Lindsey A. Criswell, M.D., M.P.H., D.Sc.

Lindsey A. Criswell, M.D., M.P.H., D.Sc.

Dear Colleagues,

Understanding and treating joint pain is important to improving long-term health—and a fundamental part of the NIAMS mission. With that imperative in mind, I’m delighted that NIAMS is supporting a new Consortium that may lead us closer to ultimately being able to restore joint health. The Restoring Joint Health and Function to Reduce Pain (RE-JOIN) Consortium is part of the Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative®, an aggressive, trans-NIH effort to speed scientific solutions to stem the national opioid public health crisis. Launched in April 2018, the initiative is focused on improving prevention and treatment strategies for opioid misuse and addiction, and enhancing pain management.

RE-JOIN will bring together multiple research teams to create 3-D maps of the different types of sensory neurons found in two important joints of the body: the knee and the temporomandibular joint (TMJ), better known as the jaw joint. This research aims to discover how neurons from these different joints influence and create the sensation of pain, which could potentially lead to novel, more precise therapies for reducing joint pain and deterioration—as well as restoring healthy joints.

Importantly, joint pain is often cited as a contributing factor by a majority of those living with opioid use disorder. By understanding how nerves are distributed throughout the different tissues of the joint (e.g., innervation) and using that information to develop more effective therapies, we can potentially reduce the burden of opioid dependency and eventually help bring an end to the opioid epidemic.

The five newly awarded projects provide a unique balance and focus on the knee – one of the most stressed joints in the body – and the TMJ, one of the most understudied joints in the body. All of these projects will use cutting-edge technologies, unique methodologies, and a broad array of animal models and human samples to help develop the 3-D innervation maps, which in turn may serve as a blueprint for future research on the innervation of other joints. 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.

The RE-JOIN Consortium will leverage two data management cores within the NIH Common Fund’s Stimulating Peripheral Activity to Relieve Conditions (SPARC) program, which specializes in the innervation of the soft organs. These cores will serve as RE-JOIN coordinating centers for data and visualization.

The RE-JOIN awards are five-year awards funded by the NIH HEAL Initiative, and NIAMS – the principal NIH institute funding research related to musculoskeletal diseases – will administer them. Other NIH Institutes and Centers participating in the RE-JOIN Consortium include: the National Center for Complementary and Integrative Health; the National Institute of Biomedical Imaging and Bioengineering; the National Institute of Dental and Craniofacial Research; the National Institute of Neurological Disorders and Stroke; and the National Institute on Aging.

Understanding and mapping the innervation of joints is only the first step towards developing targeted therapies that can help reduce and potentially eliminate opioid dependency. I am eager to see how RE-JOIN may transform the treatment of joint pain and the maintenance of joint health.

The 2022 RE-JOIN Awardees are:

Anne-Marie Malfait; Martin K. Lotz; and Richard J. Miller Rush University Medical Center Mapping the Joint-Nerve Interactome of the Knee

Armen N. Akopian; Mario Danilo Boada; Malin Ernberg; and Lindsey J. MacPherson

University of Texas Health Science Center Comprehensive Functional Phenotyping of Trigeminal Neurons Innervating Temporomandibular Joint (TMJ) Tissues in Male, Female and Aged Mice, Primates, and Humans With and Without TMJ Disorders (TMJD)
Brendan Lee; Benjamin R. Arenkiel; Russell S. Ray; and Joshua D. Wythe Baylor College of Medicine Neural Anatomy, Connectivity, and Phenotypic Innervation of the Knee Joint
Christopher Ryan Donnelly; Dawen Cai; and Joshua James Emrick Duke University Neural Architecture of the Murine and Human Temporomandibular Joint
Kyle D. Allen and Alejandro Jose Almarza University of Florida Innervation of the Knee and TMJ

Lindsey A. Criswell, M.D., M.P.H., D.Sc.
Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases