Neurogenic inflammation: Role of substance P

Abstract

The term “neurogenic inflammation” was introduced some 50 year, ago by a Hungarian group of Jancso and Szolcsanyi. In their initial experiments skin injection of an extract from chili pepper (capsaicin) resulted in local inflammation. It was suggested that capsaicin caused sensory nerves to release substance(s) which in turn activated inflammatory cells. The neuropeptide, substance P (SP) seems to be a prime candidate for these effects. All classical signs of inflammation (heat, redness, swelling, pain and consequent loss of function) may be affected by SP. Later, it became evident that many other neuropeptides including remaining tachykinins, vasoactive intestinal peptide, somatostatin, neuropeptide Y or bradykinins could also effect various functions of inflammation. However, for the purpose of this presentation we will concentrate on SP. Substance P affects inflammation both in a direct and indirect way. Directly, SP affects smooth muscle contraction, epithelial permeability, and neutrophile and macrophages traffic. In addition SP affects immune cells by activating mast cells, monocytes or lymphocytes to release their mediators such as histamine, IL-1, IL-2 and immunoglobulins respectively. Indirectly, these mediators are released from inflammatory cells and in turn activate additional surrounding cells to further propagate the inflammatory process. Similarly, pain perception associated with inflammation is in many systems mediated by a SP. Therefore, SP has been identified as a pro-inflammatory neuropeptide. Increased levels of SP have been found in many inflammatory diseases such as asthma, inflammatory bowel disease, rheumatoid, arthritis, nephritis, parasitic infections or various skin disorders. In fact it is safe to conclude that in all chronic and acute inflammatory conditions increased levels of SP are present. Moreover, it is possible by blocking SP release or SP receptors to interfere with the progress of inflammation. Obviously, this is a very complicated system in which various neuropeptides differentially interact and affect inflammatory cells. It is also clear that inflammation remains under strict neuronal control. We are only starting now to understand these interactions. Further investigations of the nerve/immune cell network could lead to new therapeutic strategies in management of inflammatory disease. Indeed, some agents which act upon SP, have been recently successfully included in clinical trials.