{"id":3555,"date":"2025-02-07T14:00:56","date_gmt":"2025-02-07T14:00:56","guid":{"rendered":"https:\/\/magazines.uthscsa.edu\/schools\/?p=3555"},"modified":"2025-02-12T21:20:30","modified_gmt":"2025-02-12T21:20:30","slug":"looking-beyond-opioids","status":"publish","type":"post","link":"https:\/\/magazines.uthscsa.edu\/schools\/2025\/02\/07\/looking-beyond-opioids\/","title":{"rendered":"Looking beyond opioids"},"content":{"rendered":"

A new Center for Pain Therapeutics and Addiction Research will position the school as a multidisciplinary leader revolutionizing pain treatment and addiction management<\/strong><\/h2>\n

By Jessica Binkley Lain<\/em><\/p>\n

Pain management is not a new challenge for dentists. Teeth are composed of some of the most highly innervated tissues in the body, and the mouth is a region vulnerable to infection, so dentists must often contend with extreme patient pain during treatment.<\/p>\n

\"Kenneth
Kenneth Hargreaves, DDS, PhD, is the inaugural director of the Center for Pain Therapeutics and Addiction Research.<\/figcaption><\/figure>\n

\u201cDentists have become, by necessity, experts in terms of diagnosing and treating inflammatory pain, so there\u2019s a long history in the discipline,\u201d said Kenneth Hargreaves, DDS, PhD<\/a>, professor of endodontics and a world-renowned expert in pain research. \u201cTo that end, the School of Dentistry has been advancing pain research to improve pain management for over 20 years.\u201d<\/p>\n

In an innovative move to put the School of Dentistry\u2019s<\/a> research efforts on the global stage, the school recently launched its Center for Pain Therapeutics and Addiction Research<\/a>, appointing Hargreaves to serve as the center\u2019s inaugural director in August 2024.<\/p>\n

The new center brings together experts across disciplines to increase the understanding of the basic mechanisms of pain, as well as to shed light on addiction.<\/p>\n

\u201cThe University of Texas Health Science Center at San Antonio has long been recognized internationally for its groundbreaking work in addiction and substance use disorder,\u201d Hargreaves noted. \u201cWe see this new center as a complement to this established expertise of the university and a natural progression of all the research and training efforts our school has been involved in over the years.\u201d The center has members from multiple departments within the dental school and is actively recruiting faculty from across the university. The center already hosts two members from the Joe R. and Teresa Lozano Long School of Medicine\u2019s Department of Pharmacology, signaling its interdisciplinary and collaborative approach to pain and addiction research.<\/p>\n

A major focus of the center is basic science research that will lead to the development of novel, non-opioid analgesics.<\/p>\n

Currently, explorations into pain caused from specific conditions, such as temporomandibular joint disorders and oral cancer, aim to understand the underlying mechanisms that contribute to pain and to discover potential targets for future drug development.<\/p>\n

Targets for oral cancer pain<\/strong><\/h3>\n
\"Shivani
Shivani Ruparel, PhD, seeks safer and more effective pain treatments.<\/figcaption><\/figure>\n

\u201cWhen people think about cancer, they often think of chemotherapy or the disease progression, but cancer pain is its own unique challenge that needs more attention in cancer and pain research,\u201d said Shivani Ruparel, PhD<\/a>, associate professor in the Department of Endodontics.<\/p>\n

Ruparel has focused her research career on oral cancer, which she described as being particularly painful. Unlike other cancers such as breast or prostate cancer, which typically only cause pain when metastasized to the bone, oral cancer induces pain as soon as the tumor begins to grow, even when it is small, she explained.<\/p>\n

\u201cPatients with oral cancer experience pain from the start, and unfortunately, the main treatment option is opioids,\u201d she said.<\/p>\n

This opioid reliance, she noted, presents several issues. Oral cancer patients often develop tolerance to opioids quickly, and there is evidence that opioids can promote cancer progression.<\/p>\n

\u201cIt\u2019s a devastating cycle. Not only do these patients endure pain, but their pain treatments may also be worsening their condition,\u201d Ruparel said.<\/p>\n

Oral cancer is the sixth most common cancer globally, affecting 400,000 to 600,000 people annually. However, it receives less attention and research funding than cancers like breast and prostate cancer. Moreover, treatment options for oral cancer are successful in only about 50% of cases, Ruparel said.<\/p>\n

\u201cThese patients are suffering a lot of pain, so we need more research in pain management for these patients, especially into non-opioid treatments,\u201d said Ruparel.<\/p>\n

She studies how tumors interact with sensory nerves, focusing on where the pain is produced at the site of the tumor. Her team is particularly interested in a protein called brain-derived neurotrophic factor, or BDNF, and its receptor, TrkB \u2014 both of which are highly expressed in oral tumors.<\/p>\n

