Mechanosensitive properties of pelvic nerve afferent fibers innervating the urinary bladder of the rat

1994 ◽  
Vol 72 (5) ◽  
pp. 2420-2430 ◽  
Author(s):  
J. N. Sengupta ◽  
G. F. Gebhart

1. Single-unit activity was recorded from S1 dorsal root afferent fibers in pentobarbital-anesthetized rats. In 25 experiments, 245 afferent fibers were identified by electrical stimulation of the pelvic nerve. Fifty-two percent were C fibers (conduction velocity: 1.70 +/- 0.04 m/s; mean +/- SE) and 48% were A delta-fibers (conduction velocity: 11.07 +/- 0.95 m/s). 2. Of 245 pelvic nerve afferent fibers, 92 (38%) responded to noxious urinary bladder distension (UBD; 80 mmHg); 57 of these fibers were C fibers and 35 were A delta-fibers. Forty-four fibers responded to colorectal distension (CRD; 80 mmHg); 32 were C fibers and 12 were A delta-fibers. A total of 39 fibers were identified in the anal mucosa; 3 were C fibers and 36 were A delta-fibers. Seventy fibers (28%) in these experiments were unresponsive to either UBD or CRD or to probing of the anal mucosa; 32 were unmyelinated C fibers and 38 were A delta-fibers. 3. Reproducibility of responses to repeated UBD (80 mmHg, 20 s; 8 trials at 4-min intervals) was tested in 10 fibers. In nine fibers, responses to repeated distension did not change; one fiber exhibited a progressive decrease in response magnitude after the third trial. 4. Of the 92 afferent fibers that responded to UBD, 45 were further characterized for responses to graded intensities of UBD. Forty fibers had some resting activity (1.7 +/- 0.3 impulses/s) and five fibers exhibited no ongoing activity. The response to UBD adapted slowly during the 20-s period of phasic UBD or during slow isotonic filling of the bladder. 5. The stimulus-response function (SRF) of fibers (n = 45) to graded UBD was monotonic < or = 80 mmHg. Thresholds for responses were determined after extrapolation of the least-squares linear regression line to the ordinate, and varied between 0 and 45 mmHg. The frequency distribution profile of thresholds revealed two populations of pelvic nerve afferent fibers in the urinary bladder: a larger group (n = 36) of low-threshold (LT) fibers (5.7 +/- 1.0 mmHg) and a smaller group (n = 9) of high-threshold (HT) fibers (34 +/- 2.5 mmHg). 6. Responses of four LT fibers to graded UBD were tested before and 30 min after instillation of 0.5 ml of 0.5% acetic acid (pH 3) into the bladder. The mean threshold for response of these fibers before instillation of acetic acid (9.4 +/- 3.1 mmHg) more than doubled (to 22.3 +/- 6.7 mmHg) after instillation of acetic acid.(ABSTRACT TRUNCATED AT 400 WORDS)

1994 ◽  
Vol 71 (6) ◽  
pp. 2046-2060 ◽  
Author(s):  
J. N. Sengupta ◽  
G. F. Gebhart

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)


1997 ◽  
Vol 78 (4) ◽  
pp. 1841-1850 ◽  
Author(s):  
Martin Koltzenburg ◽  
Cheryl L. Stucky ◽  
Gary R. Lewin

