Neural sensitization model for multiple chemical sensitivity: Overview of theory and empirical evidence

Iris R. Bell, Carol M. Baldwin, Mercedes Fernandez, Gary E.R. Schwartz

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


This paper summarizes theory and evidence for a neural sensitization model of hyperresponsivity to low-level chemical exposures in multiple chemical sensitivity (M]CS). MCS is a chronic polysymptomatic condition in which patients report illness from low levels of many different, structurally unrelated environmental chemicals (chemical intolerance, CI). Neural sensitization is the progressive host amplification of a response over time from repeated, intermittent exposures to a stimulus. Drugs, chemicals, endogenous mediators, and exogenous stressors can all initiate sensitization and can exhibit cross-sensitization between different classes of stimuli. The properties of sensitization overlap much of the clinical phenomenology of MCS. Animal studies have demonstrated sensitization to toluene, formaldehyde, and certain pesticides, as well as cross-sensitization, e.g., formaldehyde and cocaine. Controlled human studies in persons with self-reported CI have shown heightened sensitizability in the laboratory to nonspecific experimental factors and to specific chemical exposures. Useful outcome measures include spectral electroencephalography, blood pressure, heart rate, and plasma beta-endorphin. Findings implicate, in part, dopaminergic mesolimbic pathways and limbic structures. A convergence of evidence suggests that persons with MCS or with low-level CI may share some characteristics with individuals genetically vulnerable to substance abuse: (a) elevated family histories of alcohol or drug problems; (b) heightened capacity for sensitization of autonomic variables in the laboratory; (c) increased amounts of electroencephalographic alpha activity at rest and under challenge conditions over time. Sensitization is compatible with other models for MCS as well. The neural sensitization model provides a direction for further systematic human and animal research on the physiological bases of MCS and CI.

Original languageEnglish (US)
Pages (from-to)295-304
Number of pages10
JournalToxicology and Industrial Health
Issue number4
StatePublished - Apr 1999


  • autonomic nervous system
  • chemical intolerance
  • electroencephalography
  • limbic system
  • mesolimbic
  • multiple chemical sensitivity
  • neural sensitization
  • substance abuse

ASJC Scopus subject areas

  • Toxicology
  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis


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