Key cellular mechanism behind the onset of tinnitus identified
16 May 2012
Research into hearing loss after exposure to loud noises could
lead to the first drug treatments to prevent the development of tinnitus
Researchers in the University of Leicester's Department of Cell
Physiology and Pharmacology have identified a cellular mechanism
that could underlie the development of tinnitus following exposure
to loud noises.
The discovery could lead to novel tinnitus treatments, and
investigations into potential drugs to prevent tinnitus are
Tinnitus is a sensation of phantom sounds, usually ringing or
buzzing, heard in the ears when no external noise is present. It
commonly develops after exposure to loud noises (acoustic
over-exposure), and scientists have speculated that it results from
damage to nerve cells connected to the ears.
Although hearing loss and tinnitus affect around 10% of the
population, there are currently no drugs available to treat or
University of Leicester researcher Dr Martine Hamann, who led the
study published in the journal Hearing Research, said: "We
need to know the implications of acoustic over exposure, not only in
terms of hearing loss but also what's happening in the brain and
central nervous system. It's believed that tinnitus results from
changes in excitability in cells in the brain — cells become more
reactive, in this case more reactive to an unknown sound."
Dr Hamann and her team, including PhD student Nadia Pilati,
looked at cells in an area of the brain called the dorsal cochlear
nucleus — the relay carrying signals from nerve cells in the ear to
the parts of the brain that decode and make sense of sounds.
Following exposure to loud noises, some of the nerve cells (neurons)
in the dorsal cochlear nucleus start to fire erratically, and this
uncontrolled activity eventually leads to tinnitus.
Dr Hamann said “We showed that exposure to loud sound triggers
hearing loss a few days after the exposure to the sound. It also
triggers this uncontrolled activity in the neurons of the dorsal
cochlear nucleus. This is all happening very quickly, in a matter of
In a key breakthrough in collaboration with GSK who sponsored Dr
Pilati’s PhD, the team also discovered the specific cellular
mechanism that leads to the neurons' over-activity. Malfunctions in
specific potassium channels that help regulate the nerve cell's
electrical activity mean the neurons cannot return to an equilibrium
Ordinarily, these cells only fire regularly and therefore
regularly return to a rest state. However, if the potassium channels
are not working properly, the cells cannot return to a rest state
and instead fire continuously in random bursts, creating the
sensation of constant noise when none exists.
Dr Hamann explained: "In normal conditions the channel helps to
drag down the cellular electrical activity to its resting state and
this allows the cell to function with a regular pattern. After
exposure to loud sound, the channel is functioning less and
therefore the cell is constantly active, being unable to reach its
resting state and displaying those irregular bursts.”
Although many researchers have investigated the mechanisms
underlying tinnitus, this is the first time that cellular bursting
activity has been characterised and linked to specific potassium
channels. Identifying the potassium channels involved in the early
stages of tinnitus opens up new possibilities for preventing
tinnitus with early drug treatments.
Dr Hamann's team is currently investigating potential drugs that
could regulate the damaged cells, preventing their erratic firing
and returning them to a resting state. If suitable drug compounds
are discovered, they could be given to patients who have been
exposed to loud noises to protect them against the onset of
These investigations are still in the preliminary stages, and any
drug treatment would still be years away.
The research was funded by a Research Councils UK fellowship to
Dr Hamann, a grant from the Wellcome Trust and a PhD studentship
from GlaxoSmithKline, with follow-up investigations funded by a
three-month grant from Deafness Research UK. Further pharmaceutical
research will be carried out by the University of Leicester in
collaboration with Autifony Therapeutics Ltd via a Medical Research
Council Case studentship due to start in October 2012.
Vivienne Michael, Chief Executive of Deafness Research UK, said
"We’re pleased to hear about this progress in such a debilitating
hearing impairment. The charity continues to fund research into
better treatments for tinnitus, with the ultimate aim of a cure. Our
free information leaflets offer immediate help to sufferers and our
national helpline provides additional support. Regularly tinnitus
generates the most requests for help."