Chemical Sensitivity: Possible Reason Why People Get Sick When They Smell Odors

Background: Inflammatory conditions in the intestinal tract such as would occur from colitis (or LPS) may cause alterations in signaling by serotonin-producing enterochromaffin cells. A recent experiment shows serotonin mediates inflammatory cytokines and the immune system through the NF-kappaB pathway which can also regulate CYP transcription. (Zordofsky) These cells also contain TLR receptors and therefore ligands of TLR may excite these cells  and it has been suggested that TLR signaling stimulates neurohormones which have been shown to alter normal immune responses. Interestingly, this author also notes that IBS and enteritis increases the numbers of enteroendocrine cells but there is conflicting evidence on whether this is consistent in inflammatory disease. Admittedly, there is a lot to learn about how activation of these cells impact specific immune functions but identifies an important role  of bacteria  regulation in inflammation.(Bugonovic)

In addition, activation of TRP channels have been suggested as having a role in MCS. (Pall) Doihara shows that activation of these receptors may alter intestinal function and this is achieved through TRPV1 acting through a serotoninergic pathway. TRPV1 ligands can be produced endogenously and inflammatory processes within the intestinal tract may increase the production of these ligands that stimulate TRPV1 activation of enterochromaffin activity and serotonin secretion. (Nozawa) As Rhee explains, enterochromaffin cells provide the means for communication between the intestinal tract and the central nervous system. Disruption of these cells may also disrupt the interactions that exist between the microflora and the nervous system that may lead to altered responses in the nervous system. Also important is that regulation of immunity by enterochromaffin cells may be different depending on the T-cell environment which may be crucial to understanding alterations of immunity in environmental illness considering it has been proposed that many of the responses may have more of an autoimmune type presentation. (Motomura)

Many people with sensitivities to toxicants in the environment have pointed out that upon smelling an odor or upon exposure that they may feel sick or have "intestinal discomfort" that results in diarrhea or noticeable dysregulation of the intestinal tract.  A study that was published in 2007 helps to explain what might cause this condition. Serotonin is a hormone that assists in the regulation of the activities in the intestinal tract. Researchers have found that in the human intestinal tract serotonin and nasal olfactory receptors are expressed by enterochromaffin cells. Braun determined that serotonin is released when odorants in spices, fragrances, detergents and cosmetics are presented. The presentation of odorant ligands result in a calcium flux in the cell that results in this release. As the author notes, these chemicals that activate the odorant receptors may play an important role in vomiting, diarrhea and irritable bowel syndrome because the hormone serotonin controls modulation of the intestinal tract. Thus therapies that target the olfactory receptors may be useful in the treatment of gastrointestinal diseases and motility disorders. In addition, while the author does not mention this --- altered signaling by these receptors may be influential in conditions such as multiple chemical sensitivity and certain panic behaviors.

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Motomura, Y., Ghia, J. E., Wang, H., Akiho, H., El-Sharkawy, R. T., Collins, M., Wan, Y., Mclaughlin, J. T., and Khan, W. I. (2008). Enterochromaffin cell and 5-hydroxytryptamine responses to the same infectious agent differ in th1 and th2 dominant environments. Gut, 57(4):475-481. http://www.citeulike.org/user/HEIRS/article/3346104
Nozawa, K., Kawabata-Shoda, E., Doihara, H., Kojima, R., Okada, H., Mochizuki, S., Sano, Y., Inamura, K., Matsushime, H., Koizumi, T., Yokoyama, T., and Ito, H. (2009). Trpa1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells. Proceedings of the National Academy of Sciences of the United States of America, 106(9):3408-3413. http://www.citeulike.org/user/HEIRS/article/4184960#
Bogunovic, M., Dave, S. H., Tilstra, J. S., Chang, D. T. W., Harpaz, N., Xiong, H., Mayer, L. F., and Plevy, S. E. (2007). Enteroendocrine cells express functional toll-like receptors. Am J Physiol Gastrointest Liver Physiol, 292(6):G1770-1783. http://www.citeulike.org/user/HEIRS/article/6444698
 



Defining Multiple Chemical Sensitivity