Distribution of capsaicin-sensitive urinary bladder afferents in the rat spinal cord (original) (raw)

Desensitization follows excitation of bladder primary afferents by intravesical capsaicin, as shown by c- fos activation in the rat spinal cord

Pain, 1996

Activation of the protooncogene c-fos at spinal cord segments T12-L2 and L5-S1 was used to study the effects of topical administration of capsaicin on bladder primary afferents coursing in the hypogastric (HGN) or pelvic (PN) nerves of adult rats. Two hours after capsaicin instillation in the bladder numerous Fos cells occurred in lamina I at T12-L2 and in lamina 1, intermediolateral gray matter (ILG) and dorsal commissure (DCM) at L5-S1. Twenty-four hours later, the Fos immunoreaction had disappeared from the spinal cord. At this time, instillation of 1% acetic acid into the bladder of capsaicin-treated rats induced considerably fewer Fos cells than in animals that had been instilled only with the vehicle solution for capsaicin. The difference in the average number of Fos cells was statistically significant in lamina I, ILG and DCM at L5-S1 but not in lamina I at T12-L2. Thus, intravesical capsaicin at the doses used excites bladder primary afferents coursing in the HGN and PN, but only desensitizes those coursing in the PN. It is suggested that this may depend on the differential occurrence of capsaicin receptors in the two nerves.

Species-related differences in the capsaicin-sensitive innervation of the rat and guinea-pig ureter

Naunyn-Schmiedeberg's Archives of Pharmacology, 1988

1. Comparison of the tissue content of calcitonin gene-related peptide (CGRP)-immunoreactivity (IR) and tachykinin (TK)-IR in the rat and guinea-pig ureter showed that in the rat tissue levels of CGRP-IR were 33-fold higher than those of TK-IR. In the guinea-pig ureter, both peptides were present in nearly the same concentration. 2. The invitro release of neuropeptides from guinea-pig and rat ureters was investigated using capsaicin as a stimulus for afferent neurons. Capsaicin induced the simultaneous release of CGRP-IR and TK-IR from the guinea-pig ureter while in the rat only the release of CGRP-IR was detectable. 3. It is known that TK potently stimulate and CGRP inhibits ureteric smooth muscle contractions. When the effect of capsaicin on ureteric motility was investigated in guinea-pig and rat, only in the guinea-pig ureter a stimulatory action ascribable to capsaicin-induced TK release was observed thus supplementing the results obtained by radioimmunoassay. 4. The results show that considerable species differences exist concerning the ratio of CGRP and TK which is stored and released from ureteric afferent nerve terminals. As a consequence, different functional responses are obtained in both species upon stimulation of these neurons by capsaicin. In the rat ureter, the capsaicin-sensitive innervation seems to be only inhibitory while in the guinea-pig stimulatory and inhibitory transmitters are released. The physiological significance of the simultaneous release of transmitters with opposing effects needs further investigation.

The role of capsaicin-sensitive afferent fibers in the lower urinary tract dysfunction induced by chronic spinal cord injury in rats

Experimental Neurology, 2004

The role of capsaicin-sensitive afferents in neurogenic voiding dysfunction was studied in chronic spinal cord injured rats (SCI). Cystometry and external urethral sphincter (EUS) electromyography were performed on 2 consecutive days after induction of urethane anesthesia in SCI rats 6 -8 weeks after spinal cord injury. SCI rats exhibited voiding abnormalities including: non-voiding contractions (NVCs) before micturition, increased volume threshold (VT) for initiating voiding, increased amplitude and duration of voiding contractions, decreased voiding efficiency, increased residual urine, and changes in the pattern of the EUS-EMG. In SCI rats, the EUS electromyogram (EUS-EMG) consisted of more prominent tonic activity, shorter periods of bursting activity, and a reduction in the ratio of silent to active periods during bursting. These changes were more prominent during deeper levels of anesthesia on day 1. Capsaicin (125 mg/kg, s.c., 4 days before urodynamic examination) reduced VT and the number of NVCs, decreased the amplitude and duration of voiding contractions, partially normalized the pattern of EUS-EMG activity, and improved the voiding efficiency on day 1 after induction of anesthesia but not on day 2. Capsaicin treatment increased the percentage of animals (from 55% to 80%) that voided on day 1. The results indicate that capsaicin-sensitive C-fiber bladder afferents are not essential for reflex micturition in SCI rats. However, these afferents do contribute to overactivity of the bladder and detrusor sphincter dyssynergia in deeply anesthetized SCI rats.

Neurochemical evidence for the activation of the ‘efferent’ function of capsaicin-sensitive nerves by lowering of the pH in the guinea-pig urinary bladder

Neuroscience Letters, 1990

Proton; Calcitonin gene-related peptide; Sensory neuron; Capsaicin Lowering of the pH of the superfusion solution (physiological phosphate buffers derived from normal Krebs solution) of mucosa-free muscle strips of the guinea-pig urinary bladder from 7.4 to 6 or 5, produced a marked increase of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) outflow (total evoked release being 1677 +_ 287 fmol/g/35 min and 5283 + 484 fmol/g/35 min, respectively). The increase in CGRP-LI outflow evoked by exposure to pH 5 was abolished in strips pre-exposed to capsaicin (I0/IM for 20 min), and was reduced by approximately 80% when superfusion was performed with Ca 2+free media. After application of pH 5 solution, capsaicin (10 /tM) evoked a CGRP-LI release that amounted to 21% of controls. It is concluded that lowering of the pH induces a Ca2+-dependent release of CGRP-L I from capsaicin-sensitive nerves in the guinea-pig urinary bladder.

