Intradermal histamine injection produces the Lewis triple response: a red spot, then a flush surrounding it, then a wheal. The spreading flare component is mediated by:
- A Direct histamine action on endothelial H1 receptors causing widespread vasodilation
- B Histamine-induced activation of the sympathetic vasodilator pathway
- C An axon reflex through sensory C-fibres releasing substance P and other neuropeptides ✓
- D Complement-derived C3a acting on dermal vessels
Correct answer: C. An axon reflex through sensory C-fibres releasing substance P and other neuropeptides
Explanation
Histamine directly dilates capillaries to produce the red spot and increases permeability to produce the wheal. The wider flare results from an axon reflex in sensory nerve endings: antidromic impulses travel along branching B-fibres, releasing substance P and calcitonin gene-related peptide, which vasodilate neighbouring vessels. This reflex arc explains why denervated skin shows the red spot and wheal but no flare. Sympathetic pathways and complement are not involved in the flare.
Reference: Ganong's Review of Medical Physiology, 26th ed.
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