Sanshool on The Fingertip Interferes with Vibration Detection in a Rapidly-Adapting (RA) Tactile Channel.

An Asian spice, Szechuan pepper (sanshool), is well known for the tingling sensation it induces on the mouth and on the lips. Electrophysiological studies have revealed that its active ingredient can induce firing of mechanoreceptor fibres that typically respond to mechanical vibration. Moreover, a human behavioral study has reported that the perceived frequency of sanshool-induced tingling matches with the preferred frequency range of the tactile rapidly adapting (RA) channel, suggesting the contribution of sanshool-induced RA channel firing to its unique perceptual experience. However, since the RA channel may not be the only channel activated by sanshool, there could be a possibility that the sanshool tingling percept may be caused in whole or in part by other sensory channels. Here, by using a perceptual interference paradigm, we show that the sanshool-induced RA input indeed contributes to the human tactile processing. The absolute detection thresholds for vibrotactile input were measured with and without sanshool application on the fingertip. Sanshool significantly impaired detection of vibrations at 30 Hz (RA channel dominant frequency), but did not impair detection of higher frequency vibrations at 240 Hz (Pacinian-corpuscle (PC) channel dominant frequency) or lower frequency vibrations at 1 Hz (slowly adapting 1 (SA1) channel dominant frequency). These results show that the sanshool induces a peripheral RA channel activation that is relevant for tactile perception. This anomalous activation of RA channels may contribute to the unique tingling experience of sanshool.

Neural system antigens are recognized by autoantibodies from patients affected by a new variant of endemic pemphigus foliaceus in Colombia.

BACKGROUND: Endemic pemphigus foliaceus (EPF), is also known as "fogo selvagem" or "wild fire," reflecting the intense burning sensation of the skin reported by patients with this disease. Based on this finding, we tested for neural autoreactivity in patients affected by a new variant of EPF (El Bagre-EPF). METHODS: We tested 20 El Bagre-EPF patients, 20 normal controls from the endemic area, and 20 age- and sex-matched normal controls from outside the endemic area. We tested for autoreactivity to several immunoglobulins and complement. Both human skin and bovine tail were used as antigens. RESULTS: We detected autoreactivity to neural structures, mechanoreceptors, nerves, perineural cell layers of the arachnoid envelope around the optic nerve, brain structures, and to neuromuscular spindles; these structures colocalized with several neural markers. The patient antibodies also colocalized with desmoplakins 1 and 2, with the armadillo repeat protein deleted in velo-cardio-facial syndrome and with p0071 antibodies. Autoreactivity was also found associated with neurovascular bundles innervating the skin, and immunoelectron microscopy using protein A gold against patient antibodies was positive against the nerve axons. Paucicellularity of the intraepidermal nerve endings and defragmentation of the neural plexus were seen in 70% of the cases and not in the controls from the endemic area (p<0.005). Neuropsychological and/or behavioral symptoms were detected in individuals from the endemic area, including sensorimotor axonal neuropathy. CONCLUSIONS: Our findings may explain for the first time the "pose of pemphigus," representing a dorsiflexural posture seen in EPF patients vis-a-vis the weakness of the extensor nerves, and furthermore, the autoreactivity to nerves in EPF could explain the "burning sensation" encountered in EPF disease.

Vasodilatation in human skin induced by low-amplitude high-frequency vibration.

Vasomotor effects in human skin induced by vibration of low amplitude (10-25 microns) and high frequency (150-250 Hz) have been studied by using skin temperature changes as an approximative measure of variations in skin blood flow. In all tested areas of the body surface, including the face, low-amplitude high-frequency vibration regularly induces vasodilatation. The spatial distribution of the temperature changes induced from different sites of stimulation was studied by infrared thermography. The latencies of the temperature changes, determined by thermistor recordings, were found to vary with site of stimulation and stimulus parameters. The increase in temperature to a given stimulus is greater the lower the prevalent skin temperature, i.e. the increase in blood flow is larger the greater the initial vasomotor tone. The results are in accordance with the view that the vasodilatation is due to a reflex inhibition of pre-existent vasomotor tone in the skin by the afferent inflow from vibration-sensitive mechanoreceptors. High-amplitude vibration (100-200 microns), performed in a few comparative experiments, caused vasoconstriction.

Intensity and frequency characteristics of pacinian corpuscles. III. Effects of tetrodotoxin on transduction process.

