Chronic Estrogen Sensitizes a Subset of Mechanosensitive Afferents Innervating the Uterine Cervix

2005 ◽  
Vol 93 (4) ◽  
pp. 2167-2173 ◽  
Author(s):  
Baogang Liu ◽  
James C. Eisenach ◽  
Chuanyao Tong
Keyword(s):  
Spontaneous Activity ◽  
Uterine Cervix ◽  
Firing Frequency ◽  
High Threshold ◽  
Group 13 ◽  
Ovx Rats ◽  
Afferent Fibers ◽  
Low Threshold ◽  
Group 5 ◽  
Afferent Response

Estrogen increases reflex nocifensive responses to distension of the uterus and the urinary bladder, but estrogen's effects on afferent response to distension of the uterine cervix, the site of obstetric and some gynecologic pain, has not been studied. Here, single fiber recording of hypogastric nerve responses to uterine cervical distension were obtained from ovariectomized (OVX) rats and OVX rats treated with estrogen (ES). Spontaneous activity was greater in the ES group (13 of 24 units; 54%) than in the OVX group (6 of 27 units; 22%). ES differentially altered the response of low- and high-threshold units to distension. For high-threshold units, firing frequency was increased two- to fourfold with 60–100 gm distension in ES compared with OVX groups ( P < 0.05). In contrast, the response of low-threshold units to distension was not altered by ES. About one-half of units tested in each group responded to a temperature increase from 35 to 49°C. A greater proportion of thermosensitive units were also mechanosensitive in the ES group (7 of 8 afferents, 88%) than in the OVX group (5 of 11 afferents, 45%). Acute application of ES in OVX rats failed to evoke or increase distension-induced responses. These data show the polymodal nature of afferent fibers innervating the uterine cervix. Increased spontaneous activity with ES may play a part in remodeling of the cervical tissue, whereas selective sensitization of high-threshold units by ES might underlie increased pain responses to cervical distension. Failure of acute ES treatment to mimic this suggests a genomic effect.

Mormyromast electroreceptor organs and their afferent fibers in mormyrid fish. III. Physiological differences between two morphological types of fibers

1990 ◽  
Vol 63 (2) ◽  
pp. 319-332 ◽  
Author(s):  
C. C. Bell
Keyword(s):  
Tuning Curve ◽  
Conditioning Stimulus ◽  
Receptor Potential ◽  
Sensory Cells ◽  
High Threshold ◽  
Afferent Fibers ◽  
Mormyrid Fish ◽  
Spike Number ◽  
Low Threshold ◽  
Physiological Differences

1. Mormyromast electroreceptor organs in electric fish of the family Mormyridae have two types of separately innervated sensory cells, the A and B sensory cells of Szabo and Wersall. The first paper in this series showed anatomically that afferent fibers from the two types of sensory cell terminate centrally in separate zones of the electrosensory lateral line lobe (ELL), fibers from A cells terminating in the medial zone and fibers from B cells terminating in the dorsolateral zone. The goal of the present study was to determine the physiological differences between the two morphologically distinct types of mormyromast afferent fibers. 2. The present study has two parts. In the first part, mormyromast fibers were recorded near their central terminals in the two mormyromast zones of ELL. In the second part, mormyromast fibers were recorded from a peripheral electrosensory nerve. In both parts, various electrosensory stimuli were delivered and voltage thresholds were measured at the electroreceptor. 3. In the first part of the study, mormyromast fibers terminating in the two central zones were found to be different in their thresholds and in the maximum number of spikes evoked by a single stimulus. Afferent fibers terminating in the medial zone, which arise from A sensory cells, had higher thresholds and smaller maximum spike numbers than fibers terminating in the dorsolateral zone, which arise from B sensory cells. 4. In the second part of the study, the same two groups of fibers--one group with a high threshold and a small maximum spike number, and a second group with a low threshold and a large maximum spike number--were identified in extracellular recordings from a peripheral electrosensory nerve. The thresholds of the two groups were quite distinct, allowing the fibers to be divided into high- and low-threshold groups, which most likely represent the fibers from the A and B sensory cells, respectively. 5. The high- and low-threshold groups of fibers recorded from peripheral nerve were found to be different in a number of additional properties besides threshold and maximum spike number. Additional differences were found in the following properties: strength-duration curve, correlation with a receptor potential recorded at the electroreceptor, tuning curve, and short latency facilitation by a conditioning stimulus. Thus there appear to be several physiological differences between mormyromast afferent fibers from A and B sensory cells, in addition to the differences in threshold and spike number.(ABSTRACT TRUNCATED AT 400 WORDS)

