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his paper outlines the primary factors that affect the neural mediation of behavioral responses to chemical irritants. First, effective irritants must permeate the cornified epithelium or penetrate the mucosa to gain access to nociceptive nerve endings that are present in the skin or mucosa. Physicochemical properties of the irritant/repellent will determine the degree to which an effective concentration can be attained at the nerve endings. Second, endings of specific classes of somatosensory neurons are present in the periphery that, when appropriately stimulated by chemical as well as thermal or mechanical means, signal potential or actual tissue damage by causing pain or sensory irritation. Finally, secondary processes (sensitization, desensitization, and plasma leakage [extravasation]) that modulate the peripheral neural response to potential irritants are discussed.