Individual differences in neural sensitization and the role of context in illness from low-level environmental chemical exposures.

This paper summarizes the clinical phenomenology of multiple chemical sensitivity (MCS), outlines the concepts and evidence for the olfactory-limbic, neural sensitization model for MCS, and discusses experimental design implications of the model for exposure-related research. Neural sensitization is the progressive amplification of responsivity by the passage of time between repeated, intermittent exposures. Initiation of sensitization may require single toxic or multiple subtoxic exposures, but subsequent elicitation of sensitized responses can involve low or nontoxic levels. Thus, neural sensitization could account for the ability of low levels of environmental chemicals to elicit clinically severe, adverse reactions in MCS. Different forms of sensitization include limbic kindling of seizures (compare temporal lobe epilepsy and simple partial seizures) and time-dependent sensitization of behavioral, neurochemical, immunological, and endocrinological variables. Sensitized dysfunction of the limbic and mesolimbic systems could account in part for many of the cognitive, affective, and somatic symptoms in MCS. Derealization (an alteration in perception making familiar objects or people seem unfamiliar or unreal) is a common MCS symptom and has been linked with limbic dysfunction in clinical neuroscience research. Sensitization is distinct from, but interactive with, other neurobiological learning and memory processes such as conditioning and habituation (compare adaptation or tolerance). In previous studies, hypotheses for MCS involving sensitization, conditioning, and habituation (adaptation) have often been considered in isolation from one another. To design more appropriate chemical exposure studies, it may be important to integrate the various theoretical models and empirical approaches to MCS with the larger scientific literature on individual differences in these potentially interactive phenomena.