpublished data cited by?Rio et al (2016)?found markedly increased cortical inhibition on the affected extremity with a SICI ratio of 17.12% (n=4) compared to control with a SICI ratio of 58.78% (n=6).(2)?These findings highlight an impaired ability of the CNS to balance inhibitory and excitatory mechanisms, which may result in overshooting or undershooting recruitment of the affected extremity during functional?tasks.(8)

Unpublished data cited by Rio et al (2016) investigated abnormalities in excitatory and inhibitory corticospinal mechanisms in the affected and unaffected extremity in individuals with unilateral PT compared to activity-matched controls. The affected lower extremity demonstrated corticospinal hyperexcitability, and markedly increased cortical inhibition (SICI ratio of 17.12%). The contralateral pathway controlling the unaffected side appeared less excitable than both the affected side and controls, and displayed increased cortical inhibition (SICI ratio of 19.13%).(2)?These preliminary findings replicate the?adaptive response of greater interhemispheric inhibition and bilateral extremity changes?seen following a unilateral stroke that affects the primary motor cortex.(2,9)?The clinical implications of these findings suggest a danger in using the unaffected limb as a control in studies investigating CNS modulation in individuals with PT. More importantly, it highlights the need for further evaluation of techniques that modulate excess inhibition given strength training the affected limb may further drive inhibition to the unaffected limb.?

Part 2: Maximizing Training Induced Neuroplastic Gains

The central nervous system (CNS) provides synaptic input to the spinal motorneuron pool, driving motor unit recruitment and magnitude of muscle activation, and therefore force production through the muscle-tendon unit. Studies utilizing transcranial magnetic stimulation (TMS) measures?have shown imbalances between the excitatory and inhibitory influences over muscle activation around the patellar tendon in the involved and uninvolved extremity. Interhemispheric connections and corticospinal pathways are potential avenues for these bilateral changes to occur. Additionally,?individuals with patellar tendinopathy (PT) have demonstrated landing patterns different from controls and less variability in movement.(1)?Neural control adaptations of the quadriceps muscle leading to aberrant tendon load may contribute to the development of bilateral pathology and/or recalcitrance and recurrence of PT.(2)?An understanding of cortical plasticity in response to motor training in individuals with and without PT may facilitate improvements in at least one aspect of the multimodal treatment plan.?

Rapid development of muscle strength in the absence of muscle hypertrophy occurs as result of changes in the CNS. Training induced adaptations thought to account for changes in muscle strength include reduced co-activation of antagonist muscles, increased activation of agonist muscles, and increased motorneuron excitability.(3,4)?Further support for the complexities of neural adaptation following a period of strength training is the phenomenon of cross-education.(5)?Originally defined by?Scripture et al (1894)?as the improvement in motor performance of an untrained limb following unilateral motor training in the opposite limb,(6)?pooled data have reported a mean 7.6% increase in strength in the untrained limb, corresponding to 52% of the strength gained in the trained limb.(3,7)?Unfortunately, neural mechanisms mediating cross-education remain elusive despite several reports in the literature. A review conducted?by Frazer et al (2018) indicate?that neural adaptations to cross-education of muscle strength likely represents a continuum of change within the CNS that involves structural and functional changes within cortical motor and non-motor regions and subtle changes along the entire neuroaxis. These changes include increased corticospinal excitability, reduced cortical inhibition, reduced interhemispheric inhibition, changes in voluntary activation and new regions of cortical activation.(5)?While developing a better understanding of the mechanisms mediating cross-education in strength training is a fundamental first step to improve clinical practice, it is important to consider other variables that may influence neural adaptations in the presence of pathology.

Externally paced training using visual or auditory cues, such as a metronome, to match the pace of the prescribed contraction phases may be a key component of CNS modulation.?Traditional self-paced training describes a process without externally structured timing cues (metronome) or advice about timing of the eccentric and concentric phases.(2)?In comparison to self-paced training, externally paced training has been found to induce significant improvements in ipsilateral and contralateral adaptations in excitatory and inhibitory neural pathways in healthy participants.(2,3,8)

Motor skill training, such as visuomotor tracking, and strength training are two types of training modalities that may influence cortical?plasticity. Leung et al (2017) examined?corticospinal responses following skill training (task synchronized to visual cue), metronome-paced strength training (task synchronized to audible cue), and self-paced strength training (no visual or auditory synchronization). The main findings of this study were that four weeks of visuomotor skill training and metronome-paced strength training resulted in an increase in corticospinal excitability (CSE) and a decrease in short-interval intracortical inhibition (SICI). Interestingly, self-paced strength training had no effect on CSE or SICI. This result has important clinical implications as corticospinal responses to cross-education are dependent on the type of motor training via auditory or visual cues.(9)

