The Science of Pain: Dr. Yesh Navalgund Discusses How the Inspiring Discovery of the 2021 Nobel Prize in Medicine or Physiology Offers New Promise for Managing Pain

On October 4, the Nobel Assembly awarded the 2021 Nobel Prize in Physiology or Medicine jointly to Dr. David Julius and Dr. Ardem Patapoutian “for their discoveries of receptors for temperature and touch.” Their findings explain how heat, cold and touch initiate nerve impulses in the human nervous system. Affiliated board certified physician and director of physician education at the National Spine and Pain Centers, Dr. Yesh Navalgund, provides his insight into the potential impact that these significant discoveries will have upon those living with pain.

Contact National Spine & Pain Centers to schedule an appointment with an affiliated pain specialist today.

Discovering Receptors for Temperature and Touch

Dr. Julius, PhD, a professor of physiology at UCSF, examined how a component found in chili peppers named capsaicin activates a receptor in cells of sensory neurons. Capsaicin produces a burning sensation and behaves similarly to the feel of heat within the skin’s nerve endings. Through extensive genetic testing, Dr. Julius found that capsaicin activates a receptor named TRPV1.

Dr. Patapoutian, PhD, a molecular biologist and neuroscientist with Scripps Research in California, discovered pressure sensitive receptors named Piezo1 and Piezo2. These receptors are how the body perceive touch, blood flow and proprioception – the body’s ability to sense position and movement. Piezo1 and Piezo2 specifically regulate touch and stretching within the skin and internal organs, elucidating how breathing, blood vessels and bladder sensation function within the body.

These remarkable discoveries show how the Piezo receptors are responsible for pressure in a similar way that TRP receptors are responsible for the burning sensation and pain threshold. Of particular importance is that prior to this discovery, scientists did not know how a cell precisely recognized pressure or heat. Importantly, by determining how the signal of heat or touch is converted into electrical impulses and communicated to the brain, ongoing and future research can specifically focus on modulating receptors and controlling pain signals.

The Significance Pertaining to Pain Management

“This 2021 Nobel Prize discovery is critical in defining the actual field of interventional pain management” comments Dr. Navalgund. Indeed, it is not since the 1940’s when scientists realized how neurons work that such an extraordinary discovery has been made in the field of pain medicine. Often, patients do not perceive pain as a physiological process, which can limit seeking appropriate pain management care or even recognizing the possibility for proper pain management. With the discovery of various genes that trigger the reception of pain, it is appropriate and even logical for a person who feels pain to seek the specialized care of a pain management physician. Dr. Navalgund notes that “because pain specialists concentrate solely in the field of pain, they can utilize advances in pain management to provide a solution for the pain or direct the patient to the appropriate physician who will have a solution.” For example, a patient with back pain may seek an orthopedist consult, however, pain specialists are also highly qualified to examine and treat patients with back pain, particularly when this back pain originates from a source such as a pinched nerve. The pain specialist is uniquely trained to provide a comprehensive pain assessment as well as a thorough physical exam, and then employ the newest approaches in pain management to alleviate pain.

The work of Dr. Julius and Dr. Patapoutian has several notable implications for the future treatment of pain. Whereas traditional approaches to pain management often focused on medications, Dr. Navalgund points out that “now that we know which receptors are responsible for certain types of pain, we can tailor our care which can in turn lead to greater precision.” Utilizing the science from Dr. Julius’ and Dr. Patapoutian’s studies, researchers can determine the receptors responsible for specific types of pain which then allow for more precise pain symptom mitigation.

Patient Population Impacted

Those suffering with neuropathic pain, visceral pain, or inflammatory conditions can particularly benefit from Dr. Julius’ and Dr. Patapoutian’s work. Their discoveries will help to clarify how specific treatments work on various types of neuropathy, or nerve related pain, such as sciatica and CRPS (complex regional pain syndrome). Pain specialists are therefore able to be more selective with their treatments.

Visceral pain, or pain in the organs of the body, is commonly characterized as an elusive and difficult to treat pain. This pain may be present in the liver, stomach, or pancreas due to the presence of stretch receptors. Pain associated with pancreatitis, for example, is typically difficult to treat despite the use of various opioids. Opioids cannot cure pancreatic pain because they do not target the specific stretch receptors causing this pain. The discovery of the TRP and Piezo receptors provides greater insight into the specific type of visceral pain and offers future hope for better targeting this pain.