This is the third in a series of three papers dealing with intensity and frequency characteristics obtained on pacinian corpuscles isolated from the cat mesentery (8, 9). The experimental results show that tetrodotoxin (TTX) affects not only regenerative action potentials but also the measured receptor (generator) potentials. Extracellularly recorded receptor and action potentials were simultaneously recorded in response to sinusoidal displacement stimuli. Receptor potentials measured in this manner responded with a time course similar to the driving frequency. Since the duration of the action potentials is long relative to the cycle period at high stimulus frequencies, the underlying receptor potentials can become obscured. To prevent this, TTX was applied through superfusion at a concentration of 6.0 microM. After about 30 min, the neural spikes were fully eliminated but the receptor potentials were also decreased in amplitude. Intensity characteristics relating receptor-potential amplitudes to probe displacement amplitudes showed that the percentage decrease in amplitude due to the application of TTX was constant regardless of stimulus intensity. Frequency characteristics relating probe displacement amplitudes to vibration frequency for a constant-response criterion showed an increase in the displacement amplitude required for the criterion response, across frequency, when TTX was applied. On average, the increase was a power function of vibration frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of morphine and leucine-enkephalin on the electrophysiological responses of Pacinian corpuscles of the cat.

The effects of morphine and Leu-enkephalin on the electrical activity of Pacinian corpuscles isolated from cat mesentery were studied. These drugs caused a short-term increase and subsequent decrease of the impulse activity, accompanied by a monotonic growth of the threshold for firing of action potentials and amplitudes of generator and action potentials. Naloxone induced an effect similar to that of morphine. The results obtained indicate that morphine and Leu-enkephalin evoke an increase in membrane potential of a nerve ending. These data may form the basis of the modulating effect of opioid peptides on encapsulated mechanoreceptor activity.

[Cholinesterase activity in the Pacinian corpuscles in denervation and the application of colchicine to the nerve]. / Aktivnost' kholinesteraz tel'tsakh Pachini pri ikh denervatsii i applikatsii kolkhitsina na nerv.

In the Pacinian corpuscles, cholinesterase activity was predominantly revealed along the plasma membrane and in the cytoplasm of the inner core cells. A faint quantity of histochemical end product was detected in the axis cylinder. An increased cholinesterase activity was found after the nerve transection. This change coincides in time with phagocytosis of degenerated axis cylinder by the inner core cells. A decrease in cholinesterase activity was observed in the Pacinian corpuscles after colchicine application to the nerve. This effect may be due to either the blockade of axoplasmic transport of cholinesterase in afferent nerve or/and to the elimination of the trophic influence exerted by the nerve on the cholinesterase activity in the inner care cells.

The effect of Mg2+ and Ca2+ on the excitability of Pacinian corpuscles.

The effect of altering extracellular Ca2+ and Mg2+ levels on electrical properties of Pacinian corpuscles of adult cat has been examined. High Mg2+ solution (5--15 mM) increased the excitability of the receptors and the amplitude of the receptor potential. Ca2+-free EDTA solution caused an increase in the amplitude of the receptor potential in the first 60 min and then its decrease. Mg2+ ions slow down or prevent the depressant effect of the Ca2+ lack on the receptor potential. The phase of the receptor potential amplitude increase in Ca2+-free media was reversibly blocked by tetraethylammonium ions. Treatment with 2,4-dinitrophenol produced a transient increase in the receptor potential amplitude. The threshold of the mechanosensitive receptor membrane was unaffected in Ca2+-free or Mg2+-rich solution. The results suggest that divalent cations are not directly involved in the process of mechanoelectric transformation in Pacinian corpuscles.

Effects of anaesthetics on reflexes elicited in the sudomotor system by stimulation of Pacinian corpuscles and of cutaneous nociceptors.

Sudomotor neurones supplying sweat glands in the hairless skin of the cat's paws can be activated by the cutaneous afferent inputs deriving from vibrational receptors (Pacinian corpuscles) in the paws and from cutaneous nociceptors. Both reflexes probably have separate spinal pathways. In the present investigation the effects of the anaesthetics ketamine, methohexital, chloralose, halothane and Althesin on both types of sudomotor reflexes were examined. For this purpose the skin potentials were recorded from the hairless skin of the paws with Ag--AgCl-electrodes. Before application of any anaesthetic the cats were in a state of light ketamine anaesthesia. The following results were obtained: (1) the resting activity in the sudomotor system and the synchronization of the activity between both hindpaws and between hind- and forepaws were depressed by all anaesthetics to a variable degree. After chloralose application large synchronous potentials of low frequency appeared; (2) ketamine (18--25 mg/kg injected intramuscularly) enhanced the reflexes on vibrational stimulation and depressed the reflexes on noxious stimulation of skin; (3) methohexital (3--10 mg/kg injected intramuscularly) mostly depressed the reflexes on vibrational stimulation and enhanced the reflexes on noxious cutaneous stimuli; (4) chloralose (4.5--20 mg/kg injected intraperitoneally) enhanced both types of reflexes; (5) halothane (1--1.5 vol. %) and Althesin (2.5--5 mg/kg injected intramuscularly) depressed both types of reflexes; (6) in chronic spinal cats ketamine, methohexital and chloralose had a slightly depressive effect on the resting activity of the sudomotor system, but practically no influence on the reflexes induced by cutaneous stimuli; and (7) these results argue that the effects of anaesthetics on the sudomotor system depend on the type of reflex tested and the type of anaesthetic used. They indicate furthermore that the anaesthetics affect largely supraspinal structures and influence the spinal reflex pathways via descending spinal pathways.

