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  • Title: Mechano-sensitive nociceptors are required to detect heat pain thresholds and cowhage itch in human skin.
    Author: Weinkauf B, Dusch M, van der Ham J, Benrath J, Ringkamp M, Schmelz M, Rukwied R.
    Journal: Eur J Pain; 2016 Feb; 20(2):215-22. PubMed ID: 25845368.
    Abstract:
    BACKGROUND: Mechano-sensitive and mechano-insensitive C-nociceptors in human skin differ in receptive field sizes and electrical excitation thresholds, but their distinct functional roles are yet unclear. METHODS: After blocking the lateral femoral cutaneous nerve (NCFL) in eight healthy male subjects (3-mL Naropin(®) 1%), we mapped the skin innervation territory being anaesthetic to mechanical pin prick but sensitive to painful transcutaneous electrical stimuli. Such 'differentially anaesthetic zones' indicated that the functional innervation with mechano-sensitive nociceptors was absent but the innervation with mechano-insensitive nociceptors remained intact. In these areas, we explored heat pain thresholds, low pH-induced pain, cowhage- and histamine-induced itch, and axon reflex flare. RESULTS: In differentially anaesthetic skin, heat pain thresholds were above the cut-off of 50°C (non-anaesthetized skin 47 ± 0.4°C). Pain ratings to 30 μL pH 4 injections were reduced compared to non-anaesthetized skin (48 ± 9 vs. 79 ± 6 VAS; p < 0.01). The axon reflex flare area did not differ between these zones (7.8 ± 1.4 cm(2) vs. 8.3 ± 0.5 cm(2) ). Histamine iontophoresis still caused pruritus in differentially anaesthetized skin in five of eight subjects (VAS 26 ± 14), whereas itch upon cowhage spicules was absent (VAS 0 vs. 29 ± 11 in non-anaesthetized skin). CONCLUSIONS: We conclude that activation of mechano-insensitive nociceptors is sufficient to provoke itch by histamine- and acid-induced pain. The mechano-sensitive nociceptors are crucial for cowhage-induced itch and for the assessment of heat pain thresholds.
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