Actions of cholinergic agonists and antagonists on sensory nerve endings in rat skin, in vitro

1993 ◽  
Vol 70 (1) ◽  
pp. 397-405 ◽  
Author(s):  
K. H. Steen ◽  
P. W. Reeh
Keyword(s):  
Receptive Fields ◽  
Sensory Nerve ◽  
High Threshold ◽  
Rat Skin ◽  
Sensory Afferents ◽  
C Fibers ◽  
High Concentrations ◽  
Cholinergic Agonists And Antagonists ◽  
Cholinergic Effects

1. Cholinergic effects on primary sensory afferents were investigated in a superfused skin-saphenous nerve preparation of the rat that allows the application of chemicals topically to the corium side of identified receptive fields. 2. The acetylcholine analogue carbachol (carbamoylcholine) selectively excited cutaneous C-fibers of nociceptive character; in proportion, almost half of the mechanoheat sensitive ("polymodal," C-MH, n = 27), and a third of the mechanocold sensitive (C-MC, n = 10), and high-threshold mechanosensitive (C-HTM, n = 6) C-fibers were activated. 3. None of slowly and rapidly adapting A beta fibers, low and high threshold mechanoreceptive A delta fibers (n = 19) gave a response to high concentrations (< or = 10(-4) M) of carbachol. 4. The carbachol threshold concentrations of C-nociceptors ranged between 10(-7) and 10(-4) M; 10(-6) M was most frequently encountered. 5. The carbachol-induced discharges showed a dose-response relationship without obvious "ceiling" from 10(-6) to 10(-4) M. Tachyphylaxis was not prominent; the fibers mostly developed ongoing activity after exposure to carbachol. 6. Repeated carbachol treatment of C-MH units left with a marked and sustained desensitization to mechanical (von Frey) stimulation, while the heat responsiveness remained unchanged. 7. In a group of carbachol-sensitive C-nociceptors (n = 4), two units could also be excited with muscarine (10(-6) M), one with nicotine (10(-6) M), and one unit with both substances.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemosensitivity of fine afferents from rat skin in vitro

1990 ◽  
Vol 63 (4) ◽  
pp. 887-901 ◽  
Author(s):  
E. Lang ◽  
A. Novak ◽  
P. W. Reeh ◽  
H. O. Handwerker
Keyword(s):  
Calcium Concentration ◽  
Receptive Fields ◽  
Nerve Fibers ◽  
High Threshold ◽  
Rat Skin ◽  
Test Protocol ◽  
Heat Stimulation ◽  
C Fibers ◽  
Slow Development

1. Properties of sensory receptors with slowly conducting nerve fibers (less than 10 m/s) were studied using a rat skin-saphenous nerve in vitro preparation where receptive fields of identified single units can be isolated and superfused at the corium side with defined chemical solutions. 2. With mechanical search stimuli, 150 slowly adapting units were identified, 88% C-fibers, and the remainder, A delta-fibers. The majority of these units (65%) were categorized as mechano-heat sensitive ("polymodal") with controlled radiant heat stimulation. The remaining units were classified as low- or high-threshold mechanoreceptors according to their von Frey thresholds. 3. Bradykinin (BK), in concentrations of 10(-8) to 10(-4) M, was repeatedly applied for 1 min at 10-min intervals. Fifty-six percent of the polymodal C-fibers responded to BK (up to 10(-5) M), in contrast to 17% of the heat-insensitive units (P less than 0.01). No correlation between BK sensitivity and conduction velocity or von Frey threshold was found. 4. The BK "threshold concentrations" to excite C- and A delta-fibers were about equally distributed over a range from 10(-8) to 10(-5) M. 5. There was a large interindividual variability in pattern and magnitude of the response to BK. Intraindividually, a marked tachyphylaxis upon repeated BK stimulation was observed. 6. In fibers with a slow development of tachyphylaxis, the effects of conditioning application of different chemicals on BK responsiveness were studied. Norepinephrine in 10(-7) M concentration did not produce a significant effect, whereas 10(-5) M and 10(-4) M seemed to increase the BK responses. 7. Prostaglandin E2 (10(-6) M) caused a weak sensitization to BK on average (n.s.), but serotonin (10(-6) M) was clearly effective (P less than 0.05). 8. The strongest sensitization to BK (P = 0.01) resulted from conditioning heat stimulation, which also uncovered a responsiveness in some units initially insensitive to BK. 9. In some experiments the calcium concentration in the superfusate of receptive fields was lowered to 0.3 mM, which induced ongoing activity in C-fibers and markedly increased the BK responses in two polymodal units tested. Increasing the calcium concentration to 3.0 mM reversed these effects. 10. After completing the BK test protocol, polymodal C-fibers were exposed to other chemicals.(ABSTRACT TRUNCATED AT 400 WORDS)