Inflammatory conditions causing pain, such as arthritis, are yet another area in which these discoveries may prove beneficial. In an inflammatory condition, pain management may occur through blocking each of the pain receptors, but without fully blocking each single receptor. This results in decreased pain sensation. Researchers can target this partial block to develop newer modes of pain relief and improve pain management associated with inflammatory conditions.

The discoveries from this year’s Nobel Prize in physiology or medicine may have additional implications in medical care. Lung conditions such as pneumonia can create difficulty with inhalation and exhalation both in terms of lung expansion and pain experienced while breathing. With the understanding of how the Piezo stretch receptors work, it is reasonable to focus research on therapy than can help patients with lung disease or pneumonia more efficiently expand their lungs and more comfortably take deeper breaths. The Nobel Prize discoveries also have the potential to help patients who may have suffered a spinal cord injury and have lost certain sensations such as detecting when their bladder is full. With the knowledge of receptors for pressure, scientists can determine which gene is responsible and not only find the deficits which cause the lack of sensation, but also replace them. “Anytime you find out why, it opens a new pandora’s box of research to finding solutions,” remarks Dr. Navalgund.

New Era of Technology

Though the discovery of the TRP and Piezo receptors is currently recognized with the 2021 Nobel Prize, the receptors were discovered more than two decades ago. The importance and enthusiasm for this breakthrough today lies in the combination of this scientific discovery, biopharmaceuticals, and technology. Technology allows for growth beyond drug manufacturing into technological advancements such as seen with devices. Spinal cord stimulators and peripheral nerve stimulators, for example, currently allow electrical waveforms to target regions of the body, but with the knowledge of TRP and Piezo, the hope is to affect only those receptors that targets very specific areas of the body. Dr. Navalgund comments, “knowing the mechanism of action in how these receptors work, I see a future in which device companies can start homing in on the receptors and locally use IC chips and electrical waveforms to manage pain.”

Technologies crucial to advancing this cause are largely a result of gene therapy, which allows for the splicing and replication of genes. Dr. Navalgund states, “the CRISPR* model, for example, allows researchers to apply the knowledge of the receptors discovered by Dr. Julius and Dr. Patapoutian to look for new ways to treat pain through gene editing.” Importantly, Dr. Julius and his lab were able to pinpoint the TRP receptors by deleting and adding genes to/from cells that did not respond to capsaicin until finding the genes that did react to the capsaicin in the hot pepper, thus determining which gene corresponded with TRPV1. Notably, despite the value of pinpointing the receptors that respond to certain types of pain, research is ongoing. Painful stimuli can after all serve an important purpose to prevent injury, so shutting down an entire receptor can be risky. The idea of gene editing is an integral part of research which can modulate receptors that are applicable to pain management. It is reasonable to expect that within this next decade, technology will be able to apply the information provided through these studies towards helping people with pain.

Pain Specialists at Forefront of Integrating Evidence-Based Practice and Technologies

Whether with minimally invasive spinal fusion or spinal cord stimulation devices, the track record of NSPC conveys a commitment to adopting the newest and safest treatments available to manage pain. The pain specialty has grown extensively through recent years to become less reliant on medications and instead integrate biotechnology, allowing pain experts to manage a presenting patient’s pain with greater precision. With the developments of Dr. Julius and Dr. Patapoutian’s studies, there is realistic hope for managing pain with even more precise science. Dr. Navalgund remarks that “pain management is an innovative specialty that is constantly examining and reexamining how to best manage painful conditions.” Pain specialists recognize that while collaborative care amongst various medical specialties can maximize patient well-being, pain specialists importantly provide a detailed and multifaceted approach to managing pain that is integral to patients suffering with various painful conditions. Pain physicians are uniquely trained and positioned within the clinical setting to utilize their medical education and expertise together with the most recent advances in science and technology to manage pain. NSPC is the leading institution in the nation to utilize the latest advances and technology with their patients. Dr. Navalgund points out that “while the ultimate goal is to cure pain, managing pain is sometimes a more realistic goal,” and pain specialists are compassionate and knowledgeable experts to help patients manage pain.

Further Reading

The Nobel Prize in Physiology or Medicine 2021 (The Nobel Prize Organization)

Nobel Prize Awarded for Research about Temperature and Touch (New York Times)

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