Brain, Vol. 124, No. 9, 1754-1764,
September 2001
© 2001 Oxford University Press
Roles of capsaicin-insensitive nociceptors in cutaneous pain and secondary hyperalgesia
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1 Institute of Physiology and Pathophysiology, Johannes Gutenberg University, Mainz, Germany, 2 Department of Neurosurgery and 3 Applied Physics Laboratory, Johns Hopkins University, USA
Correspondence to:
Rolf-Detlef Treede, Institute of Physiology and Pathophysiology, Johannes Gutenberg University, Saarstrasse 21, D-55099 Mainz, Germany E-mail: treede{at}mail.uni-mainz.de
Polymodal nociceptors respond to mechanical, thermal and chemical stimuli. Whereas sensitivities to heat and to the irritant substance capsaicin have recently been linked via the properties of the vanilloid receptor type 1 receptor ion channel, sensitivity to noxious mechanical stimuli such as the pinpricks used in clinical neurology seems to be unrelated. We investigated the peripheral neural basis of pinprick pain using quantitative psychophysical techniques combined with selective conduction block by nerve compression and selective desensitization by topical capsaicin treatment. Complete A-fibre block by compression of the superficial radial nerve (criterion: loss of first pain sensation) lowered the stimulus–response function for pinprick pain (–82 ± 6% versus baseline). Topical pretreatment of the skin with a 10% capsaicin cream also lowered the pinprick stimulus–response function (–32 ± 10%), whereas laser-evoked heat pain was eliminated completely (–96 ± 2%). Under combined capsaicin desensitization and A-fibre blockade, pinprick pain was eliminated completely (–98 ± 1%). Intradermal injection of 40 µg capsaicin into normal skin between two skin areas that had been pretreated with either capsaicin cream or vehicle produced secondary hyperalgesia with a 260% enhancement of the stimulus–response function for pinprick pain in both areas. In contrast, axon reflexive flare spread only into the vehicle-treated area. These results suggest that capsaicin-sensitive afferents, including polymodal A-fibre and C-fibre nociceptors, make a small contribution to pinprick pain and that capsaicin-insensitive C-fibres do not contribute significantly to either mechanical or heat pain. Pinprick pain is mediated primarily by capsaicin-insensitive A-fibre nociceptors, which include high-threshold mechanoreceptors and type I mechano-heat nociceptors. In addition, central sensitization to input from these A-fibre nociceptors is the primary mechanism that accounts for the enhanced pain in response to punctate mechanical stimuli in the zone of secondary hyperalgesia. These capsaicin-insensitive A-fibre nociceptors may also mediate hyperalgesia in neuropathic pain.
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