Brain, Vol. 122, No. 12, 2245-2257,
December 1999
© 1999 Oxford University Press
Review article |
Secondary hyperalgesia to punctate mechanical stimuli
Central sensitization to A-fibre nociceptor input
1 Institute of Physiology and Pathophysiology,Johannes Gutenberg University, Mainz, Germany and 2 Department of Neurosurgery, Johns Hopkins University, Baltimore, USA
Correspondence to:
Professor Dr med 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
Tissue injury induces enhanced pain sensation to light touch and punctate stimuli in adjacent, uninjured skin (secondary hyperalgesia). Whereas hyperalgesia to light touch (allodynia) is mediated by A-fibre low-threshold mechanoreceptors, hyperalgesia to punctate stimuli may be mediated by A- or C-fibre nociceptors. To disclose the relative contributions of A- and C-fibres to the hyperalgesia to punctate stimuli, the superficial radial nerve was blocked by pressure at the wrist in nine healthy subjects. Secondary hyperalgesia was induced by intradermal injection of 40 µg capsaicin, and pain sensitivity in adjacent skin was tested with 200 µm diameter probes (35–407 mN). The progress of conduction blockade was monitored by touch, cold, warm and first pain detection and by compound sensory nerve action potential. When A-fibre conduction was blocked completely but C-fibre conduction was fully intact, pricking pain to punctate stimuli was reduced by 75%, but burning pain to capsaicin injection remained unchanged. In normal skin without A-fibre blockade, pain ratings to the punctate probes increased significantly by a factor of two after adjacent capsaicin injection. In contrast, pain ratings to the punctate probes were not increased after capsaicin injection when A-fibre conduction was selectively blocked. However, hyperalgesia to punctate stimuli was detectable immediately after block release, when A-fibre conduction returned to normal. In conclusion, the pricking pain to punctate stimuli is predominantly mediated by A-fibre nociceptors. In secondary hyperalgesia, this pathway is heterosynaptically facilitated by conditioning C-fibre input. Thus, secondary hyperalgesia to punctate stimuli is induced by nociceptive C-fibre discharge but mediated by nociceptive A-fibres.
capsaicin; A-fibre nociceptors; C-fibre nociceptors; nerve conduction block; secondary hyperalgesia; neuropathic pain
AMH = A-mechanoheat nociceptors; HTM = high-threshold mechanoreceptors; LTM = low-threshold mechanoreceptors; LSD = least squares differences; SNAP = sensory nerve action potential
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  P. Schwenkreis, C. Maier, and M. Tegenthoff Functional Imaging of Central Nervous System Involvement in Complex Regional Pain Syndrome AJNR Am. J. Neuroradiol., August 1, 2009; 30(7): 1279 - 1284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Seifert, G. Kiefer, R. DeCol, M. Schmelz, and C. Maihofner Differential endogenous pain modulation in complex-regional pain syndrome Brain, March 1, 2009; 132(3): 788 - 800. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Lee, L. Zambreanu, D. K. Menon, and I. Tracey Identifying Brain Activity Specifically Related to the Maintenance and Perceptual Consequence of Central Sensitization in Humans J. Neurosci., November 5, 2008; 28(45): 11642 - 11649. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Hansen, T. Klein, W. Magerl, and R.-D. Treede Psychophysical Evidence for Long-Term Potentiation of C-Fiber and A{delta}-Fiber Pathways in Humans by Analysis of Pain Descriptors J Neurophysiol, March 1, 2007; 97(3): 2559 - 2563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Orstavik, I. Norheim, and E. Jorum Pain and small-fiber neuropathy in patients with hypothyroidism. Neurology, September 12, 2006; 67(5): 786 - 791. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Maihofner, H. O. Handwerker, and F. Birklein Functional imaging of allodynia in complex regional pain syndrome Neurology, March 14, 2006; 66(5): 711 - 717. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sycha, D. Samal, B. Chizh, S. Lehr, B. Gustorff, P. Schnider, and E. Auff A Lack of Antinociceptive or Antiinflammatory Effect of Botulinum Toxin A in an Inflammatory Human Pain Model Anesth. Analg., February 1, 2006; 102(2): 509 - 516. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. D. Iannetti, L. Zambreanu, R. G. Wise, T. J. Buchanan, J. P. Huggins, T. S. Smart, W. Vennart, and I. Tracey From The Cover: Pharmacological modulation of pain-related brain activity during normal and central sensitization states in humans PNAS, December 13, 2005; 102(50): 18195 - 18200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ikeda and K. Murase Glial Nitric Oxide-Mediated Long-Term Presynaptic Facilitation Revealed by Optical Imaging in Rat Spinal Dorsal Horn J. Neurosci., November 3, 2004; 24(44): 9888 - 9896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Serra, M. Campero, H. Bostock, and J. Ochoa Two Types of C Nociceptors in Human Skin and Their Behavior in Areas of Capsaicin-Induced Secondary Hyperalgesia J Neurophysiol, June 1, 2004; 91(6): 2770 - 2781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Wasner, J. Schattschneider, A. Binder, and R. Baron Topical menthol--a human model for cold pain by activation and sensitization of C nociceptors Brain, May 1, 2004; 127(5): 1159 - 1171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Stiasny-Kolster, W. Magerl, W. H. Oertel, J. C. Moller, and R.-D. Treede Static mechanical hyperalgesia without dynamic tactile allodynia in patients with restless legs syndrome Brain, April 1, 2004; 127(4): 773 - 782. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Klein, W. Magerl, H.-C. Hopf, J. Sandkuhler, and R.-D. Treede Perceptual Correlates of Nociceptive Long-Term Potentiation and Long-Term Depression in Humans J. Neurosci., January 28, 2004; 24(4): 964 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ikoma, M. Fartasch, G. Heyer, Y. Miyachi, H. Handwerker, and M. Schmelz Painful stimuli evoke itch in patients with chronic pruritus: Central sensitization for itch Neurology, January 27, 2004; 62(2): 212 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sakai, S. Tomiyasu, H. Yamada, T. Ono, and K. Sumikawa Quantitative and Selective Evaluation of Differential Sensory Nerve Block After Transdermal Lidocaine Anesth. Analg., January 1, 2004; 98(1): 248 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Klede, H. O. Handwerker, and M. Schmelz Central Origin of Secondary Mechanical Hyperalgesia J Neurophysiol, July 1, 2003; 90(1): 353 - 359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ploner, J. Gross, L. Timmermann, and A. Schnitzler Cortical representation of first and second pain sensation in humans PNAS, September 17, 2002; 99(19): 12444 - 12448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Magerl, P. N. Fuchs, R. A. Meyer, and R.-D. Treede Roles of capsaicin-insensitive nociceptors in cutaneous pain and secondary hyperalgesia Brain, September 1, 2001; 124(9): 1754 - 1764. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ringkamp, Y. B. Peng, G. Wu, T. V. Hartke, J. N. Campbell, and R. A. Meyer Capsaicin Responses in Heat-Sensitive and Heat-Insensitive A-Fiber Nociceptors J. Neurosci., June 15, 2001; 21(12): 4460 - 4468. [Abstract] [Full Text] [PDF]
|
|