Interdependency between mechanical parameters and afferent nerve discharge in hypertrophic intestine of rats

2016 ◽  
Vol 310 (6) ◽  
pp. G376-G386 ◽  
Author(s):  
Jian Yang ◽  
Jingbo Zhao ◽  
Pengmin Chen ◽  
Toshiya Nakaguchi ◽  
David Grundy ◽  
...  
Keyword(s):  
Intestinal Obstruction ◽  
Afferent Nerve ◽  
High Threshold ◽  
Creep Tests ◽  
Tissue Properties ◽  
Stimulus Response ◽  
Afferent Fibers ◽  
Afferent Response ◽  
Partial Intestinal Obstruction ◽  
Nerve Discharge

Partial intestinal obstruction causes smooth muscle hypertrophy, enteric neuronal plasticity, motility disorders, and biomechanical remodeling. In this study we characterized the stimulus-response function of afferent fibers innervating the partially obstructed jejunum. A key question is whether changes in afferent firing arise from remodeled mechanical tissue properties or from adaptive afferent processes. Partial obstruction was created by placing a polyethylene ring for 2 wk in jejunum of seven rats. Sham obstruction was made in six rats and seven rats served as normal controls. Firing from mesenteric afferent nerve bundles was recorded during mechanical ramp, relaxation, and creep tests. Stress-strain, spike rate increase ratio (SRIR), and firing rate in single units were assessed for evaluation of interdependency of the mechanical stimulations, histomorphometry data, and afferent nerve discharge. Partial intestinal obstruction resulted in hypertrophy and jejunal stiffening proximal to the obstruction site. Low SRIR at low strains during fast distension and at high stresses during slow distension was found in the obstructed rats. Single unit analysis showed increased proportion of mechanosensitive units but absent high-threshold (HT) units during slow stimulation, decreased number of HT units during fast stimulation, and shift from HT sensitivity towards low threshold sensitivity in the obstructed jejunum. Biomechanical remodeling and altered afferent response to mechanical stimulations were found in the obstructed jejunum. Afferents from obstructed jejunum preserved their function in encoding ongoing mechanical stimulation but showed changes in their responsiveness. The findings support that mechanical factors rather than adaption are important for afferent remodeling.

Characterization of mechanosensitive pelvic nerve afferent fibers innervating the colon of the rat

1994 ◽  
Vol 71 (6) ◽  
pp. 2046-2060 ◽  
Author(s):  
J. N. Sengupta ◽  
G. F. Gebhart
Keyword(s):  
Regression Line ◽  
High Threshold ◽  
Pelvic Nerve ◽  
Stimulus Response ◽  
C Fibers ◽  
Afferent Fibers ◽  
Low Threshold ◽  
Resting Activity ◽  
Stimulation Of

