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This chapter outlines the views about physical or natural responses from ancient Greek philosophers until the revolutionary medical theories that were introduced by Giorgio Baglivi and Francis Glisson. It studies Baglivi's claim that fibers composing the organs—particularly the muscles—are directly responsive to irritation. It shows that the Scientific Revolution that occurred during the Renaissance had deeply affected the understanding of living matter in a deep and very basic way: Organs were all composed of fibers, despite their differences in form and function. Gottfried Leibniz is credited as being the first one to have held this view.

A localized irritation of the skin, if sufficiently potent, produces a remarkable change in the quality of mechanically evoked sensations in a large area surrounding the injury. In the case of a particularly noxious stimulus—a burn, a cut, or crush—the skin becomes hyperalgesic: normally painful stimuli such as a pinprick elicit abnormally intense and prolonged sensations of pain (punctate hyperalgesia), and the threshold for pain may be lowered so that normally innocuous stimuli such as a light touch are painful. The unpleasant, abnormal sensory states (dysaesthesiae) of hyperalgesia and hyperknesis are qualitatively very different as illustrated by the different sensations and reactions in response to the same stimuli. In hyperalgesic skin, a prickly hair elicits pain as does light stroking with a cotton swab. In contrast, when the same stimuli are applied to hyperknesic skin, they evoke sensations of itch and reactions of scratching the stimulated area. The dysaesthesiae of hyperalgesia or hyperknesis when elicited within the area of cutaneous irritation are called ‘primary’. Those evoked by stimuli delivered outside this primary area are termed ‘secondary’. This chapter discusses the contributions of primary cutaneous peripheral nerve fibres to the cutaneous dysaesthesiae of secondary hyperalgesia and secondary hyperknesis.

Compared to other Fabians, Shaw relied heavily on attention given to his personality, his appearance, to his ideas, and, most importantly, his verbalizing. One of the fundamental aspects of Shaw's perspective was revealed when he told Beatrice Webb in 1925 that the need arises for new thought that would raise the awareness. Shaw attempted to further his intention to irritate as such measures would draw attention to relevant matters. Irritation, particularly scandalizing, frustrating, or shocking, was one of the common results of Shaw's actions since the unresolved ending of the permeative strategy could be associated with irritation. This chapter highlights the irritation at the beginning of compositions that would initiate or provoke the attention of listeners and readers.

Goethe's evaluation of Pompeii in the Italian Journey reflects the two emotions of irritation caused by this unique archaeological encounter with antiquity, and of excitement about the discovered artefacts. These are kept separate and divided into two narrative strands describing one and the same experience. This chapter traces how Goethe was able to overcome the initial irritation with Pompeii using three elements of Pompeian wall painting: ornament, polychromy, and the central figured panel. This development in his thought can be seen by contrasting the opposing descriptions in the Italian Journey with his examination of Pompeii in his essays on art and reviews of Wilhelm Ternite and Wilhelm Zahn's colour plates.