Alejandro Almarza, PhDJoint pain can be difficult to manage. Learning more and having a better understanding of how pain works will improve how clinicians can help manage and reduce joint pain.

McGowan Institute for Regenerative Medicine affiliated faculty member Alejandro Almarza, PhD (pictured), Associate Professor in Oral Biology in the School of Dental Medicine at the University of Pittsburgh with a secondary appointment in the Department of Bioengineering, was awarded a $5.9M Restoring Joint Health and Function to Reduce Pain (RE-JOIN) Consortium Project (1UC2AR082196-01) from the National Institutes of Health. The project entitled, “Innervation of the Knee and the Temporomandibular Joint (TMJ),” is part of the Helping to End Addiction Long-term (HEAL) Initiative. This multi-principal investigator award with Dr. Almarza at Pitt and Dr. Kyle Allen at the University of Florida is accepted for three years with potential additional funding for two more years.

Nerve innervation to a joint is a complex network of different neural subtypes that vary between each different anatomical site, such as the knee or the TMJ and also vary with different biological factors (i.e., age, sex, disease) that the patient has. Moreover, to have clinical relevance, a shift in innervation must relate to a shift in symptoms. Our research proposal looks at joint pain from this perspective, generating pathology-pain relationships that are important to clinicians working with patients facing TMJ and knee osteoarthritis (OA) pain.

Teams at Pitt and the University of Florida will work to identify cell bodies in the dorsal root ganglia and trigeminal ganglia that project to the muscle, bone, or intra-articular joint tissues. These neurons will then be evaluated for their function using electrophysiologic tests and their transcriptome using single cell RNA-sequencing. By overlapping neural function with gene expression, they will identify promoter targets and design adeno-associated virus (AAV) vectors to produce fluorescent labels alongside the expression of these targets. Importantly, this approach will allow them to develop AAV-based tracers for specific functional neural subtypes, as well as combine traditional markers of functional subtypes with any newly identified markers that describe how the neuron changes with age, sex, and OA severity. Moreover, these tracers will be used to evaluate how joint innervation adapts following the application of two neural ablation techniques for pain relief in the knee and TMJ. To evaluate the clinical significance of these preclinical studies, innervation changes will be assessed in tissues collected from patients undergoing total joint replacement of the knee or TMJ. In all of these studies, joint innervation will be paired with detailed analyses of joint pain and disability. These analyses will include detailed behavioral characterizations; in patients, these analyses will include quantitative sensory tests and other assessments of joint function. Combined, this approach will allow them to evaluate pathology-pain relationships related to joint innervation from the preclinical model to the clinic.

The consortium project comprises 5 national teams bringing synergistic expertise about the types and distribution of neurons in joint tissues to identify key receptors and mediators that induce pain by activating specific sensory neurons. The Pitt team—under the direction of Dr. Almarza—will focus on the TMJ, and Dr. Allen will lead the work on the knee.

Congratulations, Dr. Almarza!

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University of Pittsburgh School of Dental Medicine News Release