title: Secondary hyperalgesia to punctate mechanical stimuli. Central sensitization to A-fibre nociceptor input.
abstract: 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 microg capsaicin, and pain sensitivity in adjacent skin was tested with 200 micron 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.
authors.affiliation: Institute of Physiology and Pathophysiology,Johannes Gutenberg University, Mainz, Germany.
authors.forename: E A
authors.initials: EA
authors.lastname: Ziegler
authors.forename: W
authors.initials: W
authors.lastname: Magerl
authors.forename: R A
authors.initials: RA
authors.lastname: Meyer
authors.forename: R D
authors.initials: RD
authors.lastname: Treede
mesh_terms: D000328:Adult; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000503:physiopathology* / Q000523:psychology; D008297:Male; D008875:Middle Aged; D009407:Nerve Block / Q000379:methods; D009431:Neural Conduction / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010147:Pain Measurement / Q000379:methods; D011826:Radial Nerve / Q000187:drug effects / Q000293:injuries / Q000502:physiology; D014110:Touch / Q000187:drug effects / Q000502:physiology*
chemical_list: D002211:Capsaicin