Substance P Neuromodulation Through Volume Transmission

Aberrant central nervous system mechanisms with modulation of peripheral input has been proposed as an explanation for the multiple symptoms of the fibromyalgia syndrome. Pain and stress appear to be involved in the pathophysiology of this disease. Substance P may participate in that it is a major contributor to pain transmission and acts in both the central and peripheral parts of the nervous system. In this paper, a possible explanation for some features of the fibromyalgia syndrome is given considering the functional interaction of substance P and the concept of volume transmission. Volume transmission is the concept of parasynaptic, as opposed to synaptic, communication. It is the idea that informational substances acting in the parasynaptic mode are likely to be released at points remote from the target cells and reach the cells by diffusion through extracellular fluid. Based on evidence already published and my own experiments, I hypothesize that modulation of pain and stress is primarily by inte-grative neurosecretion. The inflammatory and immune responses regulated by substance P are very important parts of this modulation process. The process can more easily be explained when we look at substance P, extracellular communication, and volume transmission. The fibromyalgia syndrome appears when this modulation process cannot adjust to immunological and inflammatory defense processes.