Multiple chemical sensitivity: towards the end of controversy

Townsend Letter for Doctors and Patients, August-Sept, 2005 by Martin L. Pall

There are two types of puzzles surrounding the symptoms and signs of these illnesses. One is that they are very diverse, involving neuronal, neuroendocrine, circulatory, immune, biochemical and psychiatric properties. This has raised the question of how any understandable mechanism might be able to generate such a diverse group of symptoms and signs? A second puzzle is that these symptoms and signs are highly variable from one individual to another so both the pattern and the variability require satisfactory explanations. In my book (16) and elsewhere, (2) I have provided explanations for 16 different symptoms and signs that are found with reasonable frequency, based on one or more elements of the vicious cycle. It should be noted that these explanations are put forth as plausible mechanisms, not as established mechanisms. They include such things as orthostatic intolerance, possibly caused by nitric oxide effects both as a vasodilator and its effects on the sympathetic nervous system; sleep dysfunction such as nonrefreshing sleep, caused by elevated cytokines, by elevated nitric oxide and by elevated NF-kB activity; low NK cell activity, caused by oxidants and specifically by superoxide; fatigue which is found in all conditions with low energy metabolism may be caused by peroxynitrite mediated mitochondrial dysfunction. Even such psychiatric symptoms as anxiety (excessive NMDA activity in the amygdala) and depression (nitric oxide effects on the brain, locations still undetermined) may be explained by this mechanism.

[FIGURE 1 OMITTED]

The variability of the symptoms and signs may be explained by variation in tissue distribution of the underlying biochemistry. Nitric oxide, superoxide and peroxynitrite have limited diffusion in tissues (16) and the basic mechanisms outlined in the vicious cycle are cellular. It follows that one tissue may be impacted by this biochemistry whereas an adjacent tissue may be largely unaffected. The vicious cycle may propagate the tissue distribution into the future, thus producing a relatively stable pattern of symptoms and signs which varies from one patient to another. An example of this is that if the amygdala is impacted by this biochemistry, a patient will be expected to have symptoms of anxiety and possible panic attacks, but not otherwise. Similarly, if certain regions of the GI tract are impacted one may have irritable bowel syndrome (IBS) symptoms; note that IBS is reported to involve both excessive vanilloid activity and excessive nitric oxide.

Multiple Chemical Sensitivity (MCS)

Multiple chemical sensitivity is reported to be both the most common of these illnesses and has also been the most puzzling. It is characterized by exquisite chemical sensitivity to a wide variety of chemicals, with such sensitivity being apparently induced by previous chemical exposure. (4,5) There has not previously been an understanding as to how these chemicals act or how the exquisite sensitivity reported, on the order of 1000 times that of normals, can be generated. It has been clear, for some time however, that MCS is not caused by an IgE-based allergy or fundamentally by an immune response of any kind, but rather, involves neuronal dysfunction.