Identification of temporomandibular joint innervating somatosensory neurons by retrograde labeling and multiplexed imaging mass cytometry

Researcher(s)

  • Daivik Arora, Biological Sciences, University of Delaware

Faculty Mentor(s)

  • Austin Keeler, Biological Sciences, University of Delaware

Abstract

The brain builds circuits that translate stimuli into appropriate behavioral responses: however, problems such as osteoarthritis can lead to dysfunctional pain sensations, like in chronic pain conditions. The breakdown of tissue in joints, known as osteoarthritis, occurs over time and causes changes in the excitability of joint innervating neurons (JINs) resulting in chronic and neuropathic pain. For instance, recent work shows that headaches and other persistent pain across the head that are common in temporomandibular disease (TMD) often result from osteoarthritis of the temporomandibular joint, or jaw. Pain sensation is transmitted by neurons of the trigeminal ganglion, on the trigeminal nerve, that innervates the face. While some of the neurons in the trigeminal ganglia innervate the jaw, many do not, and the identity or molecular profile of neurons that innervate different facial targets is not known. Further, it is also unknown how JINs, as opposed to other neurons in the trigeminal ganglia, respond to the progression of osteoarthritis. Here, we seek to develop a system to retrogradely label temporomandibular joint innervating neurons in the trigeminal ganglia by injections of light-excited and/or metal-tagged wheat germ agglutin (WGA) to mark the JINs. There are 18 somatosensory populations that comprise the JINs, for which traditional measures can only identify general types or a few at a time, warranting the use of imaging mass cytometry (IMC). IMC is a protein-based, multiplexed spatial technology that detects over 40 antibodies simultaneously. By combining WGA-labeling and IMC, we can investigate the spatial distribution and relative abundance of all adult somatosensory neuron populations. Once this workflow is validated, we will use IMC on the TG with the JINs labeled to understand the molecular changes across OA.