Mechanical sensitization, increased axonal excitability, and spontaneous activity in C-nociceptors after ultraviolet B irradiation in pig skin.

Ultraviolet B (UVB) irradiation induces hyperalgesia in human and animal pain models. We investigated mechanical sensitization, increase in axonal excitability, and spontaneous activity in different C-nociceptor classes after UVB in pig skin. We focused on units with receptive fields covering both irradiated and nonirradiated skin allowing intraindividual comparisons.

Maximum axonal following frequency separates classes of cutaneous unmyelinated nociceptors in the pig.

Key Points: C-nociceptors are generally assumed to have a low maximum discharge frequency of 10-30 Hz. However, only mechano-insensitive 'silent' C-nociceptors cannot follow electrical stimulation at 5 Hz (75 pulses) whereas polymodal C-nociceptors in the pig follow stimulation at up to 100 Hz without conduction failure. Sensitization by nerve growth factor increases the maximum following frequency of 'silent' nociceptors in pig skin and might thereby contribute in particular to intense pain sensations in chronic inflammation.

TTX-Resistant Sodium Channels Functionally Separate Silent From Polymodal C-nociceptors.

Pronounced activity-dependent slowing of conduction has been used to characterize mechano-insensitive, "silent" nociceptors and might be due to high expression of Na1.8 and could, therefore, be characterized by their tetrodotoxin-resistance (TTX-r). Nociceptor-class specific differences in action potential characteristics were studied by: (i) calcium imaging in single porcine nerve growth factor (NGF)-responsive neurites; (ii) extracellular recordings in functionally identified porcine silent nociceptors; and (iii) patch-clamp recordings from murine silent nociceptors, genetically defined by nicotinic acetylcholine receptor subunit alpha-3 (CHRNA3) expression.

Nerve growth factor locally sensitizes nociceptors in human skin.

Nerve growth factor (NGF) injected into the human skin causes local hyperalgesia to mechanical and electrical stimuli lasting for weeks. Pig data suggested axonal sensitization of C-nociceptors as a contributing mechanism. Here, we recorded single C-nociceptors in 11 human subjects 3 weeks after intracutaneous injection of 1 μg NGF into the foot dorsum.