Koltzenburg, Martin, Cheryl L. Stucky, and Gary R. Lewin. Receptive properties of mouse sensory neurons innervating hairy skin. J. Neurophysiol. 78: 1841–1850, 1997. Using an in vitro nerve skin preparation and controlled mechanical or thermal stimuli, we analyzed the receptive properties of 277 mechanosensitive single primary afferents with myelinated ( n = 251) or unmyelinated ( n = 26) axons innervating the hairy skin in adult or 2-wk-old mice. Afferents were recorded from small filaments of either sural or saphenous nerves in an outbred mice strain or in the inbred Balb/c strain. On the basis of their receptive properties and conduction velocity, several receptor types could be distinguished. In adult animals (>6 wk old), 54% of the large myelinated fibers (Aβ, n = 83) showed rapidly adapting (RA) discharges to constant force stimuli and probably innervated hair follicles, whereas 46% displayed a slowly adapting (SA) response and probably innervated Merkel cells in touch domes. Among thin myelinated fibers (Aδ, n = 91), 34% were sensitive D hair receptors and 66% were high-threshold mechanoreceptors (AM fibers). Unmyelinated fibers had high mechanical thresholds and nociceptive functions. All receptor types had characteristic stimulus-response functions to suprathreshold force stimuli. Noxious heat stimuli (15-s ramp from 32 to 47°C measured at the corium side of the skin) excited 26% (5 of 19) of AM fibers with a threshold of 42.5 ± 1.4°C (mean ± SE) and an average discharge of 15.8 ± 9.7 action potentials and 41% (7 of 17) C fibers with a mean threshold of 37.6 ± 1.9°C and an average discharge of 22.0 ± 6.0 action potentials. Noxious cold stimuli activated 1 of 10 AM fibers and 3 of 10 C fibers. One of 10 C units responded to both heat and cold stimuli. All types of afferent fibers present in adult mice could readily be recognized in mice at postnatal day 14. However, fibers had reduced conduction velocities and the stimulus-response function to mechanical stimuli was more shallow in all fibers except for the D hairs. In juvenile mice, 22% of RA units also displayed an SA response at high stimulus intensities; these units were termed RA/SA units. We conclude that all types of cutaneous afferent fibers are already committed to their phenotype 2 wk after birth but undergo some maturation over the following weeks. This preparation has great potential for the study of transgenic mice with targeted mutations of genes that code factors that are involved in the specification of sensory neuron phenotypes.


1997 ◽  
Vol 77 (3) ◽  
pp. 1566-1580 ◽  
Author(s):  
X. Su ◽  
J. N. Sengupta ◽  
G. F. Gebhart

Su, X., J. N. Sengupta, and G. F. Gebhart. Effects of opioids on mechanosensitive pelvic nerve afferent fibers innervating the urinary bladder of the rat. J. Neurophysiol. 77: 1566–1580, 1997. A total of 443 pelvic nerve afferent fibers in the L6 dorsal root of the rat were identified by electrical stimulation of the pelvic nerve; 319 (72%) were myelinated Aδ fibers with a mean conduction velocity (CV) of 11.8 m/s and 124 (28%) were unmyelinated C fibers with mean CV of 1.9 m/s. Two hundred fifty-two fibers (57%) responded to noxious urinary bladder distension (UBD; 80 mmHg); 108 were C fibers (mean CV: 1.9 m/s) and 144 were Aδ fibers (mean CV: 8.2 m/s). Forty-nine UBD-sensitive fibers were further characterized; all gave monotonic increases in firing to increasing distending pressures. Thirty-six fibers (73%) had a low-threshold (LT) for response (mean: 6 mmHg) and 13 fibers (27%) had high-thresholds (HT) for response (mean: 32 mmHg). Responses of 15 fibers to graded UBD (11 LT and 4 HT) were tested before and after instillation of 0.5 ml of 30% xylenes ( n = 11) or 5% mustard oil ( n = 4) into the bladder. The mean resting activity of 13 fibers significantly increased, and 7 fibers exhibited sensitization of responses to graded UBD 30 min after xylenes or mustard oil instillation. All 4 HT fibers were sensitized; 3 of the 11 LT fibers were sensitized (i.e., gave increased responses to UBD). The effects of opioid receptor agonists were tested on responses to noxious UBD (80 mmHg). Cumulative intraaterial doses of μ-opioid receptor agonists (morphine, 8 mg/kg, and fentanyl, 300 μg/kg) and of δ-opioid receptor agonists (DPDPE, 300 μg/kg, and SNC-80, 300 μg/kg) did not affect responses to noxious UBD. In contrast, cumulative 16 mg/kg intraarterial doses of the κ-opioid receptor agonists U50,488H, U69,593 and U62,066 dose-dependently attenuated responses to noxious UBD. There were no differences in the dose-response relationships of these drugs on afferent fibers from untreated and xylenes- or mustard oil-treated urinary bladder. These results reveal that there is a greater proportion of UBD-sensitive fibers in the L6 dorsal root (57%) than in the S1 dorsal root of the rat (38%; a previous study). The attenuation of responses to UBD by κ, but not μ or δ opioid receptor agonists suggests a potential use for peripherally acting κ opioid receptor agonists in the control of urinary bladder pain.


