Posted September 5, 2023

From re-examining previously abandoned ideas to making the most of big data, the researchers funded by the fiscal year 2021 (FY21) Spinal Cord Injury Research Program (SCIRP) push the boundaries of innovation by exploring new avenues to bring therapeutics to those living with spinal cord injury (SCI), their loved ones, caregivers, and physicians. One Focus Area, SCI-related pain, has funded researchers who are innovative not only in their research questions, but also in their approach to research. These projects address pain after SCI, from inception through treatment, with the ultimate goal of optimizing neuropathic pain care.

Waiting for the Right Time

Never one to let a good idea go, Dr. Jaqueline Sagen’s (University of Miami) research interests lay in using cell-based therapy for pain mitigation. Nearly 40 years ago, her group studied chromaffin cells (derived from the adrenal gland, which sits on top of the kidneys) because they produce analgesic molecules that act as natural pain reducers in the body. When added to the spinal fluid of animal models, these cells act as “mini pumps” of local, self-producing, pain relief. There was just one problem: Dr. Sagen could not obtain enough of these cells to make it a viable treatment for pain in patients, and the project was shelved. Fast forward to the pioneering discovery by Dr. Shinya Yamanaka and colleagues of induced pluripotent stem cells (iPSCs, cells turned from one type into another type of cell) and the subsequent fine-tuning of this breakthrough technology, and Dr. Sagen saw her chance to dust off the chromaffin cell idea and take it off the shelf. Now equipped with an FY21 SCIRP Investigator-Initiated Research Award, Dr. Sagan looks to capitalize on the iPSC process to make patient-specific chromaffin cells as the first step in developing this novel, personalized medicine approach for SCI neuropathic pain management.

Partnerships in the Modern Research Community

Scientific collaborations are a hallmark of modern research that bring together scientists with complementary skills and research interests to jointly tackle complex modern medical questions. Dr. Jacob McPherson (Washington University, St. Louis) and Dr. Aiko Thompson (Medical University of South Carolina) are collaborating on an FY21 SCIRP Translational Research Award to explore how employing neurobehavioral training to rewire spinal pain pathways can be instrumental in reducing SCI-related neuropathic pain. These separate but collaborative projects meld Dr. McPherson’s expertise in neuronal motor control and neural plasticity (the ability of the nervous system to adapt to stimuli) with Dr. Thompson’s background in central nervous system plasticity and sensorimotor function (how the body moves in reaction to stimuli) to explore rewiring spinal pain pathways in persons living with SCI. Simultaneously performing studies in rats (McPherson) and people (Thompson) will allow these partnering principal investigators to continuously adjust to one another’s results in real time as they identify the components of reflexes in the skin that cause pain. This project will then culminate in a translationally informed pilot clinical trial utilizing peripheral nerve stimulation in participants with SCI to reduce neuropathic pain.

Making the Most of Big Data

From databases and algorithms to biorepositories, the sheer volume of data that scientists now have at their disposal is staggering. With an FY21 SCIRP Investigator-Initiated Research Award, Dr. Nikolaos Kyritsis (University of California, San Francisco) is taking advantage of this large wealth of information to tackle an urgent need in the wider pain management field: identification of non-opioid solutions to treat pain. This innovative project will start by developing a mathematical model aimed at identifying biomarkers that can predict the future development of chronic neuropathic pain in persons living with SCI. His team will utilize the TRACK-SCI database – an ongoing collaborative clinical research study that collects demographics, treatment, and outcomes data, along with participant biospecimens such as blood samples – to conduct this population-wide biomarker analysis. Dr. Kyritsis and his team will utilize this new model to identify targets of non-opioid chemicals that are highly expressed in blood cells from patients who develop chronic SCI-related pain. The power to leverage existing big data repositories to examine population-level trends has real potential to lead to more informed decision-making related to care and the development of new and safer options to treat pain in patients across all fields of medicine.

Capitalizing on their strengths while utilizing the latest in science and technology, these researchers are diving head-first into the world of pain management alternatives. Seeking new and creative avenues of research, looking at data in new ways, and forming unique partnerships will allow these researchers to identify and optimize non-opioid pain relief options. While neuropathic pain is one of the most cited daily challenges for those living with SCI (Anderson, 2004), others who suffer from conditions such as diabetes, viral infections, and amputation often report associated neuropathic pain symptoms (Colloca, 2017). This emphasizes the broad applicability and huge potential impact on patient care and quality of life for innovative and out-of-the-box thinking on this important issue, with the FY21 SCIRP researchers rising to the challenge.

Links:

Public and Technical Abstracts: Alleviation of Chronic SCI Neuropathic Pain Using Novel Engineered Human iPSC-Derived Chromaffin Cell Grafts

Public and Technical Abstracts: Targeted Spinal Cord Plasticity for Alleviating SCI-Related Neuropathic Pain

Public and Technical Abstracts: Using Big Data and Machine Learning Approaches to Discover Prognostic Biomarkers and Drugs for Neuropathic Pain in Chronic SCI

References:

Anderson KD. 2004. Targeting recovery: Priorities of the spinal cord-injured population. J Neurotrauma 21(10):1371-83.

Colloca L, Ludman T, Bouhassira D, et al. 2017. Neuropathic pain. Nature Reviews Disease Primers 3:17002.

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Last updated Tuesday, September 5, 2023