Hyaluronic Acid Aggregation, Pain, and Manual Therapy

Introduction

For manual therapists, one major challenge is understanding the mechanisms that reduce pain for patients after soft tissue manipulation or mobilization.

There are many common reasons given for why it works, including:

• Counter-irritation of the nervous system
• Novelty of sensory input
• Breaking fibrotic adhesions, so tissues can slide
• Reflexive muscle relaxation through cutaneous nerve stimulation

Some of these are more justified than others, and their validity and practicality are debated all over the internet.

A paper was published in mid January 2020 in the International Journal of Environmental Research and Public Health. This post summarizes it and explains its significance, along with what it could mean for manual therapists.

02Pain without tissue damage

Sensations, pain or otherwise, come down to the firing of neurons to create action potentials, and then the cognitive processing of those signals, which leads to a subjective experience.

In an acute injury where there is tissue damage, pain is more than likely part of the body’s natural response to the injury. It gets us to protect that body part during the healing process.

However, pain does not necessarily imply tissue damage. There can be pain with no tissue damage.

That leads to speculation about what causes the pain. Is it a central processing error? Is it due to peripheral sensitization?

Depending on a variety of factors, a free nerve ending could need less stimulation to fire an action potential, resulting in a painful experience with no tissue damage.

The article under examination leads to a hypothesis: aggregated hyaluronic acid (HA) in the extracellular matrix (ECM) of the deep fascia, which is densely populated with nerve endings, may be lowering the stimulation needed to fire off those nerve endings, leading to pain.

Understanding why this may be the case takes some review of concepts, and an examination of what was performed in the study. Let’s take a look.

03Glycosaminoglycans and water

Glycosaminoglycans, or GAGs, are a class of molecules in the body that are essentially strings of double sugars (disaccharides). They have a strong polarity, which leads them to bond with water molecules.

Hyaluronic acid (HA) is one category of GAGs. It makes up the ground substance of the extracellular matrix (ECM) in connective tissue, nerve tissue and epithelial tissue.

In the ECM, there is bound and unbound water:

Bound water

Water in the ground substance that is bound to GAGs, since they are strongly polar.

Unbound water

Water in the ground substance that is not bound to GAGs.

Presumably, the more bound water there is, the more squishy and slippery the ground substance is. The more unbound water there is, the more viscous and less slippery it is.

This study suggests that HA not bound with water can self-aggregate, sticking together and increasing the viscosity of the tissue. That leads to what the study looked at:

04T1ρ MR, DASH index and Fascial Manipulation®

The study had 5 participants with elbow pain not due to tissue damage or underlying disease.

To begin, they performed a type of magnetic resonance (MR) study called T1ρ, which can measure bound and unbound water. They also gave the participants a DASH questionnaire (Disabilities of the Arm, Shoulder and Hand).

Over the next 3 weeks, therapists performed one 40-minute session of Fascial Manipulation® per week, using that specific technique system.

After the treatment sessions were finished, they followed up with another MR and another DASH.

The results demonstrated a correlation between the DASH score and the bound and unbound water.

When there was more unbound water, there was a higher DASH score. When there was more bound water, there was a lower DASH score.

After the treatments, there was more bound water and a lower DASH score. That suggests the manual therapy decreased pain and improved function, while also shifting the water from unbound to bound.

There is no causation implied here, but there is correlation.

05Speculation and conclusion

1. Perhaps certain types of manual therapy can agitate the aggregated HA, allowing its polar ends to attract water. That would be why unbound water decreased and bound water increased.
2. Perhaps aggregated HA, since it can’t bind to water, creates a subtle shift in the charge around the nerve ending, so the nerve needs less stimulation to fire an action potential. This could potentially explain the improved DASH scores.
3. Perhaps the dissolution of aggregated HA, and the drop in viscosity that follows, is part of why a person feels “looser” after manual therapy.
4. Perhaps this is why the manual therapist may feel the tissue as less stiff after treatment.

Above all, perhaps it is just part of the equation. The human body is a system of systems, not so simple as one cause and one effect.