 |
|
New study proves that pain is not a symptom of arthritis, pain causes arthritis
September 30, 2008New treatments will seek to interrupt 'crosstalk' between joints and the spinal cord
Pain is more than a symptom of osteoarthritis, it is an inherent and damaging part of the disease itself, according to a study published today in journal Arthritis and Rheumatism. More specifically, the study revealed that pain signals originating in arthritic joints, and the biochemical processing of those signals as they reach the spinal cord, worsen and expand arthritis. In addition, researchers found that nerve pathways carrying pain signals transfer inflammation from arthritic joints to the spine and back again, causing disease at both ends.
Technically, pain is a patient's conscious realization of discomfort. Before that can happen, however, information must be carried along nerve cell pathways from say an injured knee to the pain processing centers in dorsal horns of the spinal cord, a process called nociception. The current study provides strong evidence that two-way, nociceptive "crosstalk" may first enable joint arthritis to transmit inflammation into the spinal cord and brain, and then to spread through the central nervous system (CNS) from one joint to another.
Furthermore, if joint arthritis can cause neuro-inflammation, it could have a role in conditions like Alzheimer's disease, dementia and multiple sclerosis. Armed with the results, researchers have identified likely drug targets that could interfere with key inflammatory receptors on sensory nerve cells as a new way to treat osteoarthritis (OA), which destroys joint cartilage in 21 million Americans. The most common form of arthritis, OA eventually brings deformity and severe pain as patients loose the protective cushion between bones in weight-bearing joints like knees and hips.
"Until relatively recently, osteoarthritis was believed to be due solely to wear and tear, and inevitable part of aging," said Stephanos Kyrkanides, D.D.S., Ph.D., associate professor of Dentistry at the University of Rochester Medical Center. "Recent studies have revealed, however, that specific biochemical changes contribute to the disease, changes that might be reversed by precision-designed drugs. Our study provides the first solid proof that some of those changes are related to pain processing, and suggests the mechanisms behind the effect," said Kyrkanides, whose work on genetics in dentistry led to broader applications. The common ground between arthritis and dentistry: the jaw joint is a common site of arthritic pain.
Study Details
Past studies have shown that specific nerve pathways along which pain signals travel repeatedly become more sensitive to pain signals with each use. This may be a part of ancient survival skill (if that hurt once, don't do it again). Secondly, pain has long been associated with inflammation (swelling and fever).
In fact, past research has shown that the same chemicals that cause inflammation also cause the sensation of pain and hyper-sensitivity to pain if injected. Kyrkanides' work centers around one such pro-inflammatory, signaling chemical called Interleukin 1-beta (IL-1β), which helps to ramp up the bodies attack on an infection.
Specifically, Kyrkanides' team genetically engineered a mouse where they could turn up on command the production of IL-1β in the jaw joint, a common site of arthritis. Experiments showed for the first time that turning up IL-1β in a peripheral joint caused higher levels of IL-1β to be produced in the dorsal horns of the spinal cord as well.
Using a second, even more elaborately engineered mouse model, the team also demonstrated for the first time that creating higher levels of IL-1β in cells called astrocytes in the spinal cord caused more osteoarthritic symptoms in joints. Past studies had shown astrocytes, non-nerve cells (glia) in the central nervous system that provide support for the spinal cord and brain, also serve as the immune cells of CNS organs. Among other things, they release cytokines like IL-1β to fight disease when triggered. The same cytokines released from CNS glia may also be released from neurons in joints, possibly explaining how crosstalk carries pain, inflammation and hyper-sensitivity back and forth.
In both mouse models, experimental techniques that shut down IL-1β signaling reversed the crosstalk effects. Specifically, researchers used a molecule, IL-1RA, known to inhibit the ability of IL-1β to link up with its receptors on nerve cells. Existing drugs (e.g. Kineret® (anakinra), made by Amgen and indicated for rheumatoid arthritis) act like IL-1RA to block the ability IL-1β to send a pain signal through its specific nerve cell receptor, and Kyrkanides' group is exploring a new use for them as osteoarthritis treatment.
The implications of this process go further, however, because the cells surrounding sensory nerve cell pathways too can be affected by crosstalk. If 10 astrocytes secrete IL-1β in response to a pain impulse, Kyrkanides said, perhaps 1,000 adjacent cells will be affected, greatly expanding the field of inflammation. Spinal cord astrocytes are surrounded by sensory nerve cells that connect to other areas of the periphery, further expanding the effect. According to Kyrkanides' model, increased inflammation by in the central nervous system can then send signals back down the nerve pathways to the joints, causing the release of inflammatory factors there.
