Testing the neural sensitization and kindling hypothesis for illness from low levels of environmental chemicals.

Abstract

Sensitization in the neuroscience and pharmacology literatures is defined as progressive increase in the size of a response over repeated presentations of a stimulus. Types of sensitization include stimulant drug-induced time-dependent sensitization (TDS), an animal model related to substance abuse, and limbic kindling, an animal model for temporal lobe epilepsy. Neural sensitization (primarily nonconvulsive or subconvulsive) to the adverse properties of substances has been hypothesized to underlie the initiation and subsequent elicitation of heightened sensitivity to low levels of environmental chemicals. A corollary of the sensitization model is that individuals with illness from low-level chemicals are among the more sensitizable members of the population. The Working Group on Sensitization and Kindling identified two primary goals for a research approach to this problem: to perform controlled experiments to determine whether or not sensitization to low-level chemical exposures occurs in multiple chemical sensitivity (MCS) patients; and to use animal preparations for kindling and TDS as nonhomologous models for the initiation and elicitation of MCS.

Methylmercury: A potential environmental risk factor contributing to epileptogenesis

“…However, chronic exposure to these factors may act as risk modifiers to alter the susceptibility and to accelerate the onset of a disease or disorder caused by other pathogens or genetic defects (for review, see Sorg and Prasad, 1997; Bell et al, 1997a, 1997b; Gilbert, 2001). In some cases, effects of early developmental environmental exposure may not be expressed until later in adult life (Vathy 2001; Landrigan et al, 2005; Doherty et al, 2009; Montandon et al, 2009; Fox et al, 2010).…”

Indoor Volatile Organic Compounds and Chemical Sensitivity Reactions

“…It has been hypothesized that MCS occurs from repeated exposure to low levels of chemicals, particularly VOCs; therefore, the olfactory system probably plays an important role in the initial expression of MCS symptoms [13, 14]. Olfactory stimulation probably represents the most likely route of exposure [15], and it is reasonable to assume that a significant activation of the olfactory epithelium (OE) cells can provide sufficient input into the CNS limbic circuits to induce sensitization. There may be a mechanism by which repeated olfactory stimulation and other sensitization processes induced by some other physiological process are exacerbated by prior, repeated olfactory stimulation.…”

Acquiring Symptoms in Response to Odors: A Learning Perspective on Multiple Chemical Sensitivity

“…Neural sensitization refers to an increasing intensity of responses to stimuli, such as drugs, as a result of repeated intermittent exposure. In MCS, it is hypothesized that olfactory, limbic, mesolimbic, and related pathways of the CNS are involved 34,35. Sensitization effects are more likely with stronger stimuli and in conditions of physical and psychological stress.…”

“…Neural sensitization has been contrasted with conditioning as a potential model for MCS 2,34,37. Both basic forms of learning are often distinguished as nonassociative (implying one stimulus) and associative learning (implying two stimuli becoming associated), respectively.…”