H2O2 sensitivity of afferent splanchnic C fiber units in vitro

1996 ◽  
Vol 76 (1) ◽  
pp. 371-380 ◽  
Author(s):  
D. W. Adelson ◽  
J. Y. Wei ◽  
L. Kruger
Keyword(s):  
Receptive Fields ◽  
Splanchnic Nerve ◽  
Mechanical Stimuli ◽  
H2o2 Treatment ◽  
Response Latencies ◽  
C Fibers ◽  
Afferent Fibers ◽  
Unit Impulse ◽  
Species Production

1. Single-unit impulse activity evoked by transient, focal application of hydrogen peroxide (H2O2) to identified visceral receptive fields has been characterized in an in vitro rat splanchnic nerve-mesentery preparation. In addition to H2O2 responsiveness, units were characterized in terms of sensitivity to mechanical stimuli, warming, and bradykinin. 2. Mesenteric receptive fields of single splanchnic afferent C fibers in vitro were located with the use of warm (approximately 45 degrees C saline) or mechanical search stimuli. After delimitation of the warm-sensitive and/or mechanosensitive receptive field, units were tested for responsiveness to transient, focal application of H2O2. Microliter volumes (usually 1 microliter) of H2O2 (88-880 mM) evoked responses in 25 of 42 (60%) units with identified warm-sensitive and/or mechanosensitive receptive fields, and in an additional 10 units for which H2O2 was the only effective stimulus. 3. Tachyphylaxis to repeated H2O2 stimulation was observed with interstimulus intervals <30 min, but did not indicate irreversible inactivation of the terminal, because 1) during this period warm and mechanical stimuli elicited responses equal to or greater than those before H2O2 treatment, and 2) H2O2 sensitivity was restored after units were allowed to recover. 4. Eight units unresponsive to an initial dose of H2O2 responded vigorously to a repeated application at the same site, suggesting a potentiating effect of prior H2O2 exposure. 5. Sixty-two percent (8 of 13) of H2O2-responsive units, but no (0 of 6) H2O2-unresponsive units responded to transient, focal bradykinin (9-90 nM) application. 6. An indirect mode of H2O2-evoked afferent excitation in some units was suggested by several observations, including the prolonged (up to 8 min) duration of the response of some units to transient H2O2 application, and the occasionally long (>2 min) response latencies to focal application of H2O2 to defined receptive fields. 7. Excitation of splanchnic neurons by H2O2 may be relevant to the modulation of reactive oxygen species production by immunocompetent cells, because sensory neuropeptides contained in these afferent fibers are known to influence the respiratory burst of macrophages and neutrophils.

Excitation of cutaneous sensory nerve endings in the rat by 4-aminopyridine and tetraethylammonium

1992 ◽  
Vol 67 (1) ◽  
pp. 125-131 ◽  
Author(s):  
C. Kirchhoff ◽  
J. D. Leah ◽  
S. Jung ◽  
P. W. Reeh
Keyword(s):  
Potassium Channel ◽  
Sensory Nerve ◽  
Low Frequency ◽  
Threshold Concentration ◽  
Nerve Endings ◽  
Channel Blockers ◽  
C Fibers ◽  
Sensory Nerve Endings ◽  
Potassium Channel Blockers