Among the proposed, inflammatory factors is calcitonin gene related peptide (CGRP). The team observed higher levels calcitonin-gene related peptide (CGRP) production in primary sensory fibers in the same regions where IL-1β levels rose, and the release of IL-1β by sensory neurons may cause the release of CGRP in joints. Past studies in Kyrkanides reveal that CGRP can also cause cartilage-producing cells (chondrocytes) to mature too quickly and die, a hallmark of osteoarthritis.
Joining Kyrkanides in the publication from the University of Rochester School of Medicine and Dentistry were co-authors M. Kerry O'Banion, M.D., Ph.D., Ross Tallents, D.D.S., J. Edward Puzas, Ph.D. and Sabine M. Brouxhon, M.D. Paolo Fiorentino was a student contributor and Jennie Miller was involved as Kyrkanides' technical associate. Maria Piancino, led a collaborative effort at the University of Torino, Italy. This work was supported in part by grants from the National Institutes of Health.
"Our study results confirm that joints can export inflammation in the form of higher IL-1β along sensory nerve pathways to the spinal cord, and that higher IL-1β inflammation in the spinal cord is sufficient in itself to create osteoarthritis in peripheral joints," Kyrkanides said. "We believe this to be a vitally important process contributing to orthopaedic and neurological diseases in which inflammation is a factor."
University of Rochester Medical Center
Furthermore, if joint arthritis can cause neuro-inflammation, it could have a role in conditions like Alzheimer's disease, dementia and multiple sclerosis. Armed with the results, researchers have identified likely drug targets that could interfere with key inflammatory receptors on sensory nerve cells as a new way to treat osteoarthritis (OA), which destroys joint cartilage in 21 million Americans. The most common form of arthritis, OA eventually brings deformity and severe pain as patients loose the protective cushion between bones in weight-bearing joints like knees and hips.
"Until relatively recently, osteoarthritis was believed to be due solely to wear and tear, and inevitable part of aging," said Stephanos Kyrkanides, D.D.S., Ph.D., associate professor of Dentistry at the University of Rochester Medical Center. "Recent studies have revealed, however, that specific biochemical changes contribute to the disease, changes that might be reversed by precision-designed drugs. Our study provides the first solid proof that some of those changes are related to pain processing, and suggests the mechanisms behind the effect," said Kyrkanides, whose work on genetics in dentistry led to broader applications. The common ground between arthritis and dentistry: the jaw joint is a common site of arthritic pain.
Study Details
Past studies have shown that specific nerve pathways along which pain signals travel repeatedly become more sensitive to pain signals with each use. This may be a part of ancient survival skill (if that hurt once, don't do it again). Secondly, pain has long been associated with inflammation (swelling and fever).
In fact, past research has shown that the same chemicals that cause inflammation also cause the sensation of pain and hyper-sensitivity to pain if injected. Kyrkanides' work centers around one such pro-inflammatory, signaling chemical called Interleukin 1-beta (IL-1β), which helps to ramp up the bodies attack on an infection.
Specifically, Kyrkanides' team genetically engineered a mouse where they could turn up on command the production of IL-1β in the jaw joint, a common site of arthritis. Experiments showed for the first time that turning up IL-1β in a peripheral joint caused higher levels of IL-1β to be produced in the dorsal horns of the spinal cord as well.
Using a second, even more elaborately engineered mouse model, the team also demonstrated for the first time that creating higher levels of IL-1β in cells called astrocytes in the spinal cord caused more osteoarthritic symptoms in joints. Past studies had shown astrocytes, non-nerve cells (glia) in the central nervous system that provide support for the spinal cord and brain, also serve as the immune cells of CNS organs. Among other things, they release cytokines like IL-1β to fight disease when triggered. The same cytokines released from CNS glia may also be released from neurons in joints, possibly explaining how crosstalk carries pain, inflammation and hyper-sensitivity back and forth.
In both mouse models, experimental techniques that shut down IL-1β signaling reversed the crosstalk effects. Specifically, researchers used a molecule, IL-1RA, known to inhibit the ability of IL-1β to link up with its receptors on nerve cells. Existing drugs (e.g. Kineret® (anakinra), made by Amgen and indicated for rheumatoid arthritis) act like IL-1RA to block the ability IL-1β to send a pain signal through its specific nerve cell receptor, and Kyrkanides' group is exploring a new use for them as osteoarthritis treatment.
