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
There are many causes of back pain. Pain in the low back can relate to the bony lumbar spine, discs between the vertebrae, ligaments around the spine and discs, spinal cord and nerves, muscles of the low back, internal organs of the pelvis and abdomen, and the skin covering the lumbar area.
A pinched nerve can be caused of a variety of conditions, for example, carpal tunnel syndrome, herniated disc, sciatica, arthritis, spinal stenosis, trauma, and more. Common symptoms of a pinched nerve include pain, numbness, tingling, and weakness. Treatment of a pinched nerve depends on the cause of the pinched nerve.
Rheumatoid arthritis is an autoimmune disease that causes chronic inflammation of the joints, the tissue around the joints, as well as other organs in the body. Because it can affect multiple other organs of the body, rheumatoid arthritis is referred to as a systemic illness and is sometimes called rheumatoid disease.
Gout is a condition that results from crystals of uric acid depositing in tissues of the body. Gout is a condition that can lead to abnormally elevated levels of uric acid in the
blood, recurring attacks of joint inflammation (arthritis), deposits of
hard lumps of uric acid in and around the joints, and decreased kidney
function and kidney stones.
Headaches can be divided into two categories: primary headaches and secondary headaches. Migraine headaches, tension headaches, and cluster headaches are considered primary headaches. Secondary headaches are caused by disease. Headache symptoms vary with the headache type. Over-the-counter pain relievers provide short-term relief for most headaches.
The knee joint is composed of three compartments and ligaments which stabilize the joint. Causes of knee pain may include injury, degeneration, infrequently infection and rarely bone tumors. Although routine x-rays do not revel meniscus tears, they can be used to exclude other problems of the bones and tissues. The knee joint is the most commonly involved joint in rheumatic disease, as well as immune diseases that affect various tissues of the body.
Crohn's disease is a chronic inflammatory disease,
primarily involving the small and large intestine, but which can
affect other parts of the digestive system as well. Abdominal pain, diarrhea, vomiting, fever, and weight loss are
common symptoms.
Menstrual cramps (pain in the belly and pelvic area) are experienced by women as a result of menses. Menstrual cramps are not the same as premenstrual syndrome (PMS). Menstrual cramps are common, and may be accompanied by headache, nausea, vomiting, constipation, or diarrhea. Severity of menstrual cramp pain varies from woman to woman. Treatment includes OTC or prescription pain relief medication.
Bursitis of the hip results when the fluid-filled sac (bursa) near the hip becomes inflamed due to localized soft tissue trauma or strain. Symptoms include stiffness and pain around the hip joint. If the hip bursa is not infected, hip bursitis can be treated with ice compresses, rest, and antiinflammatory and pain medications.
Fibromyalgia, formerly
known as fibrositis, causes chronic pain, stiffness, and
tenderness of muscles, tendons, and joints without detectable inflammation. Fibromyalgia patients have an unusually low pain threshold. Symptoms of fibromyalgia include fatigue, abnormal sleep, mental/emotional disturbances, abdominal pain, migraine and tension headaches, and irritable bladder. Treatment of fibromyalgia involves patient education, medication, exercise, and stress reduction.
Elbow pain is most often the result of tendinitis, which can affect the inner or outer elbow. Treatment includes ice, rest, and medication for inflammation. Inflammation, redness, warmth, swelling, tenderness, and decreased range of motion are other symptoms associated with elbow pain. Treatment for elbow pain depends upon the nature of the patient's underlying disease or condition.
Ankle pain is commonly due to a sprain or tendinitis. The severity of ankle sprains ranges from mild (which can resolve within 24 hours) to severe (which can require surgical repair). Tendinitis of the ankle can be caused by trauma or inflammation.
Neck pain (cervical pain) may be caused by any number of disorders and diseases. Tenderness is another symptom of neck pain. Though treatment for neck pain really depends upon the cause, treatment typically may involve heat/ice application, traction, physical therapy, cortisone injection, topical anesthetic creams, and muscle relaxants.
Osteoarthritis is a type of arthritis caused by inflammation, breakdown, and eventual loss of
cartilage in the joints. Also known as degenerative arthritis. Osteoarthritis
can be caused by aging, heredity, and injury from trauma or disease.