1. The effects of the potassium channel blockers 4-aminopyridine (4-AP) and tetraethylammonium (TEA) on cutaneous sensory nerve endings have been investigated with the use of an in vitro skin-nerve preparation from the rat. 2. Direct application of these compounds to the nerve endings, but not to the axons, induced continuous discharges in most A beta, A delta, and C fibers. There was no relationship between the fibers' responsiveness or the threshold concentration required to induce discharges and either the conduction velocity or sensory properties of the fibers. 3. The rate of induced discharges increased linearly with increasing concentrations of 4-AP. At threshold concentrations of 10(-6)-10(-5) M, low-frequency, irregular discharges developed; but at the highest concentration of 10(-3) M, a characteristic doublet or bursting discharges usually emerged. 4. During and after the induced discharges there did not appear to be an alteration in the sensitivity of the sensory nerve endings to mechanical or thermal stimuli. 5. It is concluded that the induced activity arises from an action of these potassium channel blockers at or near the action potential generator region at the nerve endings.

Electrophysiological characteristics of primate spinothalamic neurons with renal and somatic inputs

1989 ◽  
Vol 61 (6) ◽  
pp. 1121-1130 ◽  
Author(s):  
W. S. Ammons
Keyword(s):  
Nerve Stimulation ◽  
Receptive Fields ◽  
High Threshold ◽  
Spinothalamic Tract ◽  
Renal Nerve ◽  
C Fibers ◽  
Afferent Fibers ◽  
Renal Nerve Stimulation ◽  
Somatic Receptive Fields ◽  
Stimulation Of

1. Spinothalamic tract (STT) neurons in the T10-L3 segments were studied for responses to renal and somatic stimuli. A total of 90 neurons was studied in 25 alpha-chloralose anesthetized monkeys (Macaca fascicularis). All neurons were antidromically activated from the ventral posterior lateral nucleus of the thalamus. 2. Sixty-two cells were excited by renal nerve stimulation and six inhibited. Probability of locating cells with renal input was greatest in T11-L1. Cells were located in laminae I and IV-VII; however, most were located in laminae V-VII. Antidromic latencies averaged 4.61 +/- 0.32 (SE) ms, whereas antidromic conduction velocities averaged 43.23 +/- 9.03 m/s. 3. Cells with excitatory renal input received A delta input only (36 cells) or A delta- and C-fiber inputs (26 cells). Stimulation of A delta renal afferent fibers evoked bursts of 1-10 spikes/stimulus [mean 3.6 +/- 0.9 spikes/stimulus] with onset latencies of 10.7 +/- 0.5 ms. Stimulation of C-fibers evoked 1.3 +/- 0.5 spikes/stimulus with onset latencies of 61.7 +/- 11.1 ms. Magnitude of responses to A delta-fiber stimulation was greatest in T12 and decreased both rostrally and caudally. Inhibitory responses to renal nerve stimulation required activation of renal C-fibers. 4. All cells that responded to stimulation of renal afferent fibers received convergent inputs from somatic structures. Forty-four cells were classified as wide dynamic range, 10 were high threshold, 12 were high-threshold cells with inhibitory input from hair, 2 were deep, and 2 were low threshold. Somatic receptive fields were large and located on the flank and abdomen and/or the upper hindlimb. Fourteen cells had inhibitory receptive fields located on the contralateral hindlimb or one of the forearms. 5. It is concluded that T11-L1 STT cells in the monkey respond reliably to renal nerve stimulation. Thoracolumbar STT cells may thus play a role in pain that results from renal disease. The locations of the somatic receptive fields of the cells suggest that they are responsible for the referral of renal pain to the flank and abdomen.