Tendon neuroplastic training (TNT) is a protocol developed by?Rio et al to?apply the concept of externally paced quadricep strength training in individuals with PT. The protocol includes an isotonic group and an isometric group. Groups are matched for time under load and rest between sets.(10)?All participants listened to an audio recording for task synchronization. Rio et al (2015) investigated the immediate effects of isometric and isotonic exercise on pain?and cortical function in six jumping athletes with bilateral or unilateral PT. A single session of isometric exercise resulted in an immediate significant improvement in tendon pain on the single limb decline squat (SLDS), maximal voluntary isometric contraction (MVIC) torque for the quadriceps, and reduced intracortical inhibition (SICI) of the involved extremity compared to baseline measures. Improvements in pain and MVIC torque observed in the isometric group were sustained for at least 45 minutes following the intervention.?No between group differences were observed in measures of corticospinal excitability.(10)?Rio et al (2017) investigated the cumulative effect of strength training during a 4-week competitive season on pain and function in twenty jumping athletes with unilateral and bilateral PT. The isometric group was observed to have greater single session improvements in tendon pain during the SLDS compared to the isotonic group.(11)?Unpublished data cited by Rio et al 2016 reports a subgroup of nine athletes from the Rio et al (2017) trial?completed corticospinal testing. Changes in CSE were observed over four weeks with week four most closely representing normal CSE in jumping athletes without PT.(2)?While unable to determine differences between groups due to the small sample, all athletes improved to be within the normal range of cortical inhibition of the quadriceps following the intervention (normal ranges between 50% and70%.)(10)?These findings are in line with a similar study investigating the influence of a 4-week in-season exercise program on tendon pain and function in jumping athletes?with PT.(13)?This?study found both?isotonic and isometric exercise have similar results in improving tendon pain on the SLDS and function in athletes with PT over 4 weeks.?There were no significant between group differences.?

Unimodal rehabilitative programs aimed solely at peripheral tissue are unlikely to address all components associated with the multi-level hierarchical control system responsible for human movement.(2)?Addressing neuromechanical maladaptations as result of a mechanical lesion early and throughout the rehabilitative process may be the missing link to reinstating movement variability, lowering risk for injury recurrence, enhancing neuromotor recruitment and muscle hypertrophy, and potentially optimizing the return to sport timeline.?Collectively these findings suggest that externally paced isometric exercise performed at MVIC > 70% may be superior to isotonics for immediate and short-term pain relief, as well as for modulating high levels of cortical inhibition.?Preliminary findings from the aforementioned studies suggest CSE may require a time-dependent component of exposure to neuromotor interventions before values are within normal activity-related range. Importantly, these changes occurred without evidence of decline in motor performance (fatigue) and athletes did not miss any training?sessions because of tendon pain. The clinical implication is that quadricep isometrics may be used prior to activity and in early stages of rehab to modulate patellar tendon pain without inducing fatigue or limiting participation. Improvements in pain and MVIC may be sustained for up to 45 minutes post intervention.?

Neuroplastic training in the early rehabilitative phases may incorporate?visuomotor skill training and/or metronome-paced isometric strength training. Certain clinical scenarios may impede or prevent loading of the local muscle-tendon unit (e.g., high irritability, injury severity, post surgical).?In these instances, dry needling may be considered as an alternative mode of tendon neuroplastic training. Preliminary evidence exists to suggest dry needling may be an adjunctive modality in tendon rehab. Following one 30-minute session of dry needling, healthy controls showed significant changes in corticospinal excitability and a decline in interhemispheric inhibition from the contralateral motor cortex.(14)?Whether these changes will be observed in the same way in individuals with PT needs to be answered by following studies.?

Finally, while outside the scope of this review, it is important to note that isometric exercise is only a small component of the treatment plan. Tendon loading must be progressed beyond isometrics to enable a resilient tendon to return to sport. Readers are encouraged to refer the following articles for strategies related to tendon loading progressions.(15-17)

References

(Part 1)

1. Chang YJ Kulig K.?The neuromechanical adaptations to Achilles tendinosis.?J Physiol.?2015;593(15):3373-3387.
2. Rio E, Kidgell D, Moseley GL, Gaida J, Docking S, Purdam C, Cook J. Tendon neuroplastic training: Changing the way we think about tendon rehabilitation: A narrative review.?Br J Sports Med.?2016;50:209–215.?
3. Rio E, Kidgell D, Moseley GL, Cook J.?Elevated corticospinal excitability in patellar tendinopathy compared with other anterior knee pain or no pain.?Scand J Med Sci Sports.?2016;26:1072–9.?
4. Edwards S, Steele JR, McGhee DE, Beattie S, Purdam C, Cook JL. Landing strategies of athletes with an asymptomatic patellar tendon abnormality.?Med Sci Sports Exerc.?2010;42:2072–80.?
5. Moseley GL, Nicholas MK, Hodges PW. Does anticipation of back pain predispose to back trouble??Brain. 2004;127(Pt 10):2339–47.?
6. Hodges PW, Richardson CA. Inefficient muscular stabilization of the lumbar spine associated with low back pain. A motor control evaluation of transversus abdominis.?Spine. 1996;21(22):2640-50.
7. Latella C, Kidgell DJ, Pearce AJ. Reduction in corticospinal inhibition in the trained limb following unilateral leg strength training.?Eur K Appl Physiol. 2012;112:3097-3107.
8. Rio E, Kidgell D, Purdam C, Gaida J, Moseley GL, Pearce AJ, Cook J. Isometric exercise induces analgesia and reduces inhibition in patellar tendinopathy.?Br J Sports Med.?2015;49:1277–1283.?
9. Butefisch CM, Wessling M, Netz J, Seitz RJ, Homberg V. Relationship between interhemispheric inhibition and motor cortex excitability in subacute stroke patients.?Neurorehabil Neural Repair. 2008;22:4–21.

