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In the October issue of Trends in Cognitive Sciences, researchers say identifying the problem is the first step to developing effective therapies for these disorders, which afflict millions of people. None now exist.

The scientists describe how the neural mechanisms that normally 鈥済ate鈥� or control noise and pain signals can become dysfunctional, leading to a chronic perception of these sensations. They traced the flow of these signals through the brain and showed where 鈥渃ircuit breakers鈥� should be working 鈥� but aren鈥檛.

In both disorders, the brain has been reorganized in response to an injury in its sensory apparatus, says Josef Rauschecker, PhD, DSc, director of the Laboratory for Integrative Neuroscience and Cognition at GUMC. Tinnitus can occur after the ears are damaged by loud noise, but even after the brain reorganizes itself, it continues to 鈥渉ear鈥� a constant hum or drum. Chronic pain can occur from an injury that often is healed on the outside but persists inside the brain.

鈥淪ome people call these phantom sensations, but they are real, produced by a brain that continues to 鈥榝eel鈥� the initial injury because it cannot down-regulate the sensations enough,鈥� he says. 鈥淏oth conditions are extraordinarily common, yet no treatment gets to the root of these disorders.鈥�

Areas of the brain responsible for these errant sensations are the nucleus accumbens, the reward and learning center, and several areas that serve 鈥渆xecutive鈥� or administrative roles 鈥攖he ventromedial prefrontal cortex (VNPFC) and the anterior cingulate cortex.

All of these areas are also important for evaluating and modulating emotional experiences, Rauschecker says. 鈥淭hese areas act as a central gatekeeping system for perceptual sensations, which evaluate the affective meaning of sensory stimuli 鈥� whether produced externally or internally 鈥� and modulates information flow in the brain. Tinnitus and chronic pain occur when this system is compromised.鈥�

Other issues often arise in 鈥渓ockstep鈥� with tinnitus and/or chronic pain, such as depression and anxiety, which are also modulated by the nucleus accumbens, he says. Uncontrollable or long-term stress is another important factor.

Ironically, the brain plasticity that produces some of these changes provides hope that this gatekeeping role can be restored, Rauschecker says. Because these systems rely on transmission of dopamine and serotonin between neurons, drugs that modulate dopamine may help restore sensory gating, he says.

鈥淏etter understanding could also lead to standardized assessment of individuals' risk to develop chronic tinnitus and chronic pain, which in turn might allow for earlier and more targeted treatment,鈥� adds Markus Ploner, MD, PhD, a consultant neurologist and Heisenberg Professor of Human Pain Research at the Technische Universit盲t M眉nchen (TUM).

Rauschecker, an expert in tinnitus, collaborated with Ploner, who studies chronic pain, during his senior fellowship at the Institute of Advanced Study at TUM. Co-authors include Audrey Maudoux, MD, PhD, from GUMC and Elisabeth May, PhD, from TUM.

The National Institutes of Health (RC1-DC010720), the American Tinnitus Association, the Skirball Foundation, the Tinnitus Research Initiative and the Tinnitus Research Consortium have supported tinnitus research in the Rauschecker lab.

About Georgetown University Medical CenterGeorgetown University Medical Center (GUMC) is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC鈥檚 mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization, which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health.###