Distinct neuron phenotypes may serve object feature sensing in the electrosensory lobe of Gymnotus omarorum

2021 ◽  
Author(s):  
Javier Nogueira ◽  
María E. Castelló ◽  
Carolina Lescano ◽  
Ángel A. Caputi
Keyword(s):  
Stimulus Intensity ◽  
Pyramidal Neurons ◽  
Receptive Fields ◽  
Weakly Electric Fish ◽  
High Threshold ◽  
Electrophysiological Properties ◽  
Clear Cut ◽  
Low Pass ◽  
Object Feature

Early sensory relays circuits in the vertebrate medulla often adopt a cerebellum-like organization specialized for comparing primary afferent inputs with central expectations. These circuits usually have a dual output, carried by center ON and center OFF neurons responding in opposite ways to the same stimulus at the center of their receptive fields. Here we show in the electrosensory lateral line lobe of Gymnotiform weakly electric fish that basilar pyramidal neurons, representing ‘ON’ cells, and non-basilar pyramidal neurons, representing ‘OFF’ cells, have different intrinsic electrophysiological properties. We used classical anatomical techniques and electrophysiological in vitro recordings to compare these neurons. Basilar neurons are silent at rest, have a high threshold to intracellular stimulation, delayed responses to steady state depolarization and low pass responsiveness to membrane voltage variations. They respond to low intensity depolarizing stimuli with large, isolated spikes. As stimulus intensity increases the spikes are followed by a depolarizing after-potential from which phase-locked spikes often arise. Non-basilar neurons show a pacemaker-like spiking activity, smoothly modulated in frequency by slow variations of stimulus intensity. Spike frequency adaptation provides a memory of their recent firing, facilitating non-basilar response to stimulus transients. Considering anatomical and functional dimensions we conclude that basilar and non-basilar pyramidal neurons are clear-cut, different anatomo-functional phenotypes. We propose that, in addition to their role in contrast processing, basilar pyramidal neurons encode sustained global stimuli as those elicited by large or distant objects while non-basilar pyramidal neurons respond to transient stimuli due to movement textured nearby objects.

Segmental and descending influences on intraspinal thresholds of single C-fibers

1979 ◽  
Vol 42 (6) ◽  
pp. 1527-1537 ◽  
Author(s):  
I. D. Hentall ◽  
H. L. Fields
Keyword(s):  
Dorsal Horn ◽  
Receptive Fields ◽  
High Threshold ◽  
Neuronal Responses ◽  
Nucleus Raphe Magnus ◽  
C Fibers ◽  
Raphe Magnus ◽  
Rate Of Decay ◽  
Descending Influences ◽  
Conditioning Stimuli

1. The effect was studied of various conditioning stimuli on the threshold of single C-fibers near their spinal terminals. Spikes were recorded in L6 and L7 dorsal root ganglia of cats. A stimulating electrode in the superficial dorsal horn delivered periodic pulses whose widths were adjusted automatically to near threshold for antidromic spike production. Most units were classified according to their adequate cutaneous stimuli, as C-mechanoreceptors, high-threshold mechanoreceptors, or polymodal nociceptors. 2. Orthodromic activity in all units increased their threshold for up to several minutes; the maximum and rate of decay depended on the amount of activity. This phenomenon parallels the hyperpolarizing afterpotential of C-fibers in peripheral nerve and, we suggest, is probably due to the aftereffect of impulses. 3. Cutaneous conditioning stimuli were applied for 10-20 s near the receptive fields of tested units, but without activating them. During the brushing of skin hair, all threshold changes were decreases; during pinching most changes were increases; during noxious heating the numbers of increases and decreases were similar. It will be necessary to analyze the responses of postsynaptic cells in order to know the physiological significance of these threshold changes. 4. Stimulation in the nucleus raphe magnus caused in half the units higher intraspinal thresholds. If this result is causally related to the previously reported inhibition of neuronal responses in the dorsal horn by the nucleus raphe magnus (NRM), then increased thresholds could reflect either direct presynaptic inhibition or facilitation of inhibitory connections. 5. No correlation between receptive-field classification and the response of terminals to natural cutaneous stimulation or stimulation of the NRM could be discovered. However, the terminals of all kinds of C-fibers differ from A-fibers in their reaction to noxious cutaneous and NRM stimulation, suggesting they are subject to a different system of control.

scholarly journals Cross-effect of TRPV1 and EP3 receptor on coughs and bronchopulmonary C-neural activities

