Research into brain mechanisms is resulting in new options for patients
An estimated 20.4 percent, or 50 million, Americans live with chronic pain, leading to nearly $560 billion each year in direct medical costs, lowering productivity and increasing disability. Today, chronic pain is one of the most common reasons for adults to seek medical care and has led to opioid dependence, anxiety, depression, restrictions in mobility and daily activities and overall reduction in quality of life. While short-term pain-relieving therapies provide relatively good solutions, an effective long-term solution for chronic pain has yet to be identified.
To establish what we are missing in chronic pain treatment, we first need to understand how the body perceives and responds to pain. Throughout the body we have pain-receptive neurons, known as nociceptors, which respond to damaging or potentially damaging stimuli by sending a “possible threat” signal. The signal travels through the nerves to the spinal cord, which processes the pain message and carries it up to the brain, where it is further processed by the thalamus and then sent to the cerebral cortex, where we perceive it.
Upon receiving a nociceptive pain message, the brain’s pain regulation network can either inhibit or enhance the pain experience according to the context. Typically, an acute pain message is often considered a “good” signal since it alerts the body to potential damage, allowing protective action that can thereafter be inhibited. Chronic pain, however, is usually a “bad” signal, reflecting some dysfunction of the system that fails to inhibit the pain and allows it to go on.
A common question that pain researchers face is why similar diseases or injuries cause varying pain levels in different people. We have come to understand that those living with a balanced pain regulation system are able to better inhibit unnecessary or non-threatening pain messages, while those with an imbalanced system lack this inhibitory capacity and are more susceptible to acute and chronic pains. Research has shown that patients with pain disorders such as migraine, tension-type headache, fibromyalgia, irritable bowel syndrome (IBS), temporomandibular joint disorder (TMD) and osteoarthritis usually have lower ability to inhibit pain.
Individuals living with these chronic pain conditions often rely on over-the-counter (OTC) medications or stronger pharmacological solutions to block unnecessary pain signals. In fact, the global opioid market was sized at $25.4 billion in 2018. However, neither OTCs nor prescription pain medication are ideal for long-term use. Instead of developing more medication combinations for long-term pain management, it is time to rethink how we approach pain modulation altogether. With the advancement of technology in the medical device space, recent technologies are making it possible to treat pain conditions non-invasively.
TREATING PAIN WHERE IT DOESN’T HURT
“Pain inhibits pain” is a time-honored medical observation, where pain in one body site will be perceived as less intensive upon the introduction of another pain at a remote site. The underlying mechanism is the activation of internal inhibitory circuits evoked by the new remote pain that inhibit the original pain. When studying this mechanism in humans, we call this phenomenon “conditioned pain modulation” (CPM), a term that is often used to describe the process of endogenous pain inhibition.
In recent years, consistent data have accumulated demonstrating that CPM is less efficient in patients suffering from chronic pain, especially for those living with an idiopathic pain syndrome. That is, their ability to inhibit the perception of one pain by another is reduced—either as a cause or as a consequence of their chronic pain.
Along the same lines, healthy individuals with efficient CPM are less likely to acquire pain (e.g., after surgery) and vice versa. The pain inhibitory system, as depicted by CPM, is therefore an interesting target for the medical device industry to use it to effectively manipulate the individual’s pain regulation system. This is done by applying a nearly painful stimulus that activates pain inhibition and reduces a clinical pain.
If we take migraine as an example, the application of a stimulus in parallel to the headache onset will generate pain inhibition and reduce—or even block—the attack. It is noted that placing a CPM-triggering stimulus on the head or neck would not work as the pain regulation system will see the stimulus as merely an extension of the original pain.
As a result, the pain regulation system will continue to send out pain signals or even increase them based on pain spatial summation. However, if we place the CPM device in a remote region of the body, away from the head or neck, we can send a stimulus that the pain regulation center will recognize as different from the clinical one, and allow it to induce pain inhibition and consequently reduce the clinical pain. What is most exciting is that clinical studies have shown that the remote placement of CPM is as effective as migraine specific pharmacological therapies.
Armed with this latest research in neuromodulation and pain mechanisms, new options emerge for chronic pain patients. Technologies that will allow us to move away from pharmacological options and provide effective long-term, non-invasive analgesia might replace opioids and other side-effect–generating agents. As our understanding of the body’s varying pain mechanisms evolves, innovative solutions for the various idiopathic pain conditions providing effective long-term relief are within reach.
ABOUT THE AUTHOR(S)
David Yarnitsky is the director of the Department of Neurology at Rambam Health Care Campus, Technion Faculty of Medicine, and editor in chief of PAIN Reports. He serves on the medical advisory board of Theranica, a medical technology company developing electroceuticals for migraine and other pain disorders.