1. Single-unit activity was recorded from S1 sacral dorsal root afferent fibers in the anesthetized rat. A total of 364 afferent fibers were identified by electrical stimulation of the pelvic nerve and subsequently tested for response to colorectal distension (CRD) and urinary bladder distension (UBD). Sixty-seven percent (n = 244) of the fibers were unmyelinated C-fibers and 33% (n = 120) were thinly myelinated A delta-fibers. 2. In three initial experiments, 35 fibers were identified by pelvic nerve stimulation and tested for response only to CRD; none of these fibers responded to CRD. In 20 subsequent experiments, 329 pelvic nerve afferent fibers were tested for response to CRD and UBD. Thirty-four percent (n = 112) of the 329 fibers were unresponsive to noxious CRD (80 mmHg) or to UBD (slow filling < or = 100 mmHg), 44% (n = 146) responded to UBD, 16% (n = 53) responded to CRD, and 6% (n = 18) responded to mechanical stimulation of the anal mucosa. 3. Of the total of 53 pelvic nerve afferent fibers that responded to CRD, 43 (81%) were C-fibers (mean: 1.5 m/s) and 10 (19%) were A delta-fibers (mean: 4.7 m/s). Fifteen of the CRD-sensitive fibers had no resting activity, whereas 38 fibers exhibited some resting activity (mean: 2.6 imp/s). 4. Reproducibility of responses to repeated CRD (80 mmHg, 30s, 10 trials at 4-min intervals) was tested in 17 fibers. In 16, responses to repeated distension were reproducible without evidence of facilitation or inhibition of subsequent responses. One fiber gave greater responses during the 9th and 10th trials. 5. Responses to graded CRD were studied in 44 fibers. All fibers exhibited monotonic, increasing stimulus-response functions < or = 80 mmHg of distension. Thresholds for response of the 44 fibers were determined after extrapolation of the least-squares linear-regression line to the ordinate and varied between 0 and 40 mmHg. Two populations of pelvic nerve afferent fibers in the colon were apparent: low threshold (LT) afferent fibers had a mean threshold of 2.9 mmHg (range: 0-10 mmHg; n = 34) and high threshold (HT) afferent fibers had a mean threshold of 32.6 mmHg (range: 28.0–40.0 mmHg; n = 10). 6. Chemosensitivity to bradykinin (BK) was tested in nine LT fibers. Seven fibers responded to BK (0.1 to 100 micrograms/kg ia) and two fibers did not respond up to 100 micrograms/kg of BK. Responses to BK tested in three fibers were dose dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Electrophysiological and neuroanatomical evidence of sexual dimorphism in aortic baroreceptor and vagal afferents in rat

2008 ◽  
Vol 295 (4) ◽  
pp. R1301-R1310 ◽  
Author(s):  
Bai-Yan Li ◽  
Guo-Fen Qiao ◽  
Bin Feng ◽  
Rui-Bo Zhao ◽  
Yan-Jie Lu ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Neuronal Excitability ◽  
Initial Step ◽  
Nerve Fibers ◽  
Vagal Afferents ◽  
Male Rats ◽  
High Threshold ◽  
Afferent Fibers ◽  
Low Threshold ◽  
Clamp Study

Evidence for sexual dimorphism in autonomic control of cardiovascular function is both compelling and confounding. Across healthy and disease populations sex-associated differences in neurocirculatory hemodynamics are far too complex to be entirely related to sex hormones. As an initial step toward identifying additional physiological mechanisms, we investigated whether there is a sex bias in the relative expression of low-threshold-myelinated and high-threshold-unmyelinated aortic baroreceptor afferents in rats. These two types of afferent fibers have markedly different reflexogenic effects upon heart rate and blood pressure and thus the potential impact upon baroreflex dynamics could be substantial. Our results, using a combination of a patch-clamp study of fluorescently identified aortic baroreceptor neurons (ABN) and morphometric analysis of aortic baroreceptor nerve fibers, demonstrate that females exhibit a greater percentage of myelinated baroreceptor fibers (24.8% vs. 18.7% of total baroreceptor fiber population, P < 0.01) and express a functional subtype of myelinated ABN rarely found in age-matched males (11% vs. 2.3%, n = 107, P < 0.01). Interestingly, this neuronal phenotype is more prevalent in the general population of female vagal afferent neurons (17.7% vs. 3.8%, n = 169, P < 0.01), and ovariectomy does not alter its expression but does lessen neuronal excitability. These data suggest there are fundamental neuroanatomical and electrophysiological differences between aortic baroreceptor afferents of female and male rats. Possible explanations are presented as to how such a greater prevalence of low-threshold myelinated afferents could be a contributing factor to the altered baroreflex sensitivity and vagal tone of females compared with males.

