Substance P causes pain - but also heals

Article Abstract:

Substance P is one of the three neuropeptides in mammals, known as tachykinins, that transmit pain signals in the nervous system. Substance P is released from nerve cells and causes pain; it is present in the brain, skin, lungs, and intestines. This neuropeptide is involved in many diseases and disorders, such as arthritis, psoriasis, and asthma. Increases in the number of receptors for substance P are observed in inflamed joint tissue in patients with rheumatoid arthritis and in lung tissue of patients with asthma. Tissues near blood and lymph vessels in patients with Crohn's disease or ulcerative colitis also have large numbers of receptors for Substance P, while normal tissue contains very little, if any. Substance P makes cells more responsive to any stimuli, either those that produce pain or those that stop pain. Sensitivity to pain killers, such as the enkephalins and and the adenosine-mediated neurotransmitters, which are naturally produced by the body, is increased by this peptide. Substance P also has counteractive roles in the inflammatory response; it promotes inflammation by dilating blood vessels, allowing inflammatory immune cells to enter into the area, but also recruits cells that cause healing of the damage caused by inflammation. Substance P may be involved in the interaction between the immune system and the nervous system. In a certain type of nerve tissue known as astrocytes, which do not transmit nerve signals, the number of substance P receptors increases if the nervous tissue is damaged. This prevents the nervous tissue from regenerating. If substance P could be blocked, it is possible that the nervous tissue could regenerate after damage. Recent studies showed that if the steroid methylprednisolone is administered within eight hours after spinal cord injury, recovery rates from the injury are increased. It is possible that methylprednisolone blocks the substance P receptor. The receptor for substance P has been isolated and characterized. This allows the identification of substances that can inhibit substance P, and thus promote healing or lessen pain. (Consumer Summary produced by Reliance Medical Information, Inc.)

Research, Causes of, Pain, Inflammation, United States. National Institute of Mental Health, Substance P

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New transplant method evades immune attack

Article Abstract:

Insulin-dependent (type I) diabetes mellitus is a disease in which the patient's pancreatic islet cells, the cell type that manufactures insulin, degenerate. Functioning islet cells can be transplanted into the pancreas of a diabetic patient, and to prevent the body from rejecting the foreign tissue, immunosuppressant drugs must be given. Unfortunately, the drugs have significant side effects. A new approach, taken by a research group led by Ali Naji at the Hospital of the University of Pennsylvania, is to transplant islet cells into the thymus, the organ where T cells (important cells in immune system function) mature. The T cells, in effect, are 'taught' that the proteins which they encounter in the thymus, including those of the transplanted islet cells, are acceptable and should not be attacked. In experiments with rats, the animals' immune systems appeared to accept the foreign islet cells as 'self' and did not reject them. The T cell population at the time of transplantation was reduced by the addition of antibodies, to allow new T cells to mature. Application of Naji's results in human diabetes could be hindered by several factors, including the scarcity of islet cells: only 1,000 pancreases are available in the United States each year, and more than one is needed to supply enough islet cells for a transplantation. Animal donors, however, could be used if the procedure proves effective. Another problem may be the continued destruction of the patient's own islet cells. This involves a different subset of T cells from those that mediate transplant rejection. Preliminary results from Naji's group, though, suggest that this does not occur. The next research steps will be taken using larger animals (dogs or pigs). An important additional finding is that subsequent transplants into the recipient's kidney were not rejected. This implies that organ transplantation could begin with implantation of a small piece of foreign tissue, to prepare the immune system. The organ could then be transplanted, without the need for immunosuppressive drugs. (Consumer Summary produced by Reliance Medical Information, Inc.)

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Induction of donor-specific unresponsiveness by intrathymic islet transplantation

Article Abstract:

In insulin-dependent diabetes mellitus, the islet cells of the pancreas, which produce insulin, are destroyed. The disease can be treated by transplanting donated islet cells into the pancreas; however, such grafts are often rejected by the recipient's immune system, even when immunosuppressant drugs are given. Furthermore, these drugs have undesirable side effects. An alternative is transplantation of islet cells to an 'immunologically privileged' site (a part of the body where the immune system does not function). Sites traditionally considered immunologically privileged are the brain and the testicle; research results now indicate that the thymus (the organ where T cells mature) is another such site. Experiments were carried out in which islet cells were removed from rats and implanted into the thymus of recipient rats in which diabetes had been experimentally induced. Some recipients received an injection of antiserum to rat lymphocytes (ALS) to deplete their supply of T cells. Animals that received ALS underwent a depletion of their T cell population, and the new T cells that were formed received their immunological 'education' in an environment containing 'foreign' antigens. Thus, the 'self versus non-self' distinction, which is the basis for graft rejection, was no longer made when the foreign islet cells were implanted. Results showed that the islet cells implanted in the thymus survived successfully (reducing blood glucose to normal) for many days, and one graft survived indefinitely, whereas grafts transplanted to conventional transplant sites, such as the kidney or liver, were immediately rejected. Ten of 13 grafts implanted in rats that had received ALS survived permanently. When four rats with these permanent islet grafts underwent transplantation of new grafts into the kidney, rejection did not take place. Thus, the animals' immune systems had been altered by placement of the first graft into the thymus. The results suggest the possibility of preventing graft rejection without the use of immunosuppressant drugs. (Consumer Summary produced by Reliance Medical Information, Inc.)

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