Sacroiliac joint (SI) dysfunction is a general term to reflect pain in the SI joints. Causes of SI joint pain include osteoarthritis, abnormal walking pattern, and disorders that can cause SI joint inflammation including gout, rheumatoid arthritis, psoriasis, and ankylosing spondylitis. Treatment includes oral medications, cortisone injections, and surgery.
Arthritis is inflammation of one or more joints. When joints are inflamed they can develop stiffness, warmth, swelling, redness and pain. There are over 100 types of
arthritis including osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, lupus, gout,
and pseudogout.
IBS (irritable bowel syndrome) is a common gastrointestinal disorder involving abnormal gut contractions (motility) characterized by abdominal pain,
bloating, mucous in stools, and irregular bowel habits with alternating diarrhea
and constipation, symptoms that tend to be chronic and to wax and wane over the
years. Treatment options include medication and lifestyle changes such as diet, exercise, and stress management to control symptoms. Also called spastic colitis, mucus colitis, nervous colon syndrome.
Psoriatic arthritis is a disease that causes skin and joint inflammation. Symptoms include painful, stiff, and swollen joints, tendinitis, and organ inflammation. Treatment involves antiinflammatory medications and exercise.
Cancer is a disease caused by an abnormal growth of cells, also called malignancy. It is a group of 100 different diseases, and is not contagious. Cancer can be treated through chemotherapy, a treatment of drugs that destroy cancer cells.
Bursitis of the knee results when any of the three fluid-filled sacs (bursae) become inflamed due to injury or strain. Symptoms include pain, swelling, warmth, tenderness, and redness. Treatment of knee bursitis depends on whether infection is involved. If the knee bursa is not infected, knee bursitis may be treated with ice compresses, rest, and antiinflammatory and pain medications.
Lumbar stenosis can be caused by degenerative arthritis (the most common cause), tumor, infection, or metabolic disorders (Paget's disease of the bone). Symptoms include low back pain, weakness, pain, numbness, and loss of sensation in the legs. Other conditions may cause similar symptoms of lumbar stenosis, including diabetic neuropathy, claudication, and peripheral vascular disease. Diagnosis, is a medical history and imaging studies. Lumbar stenosis may be treated with medication or surgery.
The inflammatory bowel diseases (IBD) are Crohn's disease (CD) and ulcerative colitis (UC). The intestinal complications of Crohn's disease and ulcerative colitis differ because of the characteristically dissimilar behaviors of the intestinal inflammation in these two diseases.
Chronic fatigue syndrome is a debilitating and complex disorder characterized by profound fatigue that lasts 6 months or longer, is not improved by bed rest, and may be worsened by physical or mental activity.
Drug addiction is a chronic disease that causes drug-seeking behavior and drug use despite negative consequences to the user and those around him. Though the initial decision to use drugs is voluntary, changes in the brain caused by repeated drug abuse can affect a person's self-control and ability to make the right decisions and increase the urge to take drugs. Drug abuse and addiction are preventable.
Degenerative disc disease makes the disc more susceptible to herniation (rupture) which can lead to localized or radiating pain. The pain from degenerative disc or joint disease of the spine is usually treated conservatively with intermittent heat, rest, rehabilitative exercises and medications to relieve pain, muscle spasm and inflammation.
A frozen shoulder (adhesive capsulitis) is when the shoulder joint experiences a significant loss in its range of motion due to inflammation, scarring, or injury. Treatment involves anti-inflammatory medication, cortisone injections, and physical therapy.
Neuropathic pain is chronic pain resulting from injury to the nervous system. The injury can be to the central nervous system (brain and spinal cord) or the peripheral nervous system (nerves outside the brain and spinal cord).
The five types of spondylolisthesis include 1) dysplastic, 2) isthmic, 3) degenerative, 4) traumatic, and 5) pathologic. The most common symptom of spondylolisthesis is lower back pain. Treatment depends on the type and severity of spondylolisthesis. Surgery is required in some cases of spondylolisthesis.
Pain management and treatment can be simple or complex, according to its cause. There are two basic types of pain, nociceptive pain and neuropathic pain. Some causes of neuropathic pain includes: complex regional pain syndrome, interstitial cystitis, and irritable bowel syndrome. There are a variety of methods to treat chronic pain, which are dependant on the type of pain experienced.
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