Researchers at
Johnson & Johnson Pharmaceutical Research & Development (J&JPRD) today
announced that they have discovered a new molecular mechanism that may
underlie neuropathic pain. The clearer understanding of the root-cause of
chronic neuropathic pain, and the preclinical validation of new targets for
pharmaceutical therapies shown in this research, together present an
opportunity for the development of new ways to treat the severe pain
associated with such common conditions or diseases as sciatica, diabetic
neuropathy and shingles.
This research was presented at
Neuroscience 2006, the annual meeting of the Society for Neuroscience.
Neuropathic pain, or the
spontaneous pain and abnormal sensitivity following a nerve injury,
typically results from a traumatic injury, an infection or disease, or
surgery, and can persist long after the initial injury has healed. Millions
of people worldwide suffer some form of neuropathic pain, and the current
treatment options are limited or inadequate for many people. The research
presented today suggests that the persistent pain may be caused by specific
types of ion channels, called "pacemaker channels," which initiate a
constant and rhythmic transmission of pain signals to the brain,
rhythmically similar to those generated by pacemaker cells that regulate
one's heart rate.
"What we have shown in our early
preclinical research is that we can inhibit the inappropriate neuronal
activity and resulting sensitivity that follows nerve injury," said Alan
Wickenden, Ph.D., Research Fellow in the Pain and Related Disorders Team at
J&JPRD. "Trauma to nerves and the tissues that surround them seems to
trigger a complicated cascade of events that results in an increase in the
activity of these pacemaker ion channels and the resulting transmission of
pain signals to the brain. We are encouraged by early evaluations of certain
chemical structures that seem to disrupt this rhythmic transmission."
Ion channels are openings that
exist within a cell that allow the passage of certain ions into a cell to
regulate activity. It is believed that hundreds of different types of ion
channels exist in the body, each with a distinct responsibility for sending
a specific message, and that specific pacemaker channels exist in peripheral
nerves as well as in the heart and the central nervous system. In the heart,
for instance, signals generated by pacemaker channels stimulate the heart
muscle to contract, and in the brain, they control sleep and waking. Made up
of glycoproteins, or proteins with sugar molecules attached, pacemaker
channels -- also known as HCN channels (Hyperpolarization activated, Cyclic
Nucleotide-gated cation channels) -- allow the entrance of sodium ions into
the cell based on the configuration of the protein. Entry of sodium ions can
trigger electrical activity in both cardiac cells and neurons.
"We think we have only scratched
the surface in this area, as pacemaker channels may also play a role in
inflammatory pain as well as other types, " said Dr. Wickenden. "More
research is needed before this will translate to patient benefit, but the
better understanding we've gained of the mechanism can enable us to narrow
our focus."
About Johnson & Johnson
Pharmaceutical Research & Development
Johnson & Johnson Pharmaceutical
Research & Development (J&JPRD) is part of Johnson & Johnson, the world's
most broad-based producer of health care products. J&JPRD is headquartered
in Raritan, NJ (USA), and has facilities throughout Europe and the United
States. The company is leveraging drug discovery and drug development in a
variety of therapeutic areas to address unmet medical needs worldwide.