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246375
Author(s):  
Xiuping Gao ◽  
Jianguo Zhuang ◽  
Lei Zhao ◽  
Wan Wei ◽  
Fadi Xu
Keyword(s):  
Sensory Nerve ◽  
Cell Voltage ◽  
Prostaglandin E ◽  
Cross Effect ◽  
C Fibers ◽  
Induced Currents ◽  
The Individual ◽  
Ep3 Receptor

Prostaglandin E2 (PGE2)-induced coughs in vivo and vagal nerve depolarization in vitro are inhibited by systemic and local administration of prostaglandin EP3 receptor (L-798106) and TRPV1 antagonists (JNJ 17203212). These results indicate a modulating effect of TRPV1 on the EP3 receptor-mediated cough responses to PGE2 likely through the vagal sensory nerve. This study aimed to determine whether 1) inhalation of aerosolized JNJ 17203212 and L-798106 affected cough responses to citric acid (CA, mainly stimulating TRPV1) and PGE2; 2) TRPV1 and EP3 receptor morphologically are co-expressed and electrophysiologically functioned in the individual of vagal pulmonary C-neurons (cell bodies of bronchopulmonary C-fibers in the nodose/jugular ganglia); and 3) there was a cross-effect of TRPV1 and EP3 receptor on these neural excitations. To this end, aerosolized CA or PGE2 was inhaled by unanesthetized guinea pigs pretreated without or with each antagonist given in aerosol form. Immunofluorescence was applied to identify the co-expression of TRPV1 and EP3 receptor in vagal pulmonary C-neurons (retrogradely traced by DiI). Whole-cell voltage patch clamp approach was used to detect capsaicin (CAP)- and PGE2-induced currents in individual vagal pulmonary C-neurons and determine the effects of the TRPV1 and EP3 receptor antagonists on the evoked currents. We found that PGE2-induced cough was attenuated by JNJ 17203212 or L-798106 and CA-evoked cough greatly suppressed only by JNJ 17203212. Approximately 1/4 of vagal pulmonary C-neurons co-expressed EP3 with a cell size < 20 μm. Both CAP- and PGE2-induced currents could be recorded in the individuals of some vagal pulmonary C-neurons. The former was largely inhibited only by JNJ 17203212, while the latter was suppressed by JNJ 17203212 or L-798106. The similarity of the cross-effect of both antagonists on cough and vagal pulmonary C-neural activity suggests that a subgroup of vagal pulmonary C-neurons co-expressing TRPV1 and EP3 receptor is, at least in part, responsible for the cough response to PGE2.

Diltiazem blocks the PH-induced excitation of rat nociceptors together with their mechanical and electrical excitability in vitro

1996 ◽  
Vol 75 (1) ◽  
pp. 1-10 ◽  
Author(s):  
H. Wegner ◽  
P. W. Reeh ◽  
S. Brehm ◽  
H. W. Kreysel ◽  
K. H. Steen
Keyword(s):  
Calcium Channel ◽  
Receptive Fields ◽  
Relative Number ◽  
Significant Degree ◽  
Suppressive Effect ◽  
Partial Recovery ◽  
Ph Response ◽  
Sensory Responsiveness ◽  
C Fibers

