Could a “waste management problem” be involved in chronic pain?   July 10th, 2022

Could a “waste management problem” be involved in chronic pain?

Distinguishing normal from abnormal when interpreting brain scans can be challenging, especially as a novice. One of the patterns you might notice is that certain brains have enlarged perivascular spaces. These spaces, also referred to as “Virchow-Robin” spaces, are generally considered normal.

However, as with many things in science, insights evolve. The recent discovery of the glial-lymphatic system, or the so-called “glymphatic system” in the brain, has attracted renewed attention to these perivascular spaces. They are believed to form an essential network that promotes the movement of cerebrospinal fluid (CSF) into the brain, to clear out metabolic waste – a process that appears to be closely regulated by sleep and norepinephrine.

When these perivascular spaces are enlarged, it could be the manifestation of some “blockage” caused by an accumulation of waste products. On the other hand, the enlargement may also be an adaptive response of the glymphatic system to clear the debris. We don’t understand it fully yet.

There is, however, increasing evidence (mostly from rodent models and post-mortem studies) that a faulty clearance by the glymphatic system is implicated in a multitude of neurodegenerative disorders.

It seems that this system also dysfunctions in (chronic) pain, where poor sleep and dysregulation of norepinephrine are common. Interestingly, novel non-invasive magnetic resonance imaging (MRI) techniques can now visualize the glymphatic system in alive patients.

Hopefully, this will lead to discoveries and treatments that can improve the brain’s “waste management system” in many of these patients. I’d say fascinating times ahead!

Thijs Vande Vyvere, Ph.D.

Postdoctoral Research Fellow, University of Antwerp & Antwerp University Hospital.

2022 Pain in Motion

References and further reading:

Troili F., Cipollini V., Moci M., Morena E., et al. Perivascular Unit: This Must Be the Place. The Anatomical Crossroad Between the Immune, Vascular and Nervous System. Front Neuranat (2020).

Albayram, M.S., Smith, G., Tufan, F. et al. Non-invasive MR imaging of human brain lymphatic networks with connections to cervical lymph nodes. Nat Commun 13, 203 (2022).

Wang A., Chen L., Tian C., Yin X. et al. Evaluation of the Glymphatic System with Diffusion Tensor Imaging-Along the Perivascular Space in Cancer Pain. Front Neurosci (2022).