History of Tinnitus

Phantom auditory perception--tinnitus--is a symptom of many pathologies. Although there are a number of theories postulating certain mechanisms of its generation, none have been proven yet. This paper analyses the phenomenon of tinnitus from the point of view of general neurophysiology. Existing theories and their extrapolation are presented, together with some new potential mechanisms of tinnitus generation, encompassing the involvement of calcium and calcium channels in cochlear function, with implications for malfunction and aging of the auditory and vestibular systems. It is hypothesized that most tinnitus results from the perception of abnormal activity, defined as activity which cannot be induced by any combination of external sounds. Moreover, it is hypothesized that signal recognition and classification circuits, working on holographic or neuronal network-like representation, are involved in the perception of tinnitus and are subject to plastic modification. Furthermore, it is proposed that all levels of the nervous system, to varying degrees, are involved in tinnitus manifestation. These concepts are used to unravel the inexplicable, unique features of tinnitus and its masking. Some clinical implications of these theories are suggested.

Tinnitus, the most common auditory disorder, affects about 40 million people in the United States alone, and its incidence is rising due to an aging population and increasing noise exposure. Although several approaches for the alleviation of tinnitus exist, there is as of yet no cure. The present article proposes a testable model for tinnitus that is grounded in recent findings from human imaging and focuses on brain areas in cortex, thalamus, and ventral striatum. Limbic and auditory brain areas are thought to interact at the thalamic level. While a tinnitus signal originates from lesion-induced plasticity of the auditory pathways, it can be tuned out by feedback connections from limbic regions, which block the tinnitus signal from reaching auditory cortex. If the limbic regions are compromised, this "noise-cancellation" mechanism breaks down, and chronic tinnitus results. Hopefully, this model will ultimately enable the development of effective treatment.

Current analgesics predominately modulate pain transduction and transmission in neurons and have limited success in controlling disease progression. Accumulating evidence suggests that neuroinflammation, which is characterized by infiltration of immune cells, activation of glial cells and production of inflammatory mediators in the peripheral and central nervous system, has an important role in the induction and maintenance of chronic pain. This Review focuses on emerging targets - such as chemokines, proteases and the WNT pathway - that promote spinal cord neuroinflammation and chronic pain. It also highlights the anti-inflammatory and pro-resolution lipid mediators that act on immune cells, glial cells and neurons to resolve neuroinflammation, synaptic plasticity and pain. Targeting excessive neuroinflammation could offer new therapeutic opportunities for chronic pain and related neurological and psychiatric disorders.