Nociceptors and Chronic Pain

2021 ◽  
Author(s):  
Edgar T. Walters
Keyword(s):  
Chronic Pain ◽  
Spontaneous Activity ◽  
Intracellular Signaling ◽  
Chronic Conditions ◽  
Spontaneous Pain ◽  
Pain Pathways ◽  
Low Threshold ◽  
Highly Correlated ◽  
Hyperalgesic Priming ◽  
Peripheral Activation

Chronic pain lasting months or longer is very common, poorly treated, and sometimes devastating. Nociceptors are sensory neurons that usually are silent unless activated by tissue damage or inflammation. In humans their peripheral activation evokes conscious pain, and their spontaneous activity is highly correlated with spontaneous pain. Persistently hyperactive nociceptors mediate increased responses to normally painful stimuli (hyperalgesia) in chronic conditions and promote the sensitization of central pain pathways that allows low-threshold mechanoreceptors to elicit painful responses to innocuous stimuli (allodynia). Investigations of rodent models of neuropathic pain and hyperalgesic priming have revealed many alterations in nociceptors and associated cells that are implicated in the development and maintenance of chronic pain. These include chronic nociceptor hyperexcitability and spontaneous activity, sprouting, synaptic plasticity, changes in intracellular signaling, and modified responses to opioids, along with alterations in the expression and translation of thousands of genes in nociceptors and closely linked cells.

Electrophysiology of neurosecretory cells from the pituitary intermediate lobe

1988 ◽  
Vol 139 (1) ◽  
pp. 317-328
Author(s):  
R. N. McBurney ◽  
S. J. Kehl
Keyword(s):  
Cell Cultures ◽  
Calcium Ion ◽  
Action Potentials ◽  
Neurosecretory Cells ◽  
Secretory Process ◽  
High Threshold ◽  
Pars Intermedia ◽  
Low Threshold ◽  
Stimulus Secretion Coupling ◽  
Ca2 Channels

One of the goals in studying the electrical properties of neurosecretory cells is to relate their electrical activity to the process of secretion. A central question in these studies concerns the role of transmembrane calcium ion flux in the initiation of the secretory event. With regard to the secretory process in pituitary cells, several research groups have addressed this question in vitro using mixed primary anterior pituitary cell cultures or clonal cell lines derived from pituitary tumours. Other workers, including ourselves, have used homogeneous cell cultures derived from the pituitary intermediate lobes of rats to examine the characteristics of voltage-dependent conductances, the contribution of these conductances to action potentials and their role in stimulus-secretion coupling. Pars intermedia (PI) cells often fire spontaneous action potentials whose frequency can be modified by the injection of sustained currents through the recording electrode. In quiescent cells action potentials can also be evoked by the injection of depolarizing current stimuli. At around 20 degrees C these action potentials have a duration of about 5 ms. Although most of the inward current during action potentials is carried by sodium ions, a calcium ion component can be demonstrated under abnormal conditions. Voltage-clamp experiments have revealed that the membrane of these cells contains high-threshold, L-type, Ca2+ channels and low-threshold Ca2+ channels. Since hormone release from PI cells appears not to be dependent on action potential activity but does depend on external calcium ions, it is not clear what role these Ca2+ channels play in stimulus-secretion coupling in cells of the pituitary pars intermedia. One possibility is that the low-threshold Ca2+ channels are more important to the secretory process than the high-threshold channels.

Metabotropic glutamate receptor-mediated suppression of L-type calcium current in acutely isolated neocortical neurons

1992 ◽  
Vol 68 (3) ◽  
pp. 833-842 ◽  
Author(s):  
R. J. Sayer ◽  
P. C. Schwindt ◽  
W. E. Crill
Keyword(s):  
Glutamate Receptor ◽  
Pyramidal Neurons ◽  
Metabotropic Glutamate Receptor ◽  
High Threshold ◽  
External Application ◽  
Metabotropic Glutamate ◽  
Neocortical Neurons ◽  
Old Rats ◽  
Low Threshold ◽  
Ca2 Channels