2000 ◽  
Vol 84 (4) ◽  
pp. 1924-1933 ◽  
Author(s):  
V. K. Shea ◽  
R. Cai ◽  
B. Crepps ◽  
J. L. Mason ◽  
E. R. Perl

Much attention has been given to the pelvic nerve afferent innervation of the urinary bladder; however, reports differ considerably in descriptions of afferent receptor types, their conduction velocities, and their potential roles in bladder reflexes and sensation. The present study was undertaken to do a relatively unbiased sampling of bladder afferent fibers of the pelvic nerve in adult female rats. The search stimulus for units to be studied was electrical stimulation of both the bladder nerves and the pelvic nerve. Single-unit activity of 100 L6 dorsal root fibers, activated by both pelvic and bladder nerve stimulation, was analyzed. Sixty-five units had C-fiber and 35 units had Aδ-fiber conduction velocities. Receptive characteristics were established by direct mechanical stimulation, filling of the bladder with 0.9% NaCl at a physiological speed and by filling the bladder with solutions containing capsaicin, potassium, or turpentine oil. The majority (61) of these fibers were unambiguously excited by bladder filling with 0.9% NaCl and were classified as mechanoreceptors. All mechanoreceptors with receptive fields on the body of the bladder had low pressure thresholds (≤10 mmHg). Receptive fields of units with higher thresholds were near the ureterovesical junction, on the base of the bladder or could not be found. Neither thresholds nor suprathreshold responses could be related to conduction velocity. Bladder compliance and mechanoreceptor thresholds were influenced by the stage of the estrous cycle: both were lowest in proestrous rats and highest in metaestrous rats. Mechanoreceptors innervating the body of the bladder and the region near the ureterovesical junction showed two patterns of responsiveness to slow bladder filling. One group of units exhibited increasing activity with increasing pressure up to 40 mmHg, while the other group showed a peak in activity at pressures below 40 mmHg followed by a plateau or decrease in activity with increasing pressure. It is proposed that differences in stimulus transduction relate to the different response patterns. Thirty-nine units failed to respond to bladder filling. Eight of these were excited by intravesical potassium or capsaicin and were classified as chemoreceptors. The remaining 31 units were not excited by any stimulus tested. Chemoreceptors and unexcited units had both Aδ and C afferent fibers. We conclude that the pelvic nerve sensory innervation of the rat bladder is complex, may be sensitive to hormonal status, and that the properties of individual sensory receptors are not related in an obvious manner to the conduction velocity of their fibers.


2009 ◽  
Vol 297 (6) ◽  
pp. G1250-G1258 ◽  
Author(s):  
Pablo Rodolfo Brumovsky ◽  
Bin Feng ◽  
Linjing Xu ◽  
Carly Jane McCarthy ◽  
G. F. Gebhart

Studies in humans and rodents suggest that colon inflammation promotes urinary bladder hypersensitivity and, conversely, that cystitis contributes to colon hypersensitivity, events referred to as cross-organ sensitization. To investigate a potential peripheral mechanism, we examined whether cystitis alters the sensitivity of pelvic nerve colorectal afferents. Male C57BL/6 mice were treated with cyclophosphamide (CYP) or saline, and the mechanosensitive properties of single afferent fibers innervating the colorectum were studied with an in vitro preparation. In addition, mechanosensitive receptive endings were exposed to an inflammatory soup (IS) to study sensitization. Urinary bladder mechanosensitive afferents were also tested. We found that baseline responses of stretch-sensitive colorectal afferents did not differ between treatment groups. Whereas IS excited a proportion of colorectal afferents CYP treatment did not alter the magnitude of this response. However, the number of stretch-sensitive fibers excited by IS was increased relative to saline-treated mice. Responses to IS were not altered by CYP treatment, but the proportion of IS-responsive fibers was increased relative to saline-treated mice. In bladder, IS application increased responses of muscular afferents to stretch, although no differences were detected between saline- and CYP-treated mice. In contrast, their chemosensitivity to IS was decreased in the CYP-treated group. Histological examination revealed no changes in colorectum and modest edema and infiltration in the urinary bladder of CYP-treated mice. In conclusion, CYP treatment increased mechanical sensitivity of colorectal muscular afferents and increased the proportion of chemosensitive colorectal afferents. These data support a peripheral contribution to cross-organ sensitization of pelvic organs.


