Pain is not only a symptom, but also the cause of osteoarthritis
In fact, pain is a feeling of discomfort that the patient is aware of. The appearance of pain occurs due to the process of nociception – the transfer of information from, for example, a sick knee to the pain-processing centers of the spinal cord. Scientists at the University of Rochester (UK), working under the guidance of Dr. Stephanos Kyrkanides, have received convincing evidence that the two-way nociceptive "dialogue" of neurons initially ensures the transfer of inflammation from arthritic joints to the spinal cord, and then its spread to other joints.
Moreover, if joint arthritis causes inflammation of the nervous tissue, it can contribute to the development of diseases such as Alzheimer's disease and multiple sclerosis. The results of the work allowed the authors to identify potential therapeutic targets for the treatment of osteoarthritis that can affect key inflammatory receptors on sensitive nerve cells.
Osteoarthritis is the most common form of arthritis, accompanied by an acute pain symptom and leading to loss of cartilage and joint deformity.
Until recently, it was believed that the cause of osteoarthritis is exclusively age-related inevitable wear of cartilage. Not so long ago it became known that specific biochemical changes contribute to the development of the disease, and the authors proved for the first time that these changes are associated with the processing of pain impulses.
According to earlier studies, the sensitivity of specific nerve pathways along which pain impulses travel increases after each pulse. This may be partly due to an ancient survival mechanism (don't do what causes pain). In addition, pain is clearly associated with inflammation (swelling and fever).
It is known that the compounds involved in the development of inflammation cause a feeling of pain, and when they are administered, hypersensitivity to pain develops. The authors devoted their work to one of such pro–inflammatory chemical signals - interleukin-1-beta (IL-1?), which stimulates anti-infectious immunity. They created genetically modified mice, in whose jaw joint (often affected by arthritis) it is possible to increase the production of interleukin-1-beta at will. Experiments have shown that an increase in the level of interleukin-1-beta in the peripheral joint increases the level of this compound in certain regions of the spinal cord.
The results of work with the second, more complex, mouse model showed that an increase in the level of interleukin-1-beta in spinal cord astrocytes increases the symptoms of osteoarthritis in the joints. In earlier studies, it was established that astrocytes – one of the types of neuroglia cells that maintain the normal state of neurons in the spinal cord and brain – act as immune cells of the central nervous system. One of their functions is the release of cytokines, such as interleukin-1-beta, if necessary to combat a particular disease. The same cytokines are released by neurons of the joints, which may explain the "dialogue" of neurons transmitting pain symptoms, inflammation and hypersensitivity in both directions.
In both mouse models, experimental techniques blocking the interleukin-1-beta-mediated mechanism neutralized the effects of the described "dialogue". The authors used the IL-1RA molecule, which prevents the interaction of interleukin-1-beta with its receptor on nerve cells. Existing drugs, such as Kineret (anakinra) from Amgen, intended for the treatment of rheumatoid arthritis, similarly to IL-1RA block the ability of interleukin-1-beta to transmit a pain signal using specific nerve cell receptors. Currently, researchers are exploring the possibility of using such drugs to treat osteoarthritis.
The consequences of the revealed process are much broader than it seems at first glance. If 10 astrocytes secrete interleukin-1-beta in response to a painful impulse, this can affect about 1000 nearby cells, which significantly increases the area of inflammation. Astrocytes of the spinal cord are surrounded by sensitive nerves interacting with peripheral cells, which further enhances the effect. According to the model developed by the authors, inflammation enhanced by the central nervous system can send impulses to the joints, where inflammatory factors are released in response.
One of these factors is the calcitonin gene-associated peptide (calcitonin gene related peptide, CGRP). The authors observed an increase in the production of this compound in the primary sensitive fibers of the same regions in which the level of interleukin-1-beta increases. This fact indicates that the release of interleukin-1-beta by sensitive neurons can trigger the synthesis of CGRP in the joints. Previously, the authors demonstrated the ability of CGRP to stimulate premature maturation and death of chondrocytes, which is one of the main signs of osteoarthritis.
According to the authors, the results obtained confirm that joints can transmit inflammation in the form of increased levels of interleukin-1-beta to the spinal cord, which is enough to spread the disease to other joints. They believe that this process plays an important role in the formation of not only orthopedic, but also neurological diseases in which the mechanisms of inflammation are involved.
Portal "Eternal youth" http://vechnayamolodost.ru / based on ScienceDaily – Pain Is Not A Symptom Of Arthritis, Pain Causes Arthritis, Study Shows
02.10.2008