Axon reflex vasodilatation due to transcutaneous electrical stimulation in human skin was measured by laser Doppler imaging. Constant current pulses of 10 mA, 0.2 ms, delivered at 1 or 10 Hz for 2 min through a probe of 30 mm2 surface area did not induce a significant flare response, though this stimulus previously has been found supra-maximal for cutaneous polymodal (mechano-heat responsive) C-nociceptors in microneurography experiments. Pulses of the same strength from a pointed probe yielding a higher current density induced an extended and persistent flare. This type of stimulus previously has been proven to recruit mechano-insensitive C-units in microneurography experiments, in contrast to stimuli from the 30 mm2 probe. It is concluded that mechano-insensitive C-nociceptors and not polymodal C-units mediate the axon reflex flare in human skin.

No abstract

To investigate the role of trigeminal subnucleus caudalis in neural mechanisms of irritation, we recorded single-unit responses to application of a variety of irritant chemicals to the tongue or ocular mucosa in thiopental-anesthetized rats. Recordings were made from wide dynamic range (WDR) and nociceptive-specific units in superficial layers of the dorsomedial caudalis (0-3 mm caudal to obex) responsive to mechanical stimulation and noxious heating of the ipsilateral tongue ("tongue" units) and from WDR units in ventrolateral caudalis (0-2 caudal to obex) responsive to mechanical and noxious thermal stimulation of cornea-conjunctiva and frequently also surrounding skin ("cornea-conjunctival" units). The following chemicals were delivered topically (0.1 ml) onto the dorsal anterior tongue or instilled into the ipsilateral eye: capsaicin (0.001-1% = 3.3 x 10(-2) to 3.3 x 10(-5) M), ethanol (15-80%), histamine (0.01-10% = 9 x 10(-1) to 9 x 10(-4) M), mustard oil (allyl-isothiocyanate, 4-100% = 4 x 10(-1) to 10 M), NaCl (0.5-5 M), nicotine (0.01-10% = 6 x 10(-1) to 6 x 10(-4) M), acidified phosphate buffer (pH 1-6), piperine (0.01-1% = 3.5 x 10(-2) to 3.5 x 10(-4) M), serotonin (5-HT; 0.3-3% = 1.4 x 10(-1) to 1.4 x 10(-2) M), and carbonated water. The dose-response relationship and possible tachyphylaxis were tested for each chemical. Of 32 tongue units, 31 responded to one or more, and frequently all, chemicals tested. The population responded to 75.3% of the various chemicals tested (

Little is known about the contribution of C-afferent fibres to chronic painful conditions in humans. We sought to investigate the role of C-fibres in the pathophysiology of pain and hyperalgesia in erythromelalgia as a model disease for chronic pain. Erythromelalgia is a condition characterized by painful, red and hot extremities, and patients often report tenderness on walking. We made microneurographic recordings from single C-fibres in cutaneous fascicles of the peroneal nerve in patients suffering from this disease. All patients had had a pain attack recently and psychophysical signs of allodynia and punctate hyperalgesia were found. We obtained recordings from a total of 103 C-fibres and found significantly lower conduction velocities and increased activity-dependent slowing of the conduction velocity of afferent C-fibres in the patients compared with healthy controls. Furthermore, several units with biophysical properties of mechano-insensitive fibres were pathological, being spontaneously active or sensitized to mechanical stimuli. Since these fibres also mediate the axon reflex flare, their hyperexcitability might account not only for ongoing pain and tenderness but also for redness and warming in this pain syndrome. The changes in conductive properties found in the C-fibres of these patients could be the first signs of a small-fibre neuropathy. This is the first systematic study of single C-fibres in patients and it shows an active contribution of mechano-insensitive fibres to chronic pain.

SUMMARY1. The proportion of primary afferent nerve fibres in a skin nerve of the rat that responded or failed to respond to mechanical or thermal stimulation of the skin in the noxious and non-noxious range was analysed.2. Activity of afferent nerve fibres was recorded from the dorsal roots. Units projecting into the sural nerve were selected using supramaximal electrical stimulation of the nerve stem. All other hindleg nerves were cut.3. The receptive fields were searched by carefully examining the hindleg skin with noxious and innocuous mechanical, cooling and warming stimuli. Probing of the intrinsic foot muscles and manipulation of the ankle and toe joints was employed to recruit units projecting to deeper tissues.4. In a first series of twenty-two experiments, eighty-nine rapidly conducting myelinated A,f units, thirty slowly conducting myelinated Ad units and 101 unmyelinated C units were investigated. Most units were identified as belonging to one of the established classes of cutaneous sensory units and this was also ascertained by a collision test. 5. Two Aft, eight Ad and forty-six C fibres did not respond to any one of the stimuli. Electrical thresholds and conduction velocities of the unresponsive C fibres were not significantly different from those of the units responding to natural stimulation of their receptive fields. In the Ad group unresponsive and high threshold mechanoreceptive units were preferentially found among the units with the slowest conduction velocities.6. In a second series of seven experiments, one single nerve filament containing responsive and unresponsive C fibres was tested repetitively at 30 min intervals. Twenty unresponsive units and seven units responding to noxious mechanical and/or heat stimuli were studied. Ten of the twenty initially unresponsive units became activated by mechanical and/or heat stimuli after observation times of 30-150 min.