• Jörn Schattschneider, Insa Zum Buttel, Andreas Binder, Gunnar Wasner, Jürgen Hedderich, and Ralf Baron.
• Sektion Neurologische Schmerzforschung und -therapie, Klinik für Neurologie des Universitätsklinikums Schleswig-Holstein, Campus Kiel, Schittenhelmstr 10, 24103, Kiel, Germany.
• Eur J Pain. 2007 Oct 1;11(7):756-63.

UnlabelledIt is well known that iontophoresis of norepinephrine in capsaicin treated skin is followed by an increase in thermal hyperalgesia. It is unclear if this action on nocicepitive afferents involves the release of prostaglandins. The aim of the present study was to determine: (1) the effect of norepinephrine iontophoresis on spontaneous and evoked pain in the human skin after topical application of capsaicin; (2) the effect of cyclooxygenase (COX) inhibition on changes in pain perception induced by norepinephrine application.MethodsTen volunteers were included in the study. Iontophoresis of norepinephrine or saline was performed in a randomized cross over design on the volar aspect of the forearm after topical application of capsaicin. In the second part of the study single iv. injections of saline or acetylsalicylic acid were performed in a randomized double blind cross over design. After the injection norepinephrine iontophoresis was performed on the skin treated with topical capsaicin. Spontaneous pain, mechanical hyperalgesia as well as warm and heat pain thresholds were measured before and after each iontophoresis.ResultsNorepinephrine did enhance spontaneous pain and mechanical and thermal hyperalgesia in capsaicin treated skin. Inhibition of COX I and II had no effect on the norepinephrine induced changes in pain perception.ConclusionThe results do not support the assumption that in human skin sensitized by topical capsaicin application of norepinephrine acts on nociceptive afferents via the release of prostaglandins. Thus, a direct action of norepinephrine on adrenergic receptors in the membrane of the afferent fibers is most likely.

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