(Part 2)

1. Edwards S, Steele JR, McGhee DE, Beattie S, Purdam C, Cook JL. Landing strategies of athletes with an asymptomatic patellar tendon abnormality.?Med Sci Sports Exerc.?2010;42:2072–80.?
2. Rio E, Kidgell D, Moseley GL, Gaida J, Docking S, Purdam C, Cook J. Tendon neuroplastic training: Changing the way we think about tendon rehabilitation: A narrative review.?Br J Sports Med.?2016;50:209–215.?
3. Latella C, Kidgell DJ, Pearce AJ. Reduction in corticospinal inhibition in the trained and untrained limb following unilateral leg strength training.?Eur J Appl Physiol. 2012;112:3097-107.
4. Mason J, Frazer AK, Avela J, Pearce AJ, Howatson G, Kidgell DJ. Tracking the corticospinal responses to strength training.?Eur J Appl Physiol. 2020;120(4):783-798.
5. Frazer AK, Pearce AJ, Howatson G, Thomas K, Goodall S, Kidgell DJ. Determining the potential sites of neural adaptation to cross-education: implications for the cross-education of muscle strength.?Eur J Appl Physiol. 2018;118(9):1751-1772.
6. Scripture E, Smith T, Brown E. On the education of muscular control and power.?Stud Yale Psychol Lab. 1894;2:114–119.
7. Carroll TJ, Herbert RD, Munn J, Lee M, Gandevia SC. Contralateral effects of unilateral strength training: evidence and possible mechanisms.?J Appl Physiol. 2006;101:1514–1522.
8. Kidgell DJ, Stokes MA, Pearce AJ. Strength training of one limb increases corticomotor excitability projecting to the contralateral homologous limb.?Motor Control. 2011;15:247–66.?
9. Leung M, Rantalainen T, Teo WP, Kidgell DJ. The corticospinal responses of metronome-paced, but not self-paced strength training are similar to motor skill training.?Eur J Appl Physiol. 2017;117:2479–2492.
10. Rio E, Kidgell D, Purdam C, Gaida J, Moseley GL, Pearce AJ, Cook J. Isometric exercise induces analgesia and reduces inhibition in patellar tendinopathy.?Br J Sports Med.?2015;49:1277–1283.
11. Rio E, van Ark M, Docking S, Moseley L, Kidgell D, Gaida JE, van den Akker-Scheek I, Zwerver J, Cook J. Isometric contraction are more analgesic than isotonic contractions for patellar tendon pain: An in-season randomized clinical trial.?Clin J Sport Med. 2017;27(3):253-259.
12. Rio E, Kidgell D, Moseley GL, Cook J.?Elevated corticospinal excitability in patellar tendinopathy compared with other anterior knee pain or no pain.?Scand J Med Sci Sports.?2016;26:1072–9.?
13. van Ark M, Cook JL, Docking DI, Zwerver J, Gaida JE, van den Akker-Scheek I, Rio E. Do isometric and isotonic exercise programs reduce pain in athletes with patellar tendinopathy in-season? A randomized clinical trial.?J Sci Med Sport. 2015;19(9):702-6.
14. Yang Y, Eisner I, Chen S, Wang S, Zhang F, Wang L. Neuroplasticity changes on human motor cortex induced by acupuncture therapy: A preliminary study.?Neural Plast. 2017;4716792.
15. Cook JL and Purdam CR. The challenge of managing tendinopathy in competing athletes.?Br J Sports Med. 2013;0:1-6.?
16. Cook J, Stasinopoulos D, Bismee J-M. Insertional and mid-substance Achilles tendinopathies: eccentric training is not for everyone-updated evidence of non-surgical management.?J Man Manip Ther. 2018;26(3):119-122.?
17. Malliaras P, Cook J, Purdam C, Rio E. Patellar tendinopathy: clinical diagnosis, load management, and advice for challenging case presentations.?J Orthop Sports Phys Ther.?2015;45(11):887-898.?