🧠 When the Brain Can’t Clean Itself: How Glymphatic System Dysfunction Affects Pain, Fog, and Recovery

A Physiotherapist’s Perspective on Medications, Pain, and the Glymphatic System

By Greg Dea | Clinical Sports Physiotherapist | Educator in Functional Fluid Flow

The Brain Has a Plumbing System—And It Matters for Physio

Many of our clients present with pain, impaired mobility, poor motor control, and sometimes a foggy mind or unexplained fatigue. We assess their movement, provide manual therapy, guide their training—and sometimes scratch our heads wondering why change is so slow.

But what if the issue isn’t just mechanical or muscular?

What if the problem lies deeper—in the brain's ability to clear waste?

Enter the glymphatic system, the brain’s fluid clearance pathway, and a less obvious but crucial piece of the recovery puzzle.

What Is the Glymphatic System?

Think of it as the brain’s overnight cleaning crew. While we sleep, cerebrospinal fluid (CSF) washes through the brain tissue, removing metabolic waste like amyloid beta, tau proteins, and inflammatory byproducts. This process is largely powered by aquaporin-4 (AQP4) water channels located on astrocytes—the brain’s helper cells.

In short:

No AQP4 function = No brain drainage = Cognitive sludge + inflammation + pain sensitisation

Figure: Anatomical routes of brain fluid drainage, highlighting the role of astrocytic AQP4 water channels in glymphatic transport. Impairments in this system are increasingly linked to neuroinflammation, poor clearance of neurotoxins, and reduced motor control.  (Adapted from Sun et al., 2018: Progress in Neurobiology)

The Silent Saboteurs: Medications That Impair Glymphatic Flow

Here’s where things get clinically interesting.

Many of our patients are prescribed antidepressants, antipsychotics, or anxiolytics—understandably so, given the mental health burden of chronic pain. But what’s rarely discussed is that some of these medications may impair AQP4 function or localization, and thus reduce glymphatic clearance.

Drugs with known or suspected AQP4-modulating effects:

• Amitriptyline (tricyclic antidepressant): Downregulates AQP4 in preclinical studies

• Fluoxetine (SSRI): May reduce AQP4 expression, affecting fluid transport

• Haloperidol, Clozapine (antipsychotics): Influence astrocyte behaviour and glial inflammation

• Valproate, Benzodiazepines: Alter glial excitability and potentially astrocytic swelling

🧠 The problem? Many of these medications either reduce AQP4 or mislocalise it away from its key role near blood vessels—thus disturbing glymphatic flow.

Why Physiotherapists Should Care

Neuroinflammation, glymphatic dysfunction, and pain are tightly interwoven.

• Neuroinflammation increases central sensitisation—patients feel more pain from less input.

• Swollen astrocytes and poor fluid drainage impair synaptic transmission and neuroplasticity.

• Reduced clearance of inflammatory molecules creates a sustained brain threat response—disrupting motor control, coordination, and learning.

So when we see:

• Unexplained or persistent pain

• Poor recovery from treatment

• Motor control issues that "don’t make sense"

• Brain fog or mental fatigue

We should consider: Is the brain backed up?

The Clinician’s Conundrum

Of course, these medications are often essential for mental health. But it's possible that:

• A client’s pain is both psychological and physiological

• Their medication is helping in one area while quietly hindering another

• We're chasing peripheral solutions to what is, in part, a central fluid clearance issue

What Can We Do About It?

1. Understand the medications our clients are on, and how they may affect brain physiology.

2. Screen for glymphatic symptoms: sleep disruption, brain fog, heavy head, poor balance.

3. Encourage deep sleep hygiene, especially slow-wave sleep, which drives glymphatic clearance.

4. Use parasympathetic-enhancing strategies: manual therapy, breathwork, vagal nerve stimulation, Access Bars, etc.

5. Refer or co-manage with GPs/psychiatrists to gently open discussion about medication side effects if recovery is plateaued.

Final Thoughts

In Functional Fluid Flow, we talk about tissue, pressure, and behaviour. But behaviour isn’t just muscular—it’s also neurological. If the brain can’t drain, it can’t learn, adapt, or regulate pain effectively.

It’s time we give our clients the gift of clean neurology.

Because sometimes the best treatment isn’t another exercise—it’s a restful night, a quieter astrocyte, and a better flow upstairs.