Role of Descending Pain Modulation System in Orofacial Pain

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PROJECT SUMMARY TMD is a prevalent, but poorly understood condition that can be difficult to treat. Many patients with chronic TMD have pain that continues after injury resolution or no obvious underlying tissue damage. Their pain is thus most likely due to dysfunction in central pain processing circuitry. Nociception is the transmission of information about harmful stimuli from the peripheral tissues to the central nervous system. Nociceptive signals are actively regulated by descending pain-modulatory systems, which can either dampen of enhance nociceptive transmission. The rostral ventromedial medulla (RVM) is a major output of the best-studied pain-modulation circuit. RVM modulates nociceptive transmission via two classes of cells, termed “ON-cells” and “OFF-cells.” A third class of cells in RVM, referred to as “NEUTRAL cells,” have no apparent function in pain-modulation. The net effect of RVM output on nociceptive processing in the dorsal horn of the spinal cord has been studied extensively, and shown to be altered in states of persistent pain. However, the changes in ON- and OFF cells, the output of the descending control from RVM, during orofacial inflammation have not been determined. The goal of this proposal is to determine how orofacial inflammation changes the outputs of RVM ON- and OFF-cells. Specifically a masseter muscle inflammation model of myogenous TMD in the rat will be used to achieve this goal. Changes in cell firing evoked by innocuous and noxious mechanical stimulation of orofacial tissues will be quantified using in vivo electrophysiology to test the hypothesis that the force required to elicit an RVM neuronal response will be decreased in animals with masseter inflammation, at the site of inflammation as well as at distant locations (Specific Aim 1). Additionally, light leads to changes in a subset of RVM cells. If the proportion and responsiveness of light sensitive RVM cells increases in states of persistent pain, then light could facilitate pain transmission through RVM. Thus, this project will test the hypothesis that orofacial inflammation will increase light responsiveness of RVM (Specific Aim 2). This work will contribute significantly to our understanding of the neural circuitry changes underlying chronic TMD.