1989 ◽  
Vol 61 (6) ◽  
pp. 1121-1130 ◽  
Author(s):  
W. S. Ammons

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.


1988 ◽  
Vol 59 (1) ◽  
pp. 41-55 ◽  
Author(s):  
R. J. Traub ◽  
L. M. Mendell

1. Recordings were made from individual sensory neurons with an A-delta peripheral conduction velocity, either intrasomally in the L7 dorsal root ganglion, or extracellularly in Lissauer's Tract or in the dorsal root close to the root entry zone. The spinal projection of these afferents was assessed by their antidromic response to stimulation of the dorsal columns (DC) or Lissauer's Tract (LT) at the L5/L6 border. The adequate stimulus was also ascertained. 2. A-delta-fibers could be divided into two groups: high-threshold mechanoreceptors from either skin or muscle (HTMRs) and low-threshold mechanoreceptors (LTMs), primarily Down Hairs. A third group of cells recorded intrasomally had broad spikes with shoulders on the downstroke characteristic of A-delta-nociceptors and were so classified provisionally, although no adequate stimulus could be identified. HTMRs and broad spike cells projected either in DC or LT, but LTMs projected only in DC, never in LT. About one-quarter of both groups failed to project rostrally as far as L5/L6. 3. Cells with unmyelinated axons recorded intrasomally were found to supply either low-threshold or high-threshold mechanoreceptors. Unlike A-delta-cells, all these cells had broad spikes with shoulders on the downstroke. Proportionally fewer C-fibers than A-delta-fibers projected as far as one segment rostral from their root entry zone. Of those that did, axons supplying low-threshold mechanoreceptors projected only in DC, whereas those innervating high-threshold mechanoreceptors could project either through LT or DC. 4. A-delta-fibers supplying LTMs and HTMRs exhibited a similar reduced conduction velocity was reduced even further in the spinal cord but much more for HTMRs than for LTMs. For C-fibers the conduction velocity decrease was more substantial in the dorsal root for HTMRs than for LTMs. 5. These findings suggest that axons innervating different peripheral receptors exhibit characteristic cellular properties. They confirm that the primary afferent component of Lissauer's Tract is specialized as a “pain pathway” but also indicate that the dorsal columns may play some role in the transmission of nociceptive information.


2008 ◽  
Vol 100 (5) ◽  
pp. 2771-2783 ◽  
Author(s):  
Nevena Milenkovic ◽  
Christiane Wetzel ◽  
Rabih Moshourab ◽  
Gary R. Lewin

Here we have systematically characterized the stimulus response properties of mechanosensitive sensory fibers in the mouse saphenous nerve. We tested mechanoreceptors and nociceptors with defined displacement stimuli of varying amplitude and velocity. For each sensory afferent investigated we measured the mechanical latency, which is the delay between the onset of a ramp displacement and the first evoked spike, corrected for conduction delay. Mechanical latency plotted as a function of stimulus strength was very characteristic for each receptor type and was very short for rapidly adapting mechanoreceptors (<11 ms) but very long in myelinated and unmyelinated nociceptors (49–114 ms). Increasing the stimulus speed decreased mechanical latency in all receptor types with the notable exception of C-fiber nociceptors, in which mean mechanical latency was not reduced ≲100 ms, even with very fast ramp stimuli (2,945 μm/s). We examined stimulus response functions and mechanical latency at two different temperatures (24 and 32°C) and found that stimulus response properties of almost all mechanoreceptors were not altered in this range. A notable exception to this rule was found for C-fibers in which mechanical latency was substantially increased and stimulus response functions decreased at lower temperatures. We calculated Q10 values for mechanical latency in C-fibers to be 5.1; in contrast, the Q10 value for conduction velocity for the same fibers was 1.4. Finally, we examined the effects of short-term inflammation (2–6 h) induced by carrageenan on nociceptor and mechanoreceptor sensitivity. We did not detect robust changes in mechanical latency or stimulus response functions after inflammation that might have reflected mechanical sensitization under the conditions tested.


