Multiple chemical sensitivity: It's time to catch up to the science.

Multiple chemical sensitivity (MCS) is a complex medical condition associated with low dose chemical exposures. MCS is characterized by diverse features and common comorbidities, including fibromyalgia, cough hypersensitivity, asthma, and migraine, and stress/anxiety, with which the syndrome shares numerous neurobiological processes and altered functioning within diverse brain regions. Predictive factors linked to MCS comprise genetic influences, gene-environment interactions, oxidative stress, systemic inflammation, cell dysfunction, and psychosocial influences. The development of MCS may be attributed to the sensitization of transient receptor potential (TRP) receptors, notably TRPV1 and TRPA1. Capsaicin inhalation challenge studies demonstrated that TRPV1 sensitization is manifested in MCS, and functional brain imaging studies revealed that TRPV1 and TRPA1 agonists promote brain-region specific neuronal variations. Unfortunately, MCS has often been inappropriately viewed as stemming exclusively from psychological disturbances, which has fostered patients being stigmatized and ostracized, and often being denied accommodation for their disability. Evidence-based education is essential to provide appropriate support and advocacy. Greater recognition of receptor-mediated biological mechanisms should be incorporated in laws, and regulation of environmental exposures.

Neurological susceptibility to environmental exposures: pathophysiological mechanisms in neurodegeneration and multiple chemical sensitivity.

The World Health Organization lists air pollution as one of the top five risks for developing chronic non-communicable disease, joining tobacco use, harmful use of alcohol, unhealthy diets and physical inactivity. This review focuses on how host defense mechanisms against adverse airborne exposures relate to the probable interacting and overlapping pathophysiological features of neurodegeneration and multiple chemical sensitivity. Significant long-term airborne exposures can contribute to oxidative stress, systemic inflammation, transient receptor subfamily vanilloid 1 (TRPV1) and subfamily ankyrin 1 (TRPA1) upregulation and sensitization, with impacts on olfactory and trigeminal nerve function, and eventual loss of brain mass. The potential for neurologic dysfunction, including decreased cognition, chronic pain and central sensitization related to airborne contaminants, can be magnified by genetic polymorphisms that result in less effective detoxification. Onset of neurodegenerative disorders is subtle, with early loss of brain mass and loss of sense of smell. Onset of MCS may be gradual following long-term low dose airborne exposures, or acute following a recognizable exposure. Upregulation of chemosensitive TRPV1 and TRPA1 polymodal receptors has been observed in patients with neurodegeneration, and chemically sensitive individuals with asthma, migraine and MCS. In people with chemical sensitivity, these receptors are also sensitized, which is defined as a reduction in the threshold and an increase in the magnitude of a response to noxious stimulation. There is likely damage to the olfactory system in neurodegeneration and trigeminal nerve hypersensitivity in MCS, with different effects on olfactory processing. The associations of low vitamin D levels and protein kinase activity seen in neurodegeneration have not been studied in MCS. Table 2 presents a summary of neurodegeneration and MCS, comparing 16 distinctive genetic, pathophysiological and clinical features associated with air pollution exposures. There is significant overlap, suggesting potential comorbidity. Canadian Health Measures Survey data indicates an overlap between neurodegeneration and MCS (p < 0.05) that suggests comorbidity, but the extent of increased susceptibility to the other condition is not established. Nevertheless, the pathways to the development of these conditions likely involve TRPV1 and TRPA1 receptors, and so it is hypothesized that manifestation of neurodegeneration and/or MCS and possibly why there is divergence may be influenced by polymorphisms of these receptors, among other factors.