ATP responses in human C nociceptors.
Microelectrode recordings of impulse activity in nociceptive C fibres were performed in cutaneous fascicles of the peroneal nerve at the knee level in healthy human subjects. Mechano-heat responsive C units (CMH), mechano-insensitive but heat-responsive (CH) as well as mechano-insensitive and heat-insensitive C units (CM(i)H(i)) were identified. A subgroup of the mechano-insensitive units was readily activated by histamine. We studied the responsiveness of these nociceptor classes to injection of 20 microl 5 mM adenosintriphosphate (ATP) using saline injections as control. Because of mechanical distension during injection, which typically activates mechano-responsive C fibres, interest was focused on responsiveness to ATP after withdrawal of the injection needle. Post-injection responses were observed in 17/27 (63%) mechano-responsive units and in 14/22 (64%) mechano-insensitive units. Excitation by ATP occurred in 9/11 CH units and in 5/11 CM(i)H(i) units. ATP responsive units were found both within the histamine-responsive and the histamine-insensitive group of mechano-insensitive fibres. ATP responses appeared with a delay of 0-180 s after completion of injection; responses were most pronounced during the first 1-3 min of activation, and irregular ongoing activity was observed for up to 10 or even 20 min. ATP responses were dose-dependent, concentrations lower than 5 mM gave weaker responses. No heat or mechanical sensitisation was observed in any of the major fibre classes. In conclusion, we have shown that ATP injections at high concentrations activate C-nociceptors in healthy human skin, without preference for mechano-responsive or mechano-insensitive units. ATP did not sensitise human C fibres for mechanical or heat stimuli. We discuss how various mechanisms might contribute to the observed responses to ATP.
Hilliges
Marita
M
Department of Clinical Neurophysiology, University of Uppsala, S-75185 Uppsala, Sweden. marita.hilliges@ofa.ki.se
Weidner
Christian
C
Schmelz
Martin
M
Schmidt
Roland
R
Ørstavik
Kristin
K
Torebjörk
Erik
E
Handwerker
Hermann
H
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006358:Hot Temperature; D006801:Humans; D007267:Injections; D007717:Knee; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects*; D009619:Nociceptors / Q000187:drug effects*; D009994:Osmolar Concentration; D010146:Pain / Q000139:chemically induced; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D011930:Reaction Time; D012867:Skin / Q000294:innervation; D012965:Sodium Chloride / Q000494:pharmacology
D012965:Sodium Chloride; D006632:Histamine; D000255:Adenosine Triphosphate