The implications of this process go further, however, because the cells surrounding sensory nerve cell pathways too can be affected by crosstalk. If 10 astrocytes secrete IL-1β in response to a pain impulse, Kyrkanides said, perhaps 1,000 adjacent cells will be affected, greatly expanding the field of inflammation. Spinal cord astrocytes are surrounded by sensory nerve cells that connect to other areas of the periphery, further expanding the effect. According to Kyrkanides' model, increased inflammation by in the central nervous system can then send signals back down the nerve pathways to the joints, causing the release of inflammatory factors there.
Among the proposed, inflammatory factors is calcitonin gene related peptide (CGRP). The team observed higher levels calcitonin-gene related peptide (CGRP) production in primary sensory fibers in the same regions where IL-1β levels rose, and the release of IL-1β by sensory neurons may cause the release of CGRP in joints. Past studies in Kyrkanides reveal that CGRP can also cause cartilage-producing cells (chondrocytes) to mature too quickly and die, a hallmark of osteoarthritis.
Joining Kyrkanides in the publication from the University of Rochester School of Medicine and Dentistry were co-authors M. Kerry O'Banion, M.D., Ph.D., Ross Tallents, D.D.S., J. Edward Puzas, Ph.D. and Sabine M. Brouxhon, M.D. Paolo Fiorentino was a student contributor and Jennie Miller was involved as Kyrkanides' technical associate. Maria Piancino, led a collaborative effort at the University of Torino, Italy. This work was supported in part by grants from the National Institutes of Health.
"Our study results confirm that joints can export inflammation in the form of higher IL-1β along sensory nerve pathways to the spinal cord, and that higher IL-1β inflammation in the spinal cord is sufficient in itself to create osteoarthritis in peripheral joints," Kyrkanides said. "We believe this to be a vitally important process contributing to orthopaedic and neurological diseases in which inflammation is a factor."
University of Rochester Medical Center
Osteoarthritis Current Events and Osteoarthritis News RSSPine bark reduces inflammatory marker CRP in osteoarthritis
Osteoarthritis (OA), a type of arthritis caused by the breakdown and loss of cartilage, affects more than 20 million Americans.
MRI shows new types of injuries in young gymnasts
Adolescent gymnasts are developing a wide variety of arm, wrist and hand injuries that are beyond the scope of previously described gymnastic-related trauma, according to a study presented today at the annual meeting of the Radiological Society of North America (RSNA).
Adult stem cell breakthrough
The first tissue-engineered trachea (windpipe), utilising the patient's own stem cells, has been successfully transplanted into a young woman with a failing airway. The bioengineered trachea immediately provided the patient with a normally functioning airway, thereby saving her life.
First trachea transplant without immunosuppression
After 4 years of going from consultation to consultation, Claudia Castillo finally found a solution to her respiratory problems. The young Colombian woman suffered from a cough that took a long time to be diagnosed as tuberculosis.
Hip resurfacing is not for everyone
Hip resurfacing is often seen as a modern alternative to the more conventional total hip replacement, but new data from a study led by Rush University Medical Center suggest that a patient's age and gender are key to the operation's success.
New drug target in obesity: Fat cells make lots of melanin
As millions of Americans gear up for the Thanksgiving holiday, a new research report published online in The FASEB Journal, may provide some relief for those leery of having a second helping.
Elderly fare better when included in decisions on treatment trade-offs
Halting a medication that treats one ailment because it may worsen another is a treatment trade-off decision that elderly patients with multiple medical conditions would rather take part in, researchers at Yale School of Medicine report in a study published in the Journal of the American Geriatrics Society.
First international guidelines for treatment of psoriatic arthritis
Rheumatologists, dermatologists, and patient advocates have come together to publish the first-ever international guidelines for the treatment of psoriatic arthritis, a disease that mainly affects people who have psoriasis but also some people without it.
Nerve stimulation therapy alleviates pain for chronic headache
A novel therapy using a miniature nerve stimulator instead of medication for the treatment of profoundly disabling headache disorders improved the experience of pain by 80-95 percent, according to a new study from the University of California, San Francisco and the National Hospital for Neurology and Neurosurgery in London.