\u201cWe discovered that targeting BDNF and TrkB not only slows tumor progression but also reduces pain,\u201d Ruparel explained. \u201cThis is a hugestep forward because it means we can potentially treat the cancer and the pain simultaneously.\u201d<\/p>\n

Ruparel is excited about the new center, particularly for its promise for discovering non-opioid solutions to pain.<\/p>\n

\u201cThe opioid crisis has made treating chronic pain even more complex,\u201d she noted. \u201cThis center is a significant step forward, not just for the School of Dentistry and the university, but for the global pain research community.\u201d<\/p>\n

\"Nikita
Nikita Ruparel, DDS, PhD, studies the effects of stem cell-released factors to alleviate pain.<\/figcaption><\/figure>\n

Potential of stem cells<\/strong><\/h3>\n

Stem cells are another exciting area of research, with a potential for non-opioid analgesic drug development. Among the scientists driving this progress is Nikita Ruparel, MS, DDS, PhD<\/a>, associate professor and sister to Shivani Ruparel in the Department of Endodontics, and a researcher at the new center. Nikita Ruparel and her team are researching the mechanisms by which stem cells can inhibit oral facial pain.<\/p>\n

\u201cHaving worked on tissue regeneration with stem cells as a postdoc, I had a great understanding of how stem cells function and what their capabilities are as a therapeutic class,\u201d Nikita Ruparel explained. \u201cSo, I asked myself, if stem cells are so powerful in modulating the immune response and providing regeneration, why don\u2019t we have more literature on their effects on pain management?\u201d<\/p>\n

This curiosity led Nikita Ruparel to explore the use of stem cells in treating dental pain, specifically in a condition called apical periodontitis, a common inflammatory disease caused by tooth infection.<\/p>\n

By injecting human stem cells into mice with the condition, she and her team found that the pain thresholds in the mice returned to normal following the stem cell injections. This was an exciting discovery, showing that stem cells could significantly impact pain responses, said Nikita Ruparel.<\/p>\n

By injecting stem cells into the mouse models, the team was able to observe a complete reversal of pain after 21 days. The tests included assessing sensitivity around the affected area of the mouse\u2019s face, as well as tracking the spontaneous pain response through behavioral experiments.<\/p>\n

\u201cWe found that stem cells actually migrate directly to the site of tooth injury,\u201d Nikita Ruparel revealed. This homing mechanism, known as chemotaxis, allows the stem cells to move toward injured tissues that release specific factors, drawing them in. Once there, the stem cells not only aid in tissue repair, but also inhibit pain.<\/p>\n

\u201cThe factor SDF-1, or stromal-derived factor 1, is six times more present at an injured site compared to healthy tissue,\u201d Nikita Ruparel. explained. \u201cStem cells are drawn to these elevated levels of SDF-1, which is why they go directly to the site of injury. This response is something we can mimic without needing to inject stem cells.\u201d<\/p>\n

One of the factors stem cells release is called macrophage migration inhibitory factor, or MMIF, which inhibits pain neurons, said Nikita Ruparel.<\/p>\n

\u201cOur ultimate goal is to take the receptors for MMIF that are present on sensory neurons and use them as drug targets in patients. Instead of injecting stem cells directly into humans, we\u2019re working to create drugs that replicate the effects of the stem cell-released factors to alleviate pain.\u201d<\/p>\n

The center also promises to provide students with unparalleled opportunities.<\/p>\n

\u201cHaving this center will help our students get a more comprehensive experience,\u201d Nikita Ruparel said. \u201cOther scientists within the university will recognize its potential, and we can create a more collaborative environment for mentoring the next generation of pain researchers.\u201d<\/p>\n

Simple diet changes<\/strong><\/h3>\n

Other investigations at the new center are focused on how the role of secondary factors influence the risk of overall pain throughout the body.<\/p>\n

\u201cOne of the center\u2019s investigators is looking at the role of hypoxia in pain,\u201d Hargreaves explained, referring to research by Nathaniel Jeske, PhD<\/a>, director of research for the Department of Oral and Maxillofacial Surgery, who recently published a paper showing that sleep apnea could increase the risk of pain.<\/p>\n

\u201cWe\u2019re even investigating the role of diet in pain management, exploring how dietary changes, rather than drugs, might influence the development of pain,\u201d Hargreaves said.<\/p>\n

For nearly 15 years, Hargreaves and a team of researchers have been studying two classes of lipids \u2014 omega-3 and omega-6 \u2014 and their role in reducing or increasing the risk of pain in the body.<\/p>\n

