NIH Backs Non-Opioid Pain Relief Research for Oral Cancer Patients

Significant NIH Grant Awarded to UT Health San Antonio for Pain Relief Research

USA: The School of Dentistry at The University of Texas Health Science Center at San Antonio (UT Health San Antonio) has received a significant research grant from the National Institutes of Health (NIH) aimed at developing new pain relief strategies for patients suffering from head and neck carcinoma. This grant, totaling nearly $600,000, is the first awarded under UT Health San Antonio’s newly established Center for Pain Therapeutics and Addiction Research. As reported by News Medical, the NIH’s National Institute of Dental and Craniofacial Research funded this grant to tackle the pressing need for effective, non-opioid pain relief methods for oral cancer patients.

Shivani Ruparel, PhD, an associate professor of endodontics at UT Health San Antonio and the principal investigator of the study, emphasized the urgency of this research, stating, “It is often very difficult to treat pain from oral cancer with available medications due to limited effectiveness or rapid development of tolerance.” The innovative study seeks to explore new mechanisms for managing pain in cancer patients, aiming to enhance both pain management and potentially the treatment of the cancer itself.

Multidisciplinary Approach to Address Pain and Addiction

The Center for Pain Therapeutics and Addiction Research, which began operations in June this year, represents a transformative approach to pain management, addressing both the underlying mechanisms of pain and developing therapies to reduce or block its transmission. The center focuses not only on pain related to oral cancer but also other forms of pain, aiming to develop therapies that do not rely on addictive substances.

The range of proposed therapies includes novel, non-addictive medications, dietary and nutritional modifications, as well as alternative therapies. Kenneth M. Hargreaves, DDS, PhD, professor of endodontics at UT Health San Antonio and director of the Center, stated, “This important NIH grant will support the groundbreaking research of Dr. Shivani Ruparel who is leading efforts towards novel mechanisms of orofacial pain and its treatment. By expanding our knowledge of pain biology, we can leverage these findings into tomorrow’s new medications.”

Understanding and Targeting Oral Cancer Pain Mechanisms

Pain remains the primary symptom driving oral cancer patients to seek medical care. It starts with the development of the tumor and worsens as the disease progresses, significantly impacting the patient’s quality of life. Unfortunately, traditional methods of pain management are often insufficient for these patients, making it crucial to explore new pathways for relief.

The study led by Ruparel focuses on understanding these pain mechanisms, with the goal of developing novel, non-opioid analgesics that can effectively relieve pain without the side effects associated with opioid use. One target of this research is the role of tyrosine kinase receptors, a group of proteins located on the surface of cells that play a key role in many cellular functions. Specifically, the brain-derived neurotrophic factor (BDNF), a protein important for cognitive performance, and its tyrosine kinase receptor have been found to be overexpressed in oral tumors, contributing to cancer progression.

Ruparel’s team has demonstrated for the first time that this pathway not only promotes tumor growth but also drives the pain associated with oral cancer. The researchers have found that BDNF released from oral squamous cell carcinoma cells influences pain transmission, and this effect can be reversed by inhibiting the receptor at the site of the tumor. This discovery suggests that the receptor could be a viable target for treating oral cancer pain without the side effects commonly linked to opioids.

Investigating New Therapeutic Targets

According to Ruparel, the research will delve further into the role of the truncated receptor isoform of BDNF, which appears to be the predominant type in trigeminal sensory neurons—responsible for pain signals from the head and face—as well as in oral squamous cell carcinoma cells. The study will examine how this receptor impacts pain behaviors, neuronal plasticity, and gene expression. Additionally, the research will assess whether the receptor derived from cancer cells regulates pain-associated changes in the tumor microenvironment, including immune cell profiles and transcriptomic changes.

“This study’s relevance lies in its potential to uncover novel therapeutic targets for managing oral cancer-induced pain and improving patients’ quality of life,” Ruparel noted. By targeting this receptor, there is potential to not only alleviate cancer-induced pain but also to slow tumor progression. “Given that this isoform contributes to tumor progression, targeting this receptor signaling can prove to be effective therapy for cancer-induced pain as well as tumor progression,” she added.

Implications for Patient Care

The research conducted by Ruparel’s team has broad implications for patients struggling with oral cancer. Peter M. Loomer, DDS, PhD, MBA, professor and dean of the UT Health San Antonio School of Dentistry, highlighted the significance of this work for the local community. “Oral cancer is a significant health issue in South Texas, and Dr. Ruparel works towards improving the quality of life of those suffering from this devastating disease,” Loomer stated.

The NIH’s support of this study represents a major step forward in the quest for non-addictive pain relief for cancer patients, offering hope for improved quality of life and more effective treatment options.