Incorporating Education in Exercise Programs Increases Benefits for Arthritis Patients, MU Researchers Find
Arthritis is the nation's most common cause of disability. The number of adults with doctor-diagnosed arthritis is projected to increase to 67 million by 2030, and a large proportion of U.S. adults will limit their activity as a result.
More Osteoarthritis Current Events and Osteoarthritis News Articles
 | Water Exercises for Osteoarthritis: The Effective Way to Reduce Pain and Stiffness, While Increasing Endurance and Strength by Ann A. Rosenstein Water Exercises for Osteoarthritis contains over 100 individual exercises and examples of exercise routines. It is richly illustrated with over 500 pictures so the reader can see all of the elements that go into an exercise program: equipment, warm-ups, stretching, aerobic exercises, strength exercises, balance exercises, exercises focusing on the abdominals, neck exercises, and cool downs.... |
 | The Arthritis Handbook: Improve Your Health and Manage the Pain of Osteoarthritis (A DiaMedica Guide to Optimum Wellness) by Grant Cooper According to conventional wisdom, arthritis pain is an inevitable part of aging. Not so, says Dr. Grant Cooper in this practical, accessible guide. For those who do develop osteoarthritic conditions, this book offers a blend of commonsense advice, dietary info, targeted exercise, and tips on useful supplements. According to the author, sufferers can often entirely avoid the use of medication,... |
 | The Arthritis Cure, Revised and Updated: The Medical Miracle That Can Halt, Reverse, And May Even Cure Osteoarthritis by Jason Theodosakis, Sheila Buff, Barry Fox Since its original publication in 1996, The Arthritis Cure has swept the nation, providing amazing relief for the millions who suffer chronic arthritis pain. By outlining a nine-point program that includes a new effective supplement, ASU, The Arthritis Cure Revised Edition describes a program that can halt, reverse, and possibly even cure degenerative osteoarthritis.Based on the most recent and... |
 | Osteoarthritis: Diagnosis and Medical/Surgical Management Written by the foremost experts, this text is a comprehensive clinical reference on osteoarthritis. Chapters review current information on the epidemiology, etiopathogenesis, and pathology of osteoarthritis, the biochemistry and molecular and cell biology of articular cartilage, and experimental models of osteoarthritis. Major sections focus on clinical presentations, roentgenologic and... |
 | Osteoarthritis: Preventing and Healing Without Drugs by Peter Bales Osteoarthritis affects over 20 million Americans and is the most common degenerative disorder in the United States. It causes more disability than any other degenerative disease and is occurring in epidemic proportions throughout the world. In this novel approach to understanding and treating osteoarthritis, orthopaedic surgeon Peter Bales highlights the nutritional connection to this painful and... |
 | Stop Osteoarthritis Now: Halting the Baby Boomers' Disease by Harris H. Mcilwain, Debra Fulgham Bruce What exactly is this debilitating disease? It is an inflammation in or around the joints caused by wear and tear on the cartilage and bone, resulting in pain, swelling, or stiffness in the back, knees, hips, hands, or other joints. The good news is that osteoarthritis can be successfully treated and may even be delayed or prevented. In Stop Osteoarthritis Now! Dr. Harris H. McIlwain provides the... |
 | Osteoarthritis (Natural Health Guide) by Zoltan Rona |
 | Osteoarthritis (The Facts) by Nigel K Arden, Elizabeth Arden, David Hunter Osteoarthritis is a common disorder of the joints that affects more than 2 million people in the UK, and studies suggest that this number will double in the next 20 years. The condition is strongly associated with ageing and is believed to affect up to 30% of people over 60 years of age. There are a number of misconceptions surrounding osteoarthritis and this, combined with the lack of effective... |
 | The Arthritis Foundation's Guide to Good Living with Osteoarthritis, 2nd Edition by Dorothy Foltz-Gray The Arthritis Foundation's Guide to Good Living With Osteoarthritis provides clear, understandable information on drugs, surgery, do-it-yourself treatments, exercise, alternative therapies and more to beat the pain of... |
| Diagnosis and Nonsurgical Management of Osteoarthritis by Kenneth D. Brandt Pathogenesis of OA, common diagnostic pitfalls, case presentations, synovial fluid analysis, joint imaging, joint protection, and nonmedicinal therapy are reviewed. Recommendations for systemic and local pharmacologic therapy are presented, along with a rational strategy for therapy of OA pain. A section of the book is devoted to pharmacologic modifications of tissue damage of... |
| © 2009 BrightSurf.com |