Mechanisms of adrenosensitivity in capsaicin induced hyperalgesia.
It 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.


METHODS
Ten 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.


RESULTS
Norepinephrine 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.


CONCLUSIONS
The 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.
Schattschneider
Jörn
J
Sektion Neurologische Schmerzforschung und -therapie, Klinik für Neurologie des Universitätsklinikums Schleswig-Holstein, Campus Kiel, Schittenhelmstr 10, 24103, Kiel, Germany.
Zum Buttel
Insa
I
Binder
Andreas
A
Wasner
Gunnar
G
Hedderich
Jürgen
J
Baron
Ralf
R
D000109:Acetylcholine / Q000008:administration & dosage; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage; D000328:Adult; D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D001241:Aspirin / Q000008:administration & dosage; D002211:Capsaicin; D018678:Cholinergic Agents / Q000008:administration & dosage; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D007478:Iontophoresis; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects*; D009638:Norepinephrine / Q000008:administration & dosage; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D011453:Prostaglandins / Q000378:metabolism; D012965:Sodium Chloride; D014664:Vasodilation / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018678:Cholinergic Agents; D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D012965:Sodium Chloride; D000109:Acetylcholine; D001241:Aspirin; D002211:Capsaicin; D009638:Norepinephrine; D007213:Indomethacin