[Analysis of the mechanism of amplitude change in Pacinian corpuscle receptor potential in a solution with a decreased calcium ion concentration]. / Analiz mekhanizma izmeneniia amplitudy retseptornogo potentsiala telets Pachini v rastvore s ponizhennoi kontsentratsiei ionov kal'tsiia.

The effect of Ca2+-free solution on the amplitude increase in the receptor potential (RP) of Pacinian corpuscles was studied using external perfusion technique. The RP amplitude increased in Ca2+-free solution. It was blocked after addition of 10-20 mM of tetraethylamonium. A temporary increase in the RP amplitude is seen in the solution with 0.2 mM of 2.4-dinitrophenol. Sensitivity of the receptor membrane to mechanical stimuli does not change in Ca2+-free solution. It is suggested that near the mechanosensitive ionic canal of Pacinian corpuscle receptor membrane the fixed negative charges which could influence the "gate" system state of the mechanosensitive canal are absent.

[Nature of the hyperpotassic composition of the medium surrounding individual tissue mechanoreceptors]. / O prirode giperkalievogo sostava sredy, okruzhaiushchei odinochnye tkanevye mekhanoretseptory.

The ouabain effect on potassium concentration in the Pacini corpuscle fluid was studied using continuous perfusion of cat's mesenteric receptors with ouabain in Ringer's bicarbonate solution. To check the solution penetration into the corpuscles, Na36Cl and (G-3H)-ouabain were used. 2 . 10(-2) mM ouabain reduced (K+) in corpuscle fluid. The high potassium concentration in Pacini corpuscle fluid seems to be due to Na+--K+-ATPase system.

[Effect of magnesium and calcium ions on the electrical activity of Pacinian corpuscles]. / Vliianie ionov magniia i kal'tsiia na élektricheskuiu aktivnost' telets Pachini.

The effect of magnesium and calcium ions of the electrical activity of Pacinian corpuscles was studied in isolated decapsulated preparations. The sensitivity of the corpuscles and the amplitude of receptor potential increased in magnesium-rich solution (5-15 mM). The amplitude of receptor potential increased over the first 60 min and then decreased in calcium-free EDTA solution. Magnesium ions slow down or prevent the depressant effects of the lack of calcium on the receptor potential. Divalent cations are supposed to take no part in mechano-electrical transduction conduction in Pacinian corpuscles.

[Effect of acetylcholine and cholinolytics on the activity of Pacinian corpuscles]. / Vliianie atsetilkholina i kholinolitikov na aktivnost' telets Pachini

The effect of acetylcholine and cholinergic antagonists (atropine, d-tubocurarine, hexamethonium) was studied as applied to isolated decapsulated preparations. Acetylcholine (10(-5)-10(-4) g/ml) enhanced the sensitivity of the receptors to mechanical stimuli due to increased excitability of the Ranvier node. The amplitude of the receptor potential decreased. Cholinergic drugs did not block the responses of receptors to mechanical stimuli. The results provide evidence against the role of acetylcholine as a transmitter in the Pacinian corpuscles.

[The effect of cholinergic substances on individual mechanoreceptors--Pacinian corpuscles]. / Vliianie kholinergicheskikh veshchestv na odinochnye mekhanoretseptory--tel'tsa Pachini

Acetylcholine and nicotine application to the intact pacinian corpuscle failed to stimulate the spike activity, but changed the sensitivity to the mechanical stimulation: low concentration (1.10(-6) g/ml) increased the sensitivity and high concentration (1.10(-4) g/ml) decreased it. This influence can be attributed to the action of these substances on the structures which generate the action potentials. Acetylcholine application to decapsulated pacinian corpuscles stimulated the appearance of the spike activity. This reaction was possibly connected with the acetylcholine influence on the mechanoreceptive zones proper. Tubocurarine or hexonium application of decapsulated pacinian corpuscles led to depression of the sensitivity of the receptor to the mechanical stimulation that can also be explained by the participation of acetylcholine in the process of adequate receptor stimulation.