1989 ◽  
Vol 61 (3) ◽  
pp. 573-588 ◽  
Author(s):  
T. J. Brennan ◽  
U. T. Oh ◽  
S. F. Hobbs ◽  
D. W. Garrison ◽  
R. D. Foreman

1. Extracellular recordings were made from 41 spinothalamic tract (STT) neurons on the left side of the T2-T5 spinal segments of 20 monkeys (Macaca fascicularis) anesthetized with alpha-chloralose. Manipulation of the left triceps-chest region and electrical stimulation of cardiopulmonary sympathetic afferent fibers excited these cells. 2. Isotonic urinary bladder distensions (UBD) to pressures between 20 and 80 cmH2O reduced the spontaneous activity in 33 of 41 cells. Cell activity was significantly reduced by UBD at 20 cmH2O. Distensions to 40, 60, and 80 cmH2O produced progressively greater reductions in spontaneous discharge. Activity was decreased throughout distension in 29 cells (tonic inhibition) and at the onset of distension in 3 neurons (phasic inhibition). In one cell, inhibition followed a brief excitation at the onset of distension (phasic excitation-tonic inhibition). Spontaneous bladder contractions also inhibited STT cell activity. 3. Inhibition by UBD was observed in STT cells characterized as wide dynamic range, high threshold, and high threshold inhibitory. No correlation existed between cell type or laminar location and inhibition by urinary bladder distension. Cells excited by cardiopulmonary sympathetic afferent A delta- and C-fibers had a significantly greater tendency to be inhibited by UBD (17 of 18) than cells activated by A delta- but not C-fibers (13 of 20). 4. Urinary bladder distension and pinch of the hindlimbs also reduced activity of STT cells excited by input from cardiopulmonary sympathetic afferents and from the proximal forelimb. 5. Urinary bladder distension to 40, 60, or 80 cmH2O produced a greater absolute but smaller relative reduction in the firing frequency of STT cells as spontaneous activity increased. Thus the magnitude of this inhibitory effect may depend on whether the inhibitory effect is measured as an absolute or relative change in cell activity. 6. Convergent inhibitory input from somatic regions also was observed. Noxious pinch of the hamstring region of the right hindlimb decreased activity in 32 of 39 cells. Left hindlimb pinch inhibited 21 of 38 cells, and 15 of 29 cells were inhibited by right triceps pinch. 7. Convergent inhibitory input from the hamstring region of the hindlimbs and from the urinary bladder to upper thoracic STT cells may be important for coding the intensity and location of noxious visceral and somatic stimuli and for organizing the appropriate sequence of motor responses when multiple noxious stimuli are present.


1999 ◽  
Vol 277 (4) ◽  
pp. R1002-R1012 ◽  
Author(s):  
Karl B. Thor ◽  
Mark A. Muhlhauser

Irritation of the urinary bladder causes activation of normally “silent” nociceptive primary afferent fibers. In the present study, it is reported that irritation of the urinary bladder or urethra with infusion of 0.5% acetic acid robustly activates motoneurons that innervate the striated muscle of the external anal sphincter via spinal reflex mechanisms. The activation of anal motoneurons following irritation of the bladder and urethra are termed vesicoanal and urethroanal reflexes, respectively. The reflexes can be mimicked by acute application of capsaicin to the bladder and urethra, and they show desensitization following prolonged topical application of capsaicin or following chronic systemic pretreatment with capsaicin. The reflexes can be demonstrated in chronic spinal cord-transected animals, indicating that the reflex pathways are organized within the spinal cord. The urethroanal reflex is also physiologically activated by urethral distension and/or increases in intraluminal pressure. In addition to activation of anal sphincter activity, slight distension, pressure increases, or instillation of 0.5% acetic acid into the urethra inhibited bladder contractions through activation of an inhibitory urethrovesical reflex. These reflexes are discussed in terms of clinical characteristics of urethritis and prostatitis. Anecdotally, it was discovered that the bladder can buffer acetic acid.


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