1. The effects of metabotropic glutamate receptor (mGluR) stimulation on whole-cell Ca2+ currents were studied in pyramidal neurons isolated from the dorsal frontoparietal neocortex of rat. The selective mGluR agonist cis-(+/-)-1-aminocyclopentane-1,3-dicarboxylic acid [trans-ACPD (100 microM)] suppressed the peak high-threshold Ca2+ current by 21 +/- 1.7% (mean +/- SE) in 40 of 43 cells from 10- to 21-day-old rats. Consistent with previous findings for mGluR, glutamate, quisqualate, and ibotenate [but not alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)] reduced the Ca2+ currents, and the responses were not blocked by the ionotropic glutamate receptor antagonists 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) and DL-2-amino-5-phosphonovaleric acid (APV). EC50S for Ca2+ current suppression were 29 nM for quisqualate, 2.3 microM for glutamate, and 13 microM for trans-ACPD. 2. The low-threshold Ca2+ current was not modulated by trans-ACPD. The component of the high-threshold CA2+ current suppressed by mGluR was determined by pharmacology; the responses were not affected by omega-conotoxin GVIA but were occluded by the dihydropyridine Ca2+ antagonist nifedipine. Ca2+ tail currents prolonged by the dihydropyridine Ca2+ agonist (+)-SDZ 202-79] were suppressed by mGluR stimulation in parallel with the peak current. These findings strongly suggest that L-type Ca2+ channels are modulated by mGluR. 3. In neurons dialyzed with 100 microM guanosine 5'-(gamma-thio)triphosphate (GTP-gamma-S), Ca2+ current suppression was elicited by the first application of trans-ACPD (in 5 of 6 cells), but not by subsequent applications. Responses in neurons dialyzed with 2 mM guanosine 5'-(beta-thio)diphosphate (GDP-beta-S) were significantly smaller than controls. The results are consistent with mGluR acting via linkage to a G protein. 4. The responses to mGluR agonists were smaller when the external Ca2+ was replaced by Ba2+, indicating that some part of the mechanism underlying the current suppression is Ca2+ dependent. Because mGluR stimulates phosphoinositide turnover and release of Ca2+ from intracellular stores in other types of neurons, the possibility of released Ca2+ mediating inactivation of Ca2+ channels was considered. However, the Ca2+ current suppression was not attenuated by strong intracellular Ca2+ buffering [20 mM bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA)], by dialysis with 100 microM inositol-1,4,5-triphosphate (IP3), or by external application of 1 microM thapsigargin. 5. We conclude that in neocortical neurons, one action of mGluR is to suppress the component of high-threshold Ca2+ current conducted by L-type Ca2+ channels.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Long-term regulation of calcium channels in clonal pituitary cells by epidermal growth factor, insulin, and glucocorticoids.

1994 ◽  
Vol 104 (6) ◽  
pp. 1019-1038 ◽  
Author(s):  
U Meza ◽  
G Avila ◽  
R Felix ◽  
J C Gomora ◽  
G Cota
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Current Density ◽  
Threshold Current ◽  
Gh3 Cells ◽  
High Threshold ◽  
Ca Channels ◽  
Regulatory Factors ◽  
Epidermal Growth ◽  
Low Threshold

In rat pituitary GH3 cells, epidermal growth factor (EGF) and insulin stimulate prolactin production, whereas glucocorticoids exert the opposite effect. In the present study, GH3 cells were subjected to whole-cell patch clamp to assess the chronic actions of such regulatory factors on voltage-dependent calcium currents. Before the electrical recording, cells were grown 5-6 d either under standard conditions or in the presence of 5 nM EGF, 100 nM insulin, 1 microM dexamethasone or 5 microM cortisol. EGF induced a twofold selective increase in high-threshold calcium current density. Insulin and glucocorticoids, on the other hand, specifically regulated low-threshold Ca channels. Current density through these channels increased by 70% in insulin-treated cells, and decreased by 50% in cells exposed to dexamethasone or cortisol. Other Ca channel properties investigated (conductance-voltage curves, deactivation rates, time course and voltage dependence of low-threshold current inactivation) were unaffected by the chemical messengers. The alterations in current density persisted for many hours after removing the regulatory factors from the culture medium. In fact, the stimulatory action of EGF on high-threshold current lasted &gt; 3 d. The results suggest that the control of prolactin production by the factors tested involves regulation of the surface density of functional Ca channels in the plasma membrane.

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