Sensory responses to injection and punctate application of capsaicin and histamine to the skin

Pain. 2011 Nov;152(11):2485-2494. doi: 10.1016/j.pain.2011.06.001. Epub 2011 Jul 29.


A punctate, cutaneous application of capsaicin or histamine by means of a cowhage spicule elicits itch accompanied by pricking/stinging, burning, and typically, one or more areas of dysesthesia (alloknesis, hyperalgesia, hyperknesis). When applied over a wider and deeper area of skin by means of intradermal injection, histamine evokes the same sensory effects, but capsaicin evokes pain and hyperalgesia with allodynia instead of alloknesis. To examine the sensory effects of the spatial spread, depth, and amount of capsaicin and histamine, we applied different amounts of capsaicin or histamine by intradermal injection or by single vs multiple spicules within a circular cutaneous region of ~5 mm. Subjects rated the perceived intensity of itch, pricking/stinging, and burning for 20 minutes. Histamine injections or multiple spicules of capsaicin or histamine that resulted in a greater area of flare than a single spicule of each chemical evoked no greater magnitudes of sensation or areas of dysesthesia. Capsaicin injections elicited a dose-dependent increase in the magnitude of nociceptive sensations, areas of dysesthesia, and flare. However, there was little or no itch; and allodynia replaced alloknesis. Yet, hyperalgesia was typically accompanied by hyperknesis. We conclude that the pruritic sensory responses produced by capsaicin/histamine spicules and histamine injections may be due to activation of common nerve fibers, possibly different from those mediating the flare, and that capsaicin injections may activate additional fibers whose effects mask the sensory effects of fibers mediating itch and alloknesis but not hyperknesis.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Pain / chemically induced*
  • Acute Pain / physiopathology
  • Capsaicin / administration & dosage
  • Capsaicin / adverse effects*
  • Female
  • Histamine / administration & dosage
  • Histamine / adverse effects*
  • Histamine Agonists / administration & dosage
  • Histamine Agonists / adverse effects
  • Humans
  • Hyperalgesia / chemically induced*
  • Hyperalgesia / physiopathology
  • Injections, Intradermal / instrumentation
  • Injections, Intradermal / methods
  • Male
  • Nociceptors / drug effects
  • Nociceptors / physiology
  • Sensory System Agents / administration & dosage
  • Sensory System Agents / adverse effects
  • Skin / drug effects
  • Skin / innervation*


  • Histamine Agonists
  • Sensory System Agents
  • Histamine
  • Capsaicin