The motor effect of the capsaicin-sensitive inhibitory innervation of the rat ureter

European Journal of Pharmacology, 1986

Neurokinins activate a series of tetrodotoxin (TTX)-insensitive rhythmic contractions of the rat isolated ureter. Field stimulation or capsaicin (1-3 #M) produced a transient inhibition of neurokinin-activated ureteral motility in preparations from control but not from capsaicin-pretreated (50 mg/kg s.c.) rats. The inhibitory action of field stimulation but not that of capsaicin was prevented by TTX. It is concluded that a capsaicin-sensitive inhibitory innervation exists in the rat ureter. Ureteral motility Capsaicin Neurokinins Tetrodotoxin

Afferent nerve distribution in the bladder wall of young mice

2010

In the urinary bladder, the cholinergic innervation is an essential component of a motor-sensory mechanism. Recent studies show that anti-muscarinics may decrease the afferent activity of sensory nerves [1]. It is therefore important to investigate were sensory nerves in the bladder are located. This study describes the different localizations of afferent nerves throughout the bladder wall in normal mice.

Regional differences in the distribution of capsaicin-sensitive target-identified adult rat dorsal root ganglion neurons

Neuroscience Letters, 1992

A retrograde labelling technique combined with a cobalt uptake assay in cultured adult rat dorsal root ganglion (DRG) neurons were applied to study the distribution of capsaicin sensitivity in relation to different peripheral targets. This study shows that there are regional differences between skin, skeletal muscle and urinary bladder; 20 30% of skin afferents, 40% of muscle afferents and 60% of bladder afferents were found to be capsaicin-senditive. This may reflect differences in the proportion of chemosensitive afferents innervating different peripheral tissues.

Peptide immunoreactivity and ultrastructure of rat urinary bladder nerve fibers after topical desensitization by capsaicin or resiniferatoxin

Autonomic Neuroscience-basic & Clinical, 2000

In the present study the decrease of neuropeptide containing nerve fibers and the increase in the volume threshold to reflex micturition occurring in the rat bladder after intravesical application of capsaicin or resiniferatoxin were compared. The ultrastructure of bladder terminal axons was evaluated at the moment of maximal peptide depletion and compared to that of nerve fibers after systemic capsaicin application. Adult Wistar rats were treated intravesically for 30 min with 0.5 ml of 100 nM RTX, 1 mM capsaicin or 30% ethanol in saline, the vehicle solution. Twenty-four hours and 1, 2, 3, 4 and 8 weeks later the bladders were immunostained for CGRP, SP, VIP and NPY. Cystomanometric studies were performed 24 h and 1, 8, and 12 weeks after vanilloid instillation. Twenty-four hours after systemic capsaicin or intravesical capsaicin or RTX, bladders were prepared for electron microscopic (EM) observation. Intravesical capsaicin or RTX decreased, in a similar way, the number of CGRP and SP-IR (immunoreactive) fibers coursing in the muscular layer and the mucosa. IR fibers amounted to less than 20% of controls at 24 h and returned to normal levels in the eighth week. At the EM level, bladders treated with topical vanilloids did not show morphological changes in terminal axons coursing in the mucosa. In contrast, bladders from animals treated systemically with capsaicin contained numerous grossly degenerated nerve fibers. VIP and NPY-IR fibers were not affected by the treatment. Cystometrograms showed an increase of the volume threshold to reflex micturition that started at 24 h and disappeared at 12 weeks. We conclude that intravesical capsaicin or RTX were equally effective in terms of reducing the number of SP and CGRP-IR fibers and increasing the volume threshold for reflex micturition. Both changes were transient and were not associated with ultrastructural changes of the bladder nerve fibers, excluding terminal axon degeneration as the main mechanism of action of intravesical vanilloids.

Bladder distension and activation of the efferent function of sensory fibres: similarities with the effect of capsaicin

British Journal of Pharmacology, 1998

1 The eects of the tachykinin NK 2 receptor antagonist MEN 11420 (100 nmol kg 71 , i.v.) and isoprenaline (400 nmol kg 71 , i.v.) were compared in a model of distension-induced bladder activity in isovolumetric conditions. MEN 11420 induced a relaxation of the basal tone of the urinary bladder that was dependent on the volume of the viscus: the eect was absent at low volumes (0.2 and 0.5 ml) and it was maximal at high volumes of distension (1 and 2 ml), approaching about 60% of the isoprenalineinduced relaxation. The relaxant eect of isoprenaline was always evident at all volumes of distension. 2 Tetrodotoxin (1 ± 100 mM, intravesically applied) abolished distension-evoked micturition contractions, but did not prevent the relaxant eect of MEN 11420-or isoprenaline on the bladder tone.