ATP responses in human C nociceptors

• Published in: Pain (Amsterdam) Vol. 98; no. 1; pp. 59 - 68
• Main Authors: Hilliges, Marita, Weidner, Christian, Schmelz, Martin, Schmidt, Roland, Ørstavik, Kristin, Torebjörk, Erik, Handwerker, Hermann
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.07.2002; Elsevier
• Subjects: Adenosine triphosphate; Adenosine Triphosphate - pharmacology; Adult; Biological and medical sciences; Dose-Response Relationship, Drug; Female; Fundamental and applied biological sciences. Psychology; Histamine - pharmacology; Hot Temperature; Human skin; Humans; Injections; Knee; Male; Nerve Fibers - drug effects; Nociceptors - drug effects; Osmolar Concentration; Pain; Pain - chemically induced; Pain Threshold - drug effects; Peripheral nerves; Physical Stimulation; Purinergic receptors; Reaction Time; Skin - innervation; Sodium Chloride - pharmacology; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; Vertebrates: nervous system and sense organs; Human skin; Pain; Purinergic receptors; Adenosine triphosphate; Peripheral nerves; Peripheral nervous system; Human; Nociception; Peripheral nerve; Peroneal nerve; Noxious stimulus; Discharge pattern; Electrophysiology; Thermal stimulus; Nerve fiber C; Nociceptor; Purinergic receptor; Skin; Sensitization; Mechanical stimulus; ATP
• ISSN: 0304-3959; 1872-6623
• DOI: 10.1016/S0304-3959(01)00469-9

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 iH 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 μl 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 iH 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.