\u201cYou\u2019ve probably heard of the Mediterranean diet, which emphasizes healthy omega-3 lipids and is widely recognized not only for helping with weight loss, but also for promoting heart health and improving metabolic function,\u201d Hargreaves said. \u201cWhat we\u2019ve discovered is that omega-3 can also help relieve pain. On the other hand, the other class of lipids, omega-6 lipids, we found to be pro-inflammatory. These lipids are found in fried foods, and when your body is filled with omega-6 lipids, it actually leads to a greater pain response after an injury.\u201d<\/p>\n

In laboratory studies with diabetic mouse models, Hargreaves and his team found that feeding them a diet heavy in omega-6 lipids made their diabetic pain much worse. However, when fed a healthy omega-3 lipids diet, their diabetic neuropathy was nearly reversed \u2014 just by changing their diet.<\/p>\n

Recently, Hargreaves received a $1.3 million grant from the U.S. Department of Defense to evaluate the role of omega-3 lipids in treating diabetic pain and second-degree burn injuries.<\/p>\n

\u201cIf we can treat these conditions with simple dietary changes, taking a nutraceutical approach instead of a pharmaceutical approach, not only can we improve patients\u2019 quality of life, but we can also avoid the use of opioids,\u201d he said.<\/p>\n

Training and policy<\/strong><\/h3>\n

In addition to research, education also plays a crucial role in the new center\u2019s mission. Dentists at the predoctoral and graduate levels are being trained in the latest methods for diagnosing and treating pain.<\/p>\n

\u201cOur goal is to help dentists counsel patients who might show signs of substance use disorder, providing appropriate referrals to experts for better care,\u201d said Hargreaves. Shaping policy is another goal of the center, particularly around the responsible prescription of opioids.<\/p>\n

\u201cThe dental school has been at the forefront of developing policies for when and under what conditions to prescribe opioids. While opioids are an important class of drugs, they should not be used in everyday situations,\u201d Hargreaves said. The center advocates for effective pain control without the risks associated with opioid use.<\/p>\n

With a focus on cutting-edge research, education and policy, the Center for Pain Therapeutics and Addiction Research is poised to transform how pain and addiction are understood and treated, not just in dentistry but across health care.<\/p>\n

\u201cWe want to take the university\u2019s motto \u2014 \u2018We make lives better\u2019 \u2014 and make that real,\u201d Hargreaves said. \u201cBy advancing our understanding of pain and addiction, we hope to bring tangible improvements to the lives of our patients and the broader community.\u201d<\/p>\n

\n

Charting Neural Territory<\/strong><\/h2>\n

Mapping neural networks opens a path for non-opioid pain relief<\/strong><\/h3>\n
\"Armen
Armen Akopian, PhD<\/figcaption><\/figure>\n

Joint and muscle pain are often cited as contributing factors to opioid use disorders, said Armen Akopian, PhD<\/a>, professor of endodontics in the School of Dentistry. He is the principal investigator of a study to discover how sensory neurons in the jaw joint and mastication muscles influence and create pain, which could lead to safer drug alternatives to opioid painkillers while helping to curb addiction.<\/p>\n

\u201cThis effort is the basis for eventually developing drugs to replace opioids, so that when someone goes to the dentist with severe jaw joint and facial muscle pain, they will no longer have just one option to control it,\u201d he said.<\/p>\n

Akopian and his team are creating 3D maps of the different types of sensory neurons found in the temporomandibular joint and mastication muscle, better known as the jaw joint structures. In doing so, they will seek to better understand how nerves are distributed, or innervated, throughout the different tissues of the joint. That information, in turn, is expected to be used to develop novel, more precise therapies for reducing joint pain and deterioration as well as restore healthy joints.<\/p>\n

There will also be a focus on understanding how these types and patterns of sensory and sympathetic neuron networks in joints change with disease and aging, and how they differ between individuals depending on age, sex or disease, said Akopian. Understanding and mapping the innervation of joints is an important first step toward developing targeted therapies that can help reduce and potentially eliminate opioid dependency.<\/p>\n","protected":false},"excerpt":{"rendered":"

A revolution in pain exploration has been launched with the school\u2019s new Center for Pain Therapeutics and Addiction Research. Interdisciplinary collaboration is helping investigators study non-opioid treatments for chronic pain and how diet and stem cells can help alleviate suffering.<\/p>\n","protected":false},"author":653,"featured_media":3556,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[12],"magazine":[23],"issue-year":[59],"featured-story":[36,37],"class_list":["post-3555","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-research","magazine-salute","issue-year-59","featured-story-homepage","featured-story-landing-page"],"yoast_head":"\nLooking beyond opioids - Magazines of the Schools at UT Health San Antonio<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/magazines.uthscsa.edu\/schools\/2025\/02\/07\/looking-beyond-opioids\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Looking beyond opioids - Magazines of the Schools at UT Health San Antonio\" \/>\n<meta property=\"og:description\" content=\"A revolution in pain exploration has been launched with the school\u2019s new Center for Pain Therapeutics and Addiction Research. 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