1. The effect of the calcium channel antagonist diltiazem on pH-induced sustained nociceptor excitation was investigated in a rat skin-saphenous nerve preparation, in vitro, where receptive fields of identified and isolated single fibers were superfused at the corium side with controlled solutions to assess their chemosensitivity. 2. Unmyelinated mechano-heat sensitive ("polymodal") C fiber terminals (n = 78) were superfused with a CO2-saturated synthetic interstitial fluid (CO2-SIF, pH 6.1). Fibers responding to this acid pH condition (n = 60; 77%) were further stimulated for > or = 30 min and additionally treated with diltiazem in various concentrations (10(-6)-10(-3) M) during the middle 10-min period. Usually only one concentration of diltiazem was applied per fiber, although in some cases diltiazem was applied repeatedly and in increasing concentrations. 3. Diltiazem dose-dependently and reversibly reduced the pH-induced sustained nociceptor discharge to a significant degree or completely abolished it. With higher concentrations, both the relative number of units affected and the average amount of suppression were enhanced. The half-maximal blocking concentration (IC50) was estimated to 1.1.10(-4) M diltiazem, the half-maximal concentration for gradual suppression of the pH response was 2.10(-5) M diltiazem. 4. Also, the delay of onset of the suppressive effect decreased with higher diltiazem concentrations. After diltiazem, a partial recovery of the pH-induced discharge was achieved within 10 min depending on the degree of suppression. 5. Before, after, and sometimes during the superfusion, the mechanical (von Frey) thresholds were determined and found to be significantly increased after partial wash out of diltiazem (10(-4) and 10(-3) M; P < 0.006 and P < 0.008, respectively). After 10(-3) M diltiazem superfusion (and 10 min of wash-out), the responsiveness to mechanical stimulation of the majority of the fibers was still totally lost. 6. Heat thresholds were still found to be significantly increased after treatment with diltiazem at 10(-3) and 10(-4) M concentrations (and 10 min of wash out), but appeared unchanged after wash out of lower concentrations. 7. In five mechano-heat-sensitive C fibers, electrical stimulation via a microelectrode placed in the receptive field was used to demonstrate a diltiazem-dose-dependent (10(-5), 10(-4), 10(-3) M) progressive retardation of the nerve conduction velocity and an increase of the electrical threshold. Superfusion for 6 min of diltiazem 10(-5) M was sufficient to block axonal conduction as well as mechanosensitivity, which both recovered synchronously during wash out. 8. It can be concluded from the results that the suppressive effect of diltiazem on pH-induced nociceptor excitation can be explained by a use-dependent axonal block, comparable with the action of local anesthetics and affecting all modalities of sensory responsiveness. 9. The findings provide no indication that a transformed calcium channel specifically sensitive to diltiazem is involved in pH-induced sustained nociceptor excitation.

Sensory receptors with unmyelinated (C) fibers innervating the skin of the rabbit's ear

1985 ◽  
Vol 54 (3) ◽  
pp. 491-501 ◽  
Author(s):  
V. K. Shea ◽  
E. R. Perl
Keyword(s):  
Mechanical Stimulation ◽  
Receptive Fields ◽  
High Threshold ◽  
Cutaneous Stimulation ◽  
Great Auricular Nerve ◽  
C Fibers ◽  
C Fiber ◽  
Back Ground ◽  
Low Threshold ◽  
Stimulation Of

The cutaneous receptive properties of unmyelinated (C) fibers of the rabbit's great auricular nerve were determined by single-unit recordings. The majority of C-fiber units could be excited by cutaneous stimulation, and such sensory units fell into three major categories on the basis of responses to mechanical and thermal stimulation of their cutaneous receptive fields: low-threshold mechanoreceptors, nociceptors, or specific thermoreceptors. The majority of afferent elements were nociceptive, and all nociceptors responded to strong mechanical stimulation. Three types of nociceptors could be distinguished by their responses to thermal stimuli. Polymodal nociceptors responded to heat with thresholds of 40-55 degrees C and typically displayed enhanced responses or sensitization after noxious heating of their receptive fields. High-threshold mechanoreceptors failed to respond promptly to heat before noxious cutaneous stimulation which, however, elicited subsequent back-ground activity or sensitivity to heat. A third type of nociceptor responded to cold but not to heat. Low-threshold mechanoreceptors were identified by their brisk responses to very gentle, slowly moving mechanical stimulation of their receptive fields, and were readily distinguished from any element classified as nociceptive by their lower mechanical thresholds. Rapid innocuous warming or cooling excited some of the low-threshold mechanoreceptors. Specific thermoreceptors, both warming and cooling types, were rare, insensitive to mechanical stimulation, and responded to very slight changes in temperature. In contrast to the sensitization to heat, which was characteristic of most nociceptors, specific warming receptors displayed depressed thermal responses after noxious heating of their receptive fields. These results provide further evidence of the similarity of C-fiber receptors innervating hairy skin of different species. Some differences from past reports and additional features are described.

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