Chronic Pain (cont.)
What is the future of pain research?
In the forefront of pain research are
scientists supported by the National Institutes of Health (NIH), including the NINDS. Other institutes at NIH that support
pain research include the National Institute of Dental and Craniofacial
Research, the National Cancer Institute, the National Institute of Nursing
Research, the National Institute on Drug Abuse, and the National Institute of
Mental Health. Developing better pain
treatments is the primary goal of all pain research being conducted by these
institutes.
Some pain medications dull the patient's perception of
pain. Morphine is one such drug. It works through the body's natural
pain-killing machinery, preventing pain messages from reaching the brain.
Scientists are working toward the development of a morphine-like drug that will
have the pain-deadening qualities of morphine but without the drug's negative
side effects, such as sedation and the potential for addiction. Patients receiving morphine also face
the problem of morphine tolerance, meaning that over time they require higher
doses of the drug to achieve the same pain relief. Studies have identified
factors that contribute to the development of tolerance; continued progress in
this line of research should eventually allow patients to take lower doses of
morphine.
One objective of investigators working to develop the future generation of
pain medications is to take full advantage of the body's pain "switching
center" by formulating compounds that will prevent pain signals from being
amplified or stop them altogether. Blocking or interrupting pain signals,
especially when there is no injury or trauma to tissue, is an important goal in
the development of pain medications. An increased understanding of the basic
mechanisms of pain will have profound implications for the development of future
medicines. The following areas of research are bringing us closer to an ideal
pain drug.
Systems and Imaging: The
idea of mapping cognitive functions to precise areas
of the brain dates back to phrenology, the now archaic practice of studying
bumps on the head. Positron emission tomography (PET), functional magnetic
resonance imaging (fMRI), and other imaging technologies offer a vivid picture
of what is happening in the brain as it processes pain. Using imaging,
investigators can now see that pain activates at least three or four key areas
of the brain's cortex-the layer of tissue that covers the brain. Interestingly,
when patients undergo hypnosis so that the unpleasantness of a painful stimulus
is not experienced, activity in some, but not all, brain areas is reduced. This
emphasizes that the experience of pain involves a strong emotional component as
well as the sensory experience, namely the intensity of the stimulus.
Channels: The frontier in the search for new drug targets is represented by
channels. Channels are gate-like passages found along the membranes of cells
that allow electrically charged chemical particles called ions to pass into the
cells. Ion channels are important for transmitting signals through the nerve's
membrane. The possibility now exists for developing new classes of drugs,
including pain cocktails that would act at the site of channel activity.
Trophic Factors: A class of "rescuer" or "restorer" drugs
may emerge from our growing knowledge of trophic factors, natural chemical
substances found in the human body that affect the survival and function of
cells. Trophic factors also promote cell death, but little is known about how
something beneficial can become harmful. Investigators have observed that an
over-accumulation of certain trophic factors in the nerve cells of animals
results in heightened pain sensitivity, and that some receptors found on cells
respond to trophic factors and interact with each other. These receptors may
provide targets for new pain therapies.
Molecular Genetics: Certain
genetic mutations can change pain sensitivity and behavioral responses to pain.
People born genetically insensate to pain-that is, individuals who cannot feel
pain-have a mutation in part of a gene that plays a role in cell survival. Using
"knockout" animal models-animals genetically engineered to lack a certain
gene-scientists are able to visualize how mutations in genes cause animals to
become anxious, make noise, rear, freeze, or become hypervigilant. These genetic
mutations cause a disruption or alteration in the processing of pain information
as it leaves the spinal cord and travels to the brain. Knockout animals can be used to complement efforts
aimed at developing new drugs.
Plasticity: Following injury, the nervous system undergoes a tremendous
reorganization. This phenomenon is known as plasticity. For example, the spinal
cord is "rewired" following trauma as nerve cell axons make new
contacts, a phenomenon known as "sprouting." This in turn disrupts the
cells' supply of trophic factors. Scientists can now identify and study the
changes that occur during the processing of pain. For example, using a technique
called polymerase chain reaction,
abbreviated PCR, scientists can study the
genes that are induced by injury and persistent pain. There is evidence that the
proteins that are ultimately synthesized by these genes may be targets for new
therapies. The dramatic changes that occur with injury and persistent pain
underscore that chronic pain should be considered a disease of the nervous
system, not just prolonged acute pain or a symptom of an injury. Thus,
scientists hope that therapies directed at preventing the long-term changes that
occur in the nervous system will prevent the development of chronic pain
conditions.
Neurotransmitters: Just as mutations in genes may affect behavior, they may
also affect a number of neurotransmitters involved in the control of pain. Using
sophisticated imaging technologies, investigators can now visualize what is
happening chemically in the spinal cord. From this work, new therapies may
emerge, therapies that can help reduce or obliterate severe or chronic pain.
Hope for the future
Thousands of years ago, ancient
peoples attributed pain to spirits and treated it with mysticism and
incantations. Over the centuries, science has provided us with a remarkable ability to understand and control pain
with medications, surgery, and other treatments. Today, scientists understand a
great deal about the causes and mechanisms of pain, and research has produced
dramatic improvements in the diagnosis and treatment of a number of painful
disorders. For people who fight every day against the limitations imposed by
pain, the work of NINDS-supported scientists holds the promise of an even
greater understanding of pain in the coming years. Their research offers a
powerful weapon in the battle to prolong and improve the lives of people with
pain: hope.
Credits
Written by Stephanie E. Clipper, Office of Communications and Public Liaison,
NINDS
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