Endothelin 1 activates and sensitizes human C-nociceptors.
Microneurography was used to record action potentials from afferent C-fibers in cutaneous fascicles of the peroneal nerve in healthy volunteers. Afferent fibers were classified according to their mechanical responsiveness to von Frey stimulation (75g) into mechano-responsive and mechano-insensitive nociceptors. Various concentrations of Endothelin1 (ET1) and Histamine were injected into the receptive fields of C-fibers. Activation and heat sensitization were monitored. Axon reflex flare and psychophysical ratings were assessed after injection of ET1 and codeine into the forearms after pre-treatment with an H1 blocker or sodium chloride. 65% of mechanosensitive nociceptors were activated by ET1. One-third showed long lasting responses (>15min). In contrast, none of thirteen mechano-insensitive fibers were activated. Sensitization to heat was observed in 62% of mechanosensitive and in 46% of mechano-insensitive fibers. Injection of ET1 produced a widespread axon reflex flare, which was suppressed by pre-treatment with an H1 receptor blocker. In addition, pain sensations were induced more often than itching by ET1 in contrast to codeine. No wheal was observed after injection of ET1. Both itching and pain were decreased after H1 blocker treatment. In summary: (1) In humans ET1 activates mechanosensitive, but not mechano-insensitive, nociceptors. (2) Histamine released from mast cells is not responsible for all effects of ET1 on C-nociceptors. (3) ET1 could have a differential role in pain compared to other chemical algogens which activate additionally or even predominantly mechano-insensitive fibers.
Namer
Barbara
B
Department of Physiology and Pathophysiology, University of Erlangen/Nürnberg, Germany Department of Sciences, SET, Halmstad University, Halmstad, Sweden Laboratory of Clinical Neurophysiology, Department of Neurology, Rikshospitalet University Hospital, Oslo, Norway Department of Clinical Neurophysiology, University Hospital, Uppsala, Sweden Department of Anesthesiology Mannheim, University Heidelberg, Germany.
Hilliges
Marita
M
Ørstavik
Kristin
K
Schmidt
Roland
R
Weidner
Christian
C
Torebjörk
Erik
E
Handwerker
Hermann
H
Schmelz
Martin
M
D004558:Electric Stimulation / Q000379:methods; D019332:Endothelin-1 / Q000008:administration & dosage / Q000502:physiology*; D006801:Humans; D036421:Nerve Fibers, Unmyelinated / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods / Q000523:psychology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology / Q000523:psychology; D012879:Skin Physiological Phenomena / Q000187:drug effects
D019332:Endothelin-1