Nobel Prize Winners on Pain, Touch, and Proprioception

The 2021 Nobel Prize in Physiology or Medicine was awarded to David Julius and Ardem Patapoutian for their discoveries of how we detect touch and pain.

Somatosensation is how we register or perceive touch, warmth, pain, and other sensations in the brain. These sensations are important part of our life and the key to many manual therapies. However until recently it was unclear how the nervous system converted temperature and mechanical stimuli into electrical impulses.

In the late 1990s, David Julius from University of California tried to understand how the body responds to heat. Julius and his colleagues use capsaicin, the fiery ingredient in chili peppers. It is known that capsaicin, such as tiger balm, on contact with the skin activated pain receptors, but how it works was unclear. Julius and his team painstakingly tested in the lab using laboratory-grown neurons. By testing them one by one, they found  a gene in the sensory neurons that react to capsaicin. The gene makes cells to build a protein called TRPV1.

Patapoutian’s research pinpoints mechanosensitive cells, the ones that respond to pressure and touch. To identify the cells, Patapoutian and his team painstakingly poked the cells by pipette further examining the ones that responded. They then switched off individual genes one after the other until they found the gene responsible for perceiving touch. The gene also forms ion channels, in effect, tunnels in the cell walls that transmit nerve signals. They called it PIEZO1 after the Greek word for pressure. Further investigation, they found PIEZO2, another pressure-sensitive ion channel responsible for the perception of movement and body position in space or proprioception. Piezo proteins are mechanically activated ion channels. The PIEZO receptors regulate essential body functions, such as blood pressure, breathing, and control of the urinary bladder.

Sharkey makes the important point that “free mobile cells and epithelial cells, such as specialized cells in organs (PIEZO1, and 2), sense the tissue tension around them. Similar to chemical information via cytokines or ion concentrations, mechanical stimuli, as is provided in manual therapies, provides information translated via tension or compression and has a significant effect on local and global functions in the whole body based on these common sensory motifs involving the PIEZO family, central to this award-winning research”.

Relevance to Therapists

The two Nobel Laureates allowed us to understand how we can perceive pain, heat, cold and touch. This fundamental knowledge is crucial to understanding the origin of a wide range of syndromes, including chronic pain. For example, in the case of allodynia, where a person, post-injury, would perceive light touches as painful, could be related to the activation of PIEZO2 cells. The case of fibromyalgia, TRPV1 channel coul have a role in nociception and depressive-like behaviours.

Researchers have found that in some cases, people who are PIEZO2 deficient can exhibit

• Loss in proprioception, including loss of coordination, difficulty in walking, pseudoatheosis
• Loss touch perception, loss sensitivity to vibration
• Loss in pain sensation
• Difficulty breathing in infancy
• Diminisged perception of urinary urgency and urinary dysfunctions
• Hip dysplasia

Dr. Robert Schleip, a fascia researcher and therapist, provides an example of its relevance for manual and movement therapists. Patients with adolescent idiopathic scoliosis (AIS) often have a genetic variation that impacts the expression of the PIEZO2 receptor on their muscle spindles and Golgi tendon organs. They have impaired proprioception. This impaired proprioception is hardly noticeable when these patients perform movements with their eyes open, but they lose spatial coordination once they close their eyes. Schleip has been dealing with scoliotic patients for a long time and found this new insight very intriguing:

“It also brings up the question, whether a regular stimulation of paraspinal tissues with vibratory stimulation during infancy and early puberty in families with an increased presence of AIS could counteract the degree of AIS to some extent. And if so, whether standing on whole-body vibration platforms or daily dancing with open and closed eyes could be applied as effective modalities?”

Sharkey further points to the fact the activity of mechanosensitive ion channels, such as PIEZO1, requires low intensity, low amplitude force vectors demonstrating the therapeutic effects of gentle slow touch.

Regarding the TRPV receptors, Schleip pointed to the common application of topical pain relievers with capsaicin. The capsaicin molecules that migrate through the skin occupy TRPV receptors on some nociceptive neurons, preventing other nociceptive substances, such as substance-P, from stimulating these same nerve endings. Interestingly in many fibromyalgia patients, the skin flashing response to capsaicin cream treatment is much more enhanced and long-lasting than in normal patients.

Many therapists used instrument-assisted manual therapy techniques in recent years, such as with the Graston tools, Fasciq, or Gua Sha. They often applied these balms to enhance the tool application. Schelip says “Based on these new insights about the TRPV receptors, I have started to use capsaicin cream (usually with 2% concentration) more frequently combined with my Fasciq tool applications when aiming at a longer-lasting pain inhibition effect on the treated tissues.