Post-Stimulation Inhibitory Effect on Reflex Bladder Activity Induced by Activation of Somatic Afferent Nerves in the Foot

Activation of TRP channels expressed in urinary bladder afferent nerves and urothelium releases neurotransmitters that influence bladder function. Experiments were undertaken to examine the mechanisms underlying effects of TRPA1 (allyl isothiocyanate, AITC), TRPV1 (capsaicin, CAPS), and TRPC (oleoyl-2-acetyl-sn-glycerol, OAG) agonists on guinea pig bladder activity. Effects of these agonists were compared with effects of nitro-oleic acid (OA-NO2), an electrophilic nitro-fatty acid, known to activate TRPV1, TRPA1 or TRPC channels in sensory neurons. AITC (100 μM) increased (231%) area of spontaneous bladder contractions (SBCs) an effect reduced by a TRPA1 antagonist (HC3-03001, HC3, 10 μM) and reversed to inhibition by indomethacin (INDO, 500 nM) a cyclooxygenase inhibitor. The post-INDO inhibitory effect of AITC was mimicked (39% depression) by calcitonin gene-related peptide (CGRP, 100 nM) and blocked by a CGRP antagonist (BIBN, 25 μM). CAPS (1 μM) suppressed SBCs by 30% in 81% of strips, an effect blocked by a TRPV1 antagonist (diarylpiperazine, 1 μM) or BIBN. SBCs were suppressed by OA-NO2 (30 μM, 21% in 77% of strips) or by OAG (50 μM, 30%) an effect blocked by BIBN. OA-NO2 effects were not altered by HC3 or diarylpiperazine. OA-NO2 also induced excitation in 23% of bladder strips. These observations raise the possibility that guinea pig bladder is innervated by at least two types of afferent nerves: [1] Type A express TRPA1 receptors that induce the release of prostaglandins and excite the detrusor, [2] Type B express TRPV1, TRPA1 and TRPC receptors and release CGRP that inhibits the detrusor.

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The long-lasting post-stimulation inhibitory effects of bladder activity induced by posterior tibial nerve stimulation in unanesthetized rats

Scientific Reports ◽

10.1038/s41598-020-76987-2 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Eunkyoung Park ◽

Jae-Woong Lee ◽

Taekyung Kim ◽

Minhee Kang ◽

Baek Hwan Cho ◽

...

Keyword(s):

Nerve Stimulation ◽

Tibial Nerve ◽

Inhibitory Effect ◽

Inhibitory Response ◽

Inhibitory Effects ◽

Tibial Nerve Stimulation ◽

Neurophysiological Mechanisms ◽

Bladder Activity ◽

Important Evidence

AbstractTibial nerve stimulation (TNS) is one of the neuromodulation methods used to treat an overactive bladder (OAB). However, the treatment mechanism is not accurately understood owing to significant differences in the results obtained from animal and clinical studies. Thus, this study was aimed to confirm the response of bladder activity to the different stimulation frequencies and to observe the duration of prolonged post-stimulation inhibitory effects following TNS. This study used unanesthetized rats to provide a closer approximation of the clinical setting and evaluated the changes in bladder activity in response to 30 min of TNS at different frequencies. Moreover, we observed the long-term changes of post-stimulation inhibitory effects. Our results showed that bladder response was immediately inhibited after 30 min of 10 Hz TNS, whereas it was excited at 50 Hz TNS. We also used the implantable stimulator to observe a change in duration of the prolonged post-stimulation inhibitory effects of the TNS and found large discrepancies in the time that the inhibitory effect lasted after stimulation between individual animals. This study provides important evidence that can be used to understand the neurophysiological mechanisms underlying the bladder inhibitory response induced by TNS as well as the long-lasting prolonged post-stimulation effect.

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Involvement of 5-HT3 receptors in pudendal inhibition of bladder overactivity in cats

AJP Renal Physiology ◽

10.1152/ajprenal.00105.2013 ◽

2013 ◽

Vol 305 (5) ◽

pp. F663-F671 ◽

Cited By ~ 22

Author(s):

Zeyad Schwen ◽

Yosuke Matsuta ◽

Bing Shen ◽

Jicheng Wang ◽

James R. Roppolo ◽

...

Keyword(s):

High Intensity ◽

Bladder Capacity ◽

Saline Control ◽

Low Intensity ◽

Afferent Nerves ◽

Normal Bladder ◽

Pudendal Neuromodulation ◽

Bladder Symptoms ◽

Bladder Activity

In the present study, the role of 5-HT3 receptors in pudendal neuromodulation of bladder activity and its interaction with opioid receptors were investigated in anesthetized cats. The bladder was distended with either saline to induce normal bladder activity or with 0.25% acetic acid (AA) to induce bladder overactivity. Pudendal afferent nerves were activated by 5-Hz stimulation at multiples of the threshold (T) intensity for the induction of anal twitching. AA irritation significantly reduced bladder capacity to 16.5 ± 3.3% of saline control capacity, whereas pudendal nerve stimulation (PNS) at 1.5–2 and 3–4 T restored the capacity to 82.0 ± 12% ( P = 0.0001) and 98.6 ± 15% ( P < 0.0001), respectively. Cumulative doses (1–3 mg/kg iv) of ondansetron, a 5-HT3 receptor antagonist, eliminated low-intensity (1.5–2 T) PNS inhibition and reduced high-intensity (3–4 T) PNS inhibition of bladder overactivity. During saline distention, PNS at 1.5–2 and 3–4 T significantly increased bladder capacity to 173.2 ± 26.4% ( P = 0.036) and 193.2 ± 22.5% ( P = 0.008), respectively, of saline control capacity, but ondansetron (0.003–3 mg/kg iv) did not alter PNS inhibition. Ondansetron (0.1–3 mg/kg) also significantly ( P < 0.05) increased control bladder capacity (50–200%) during either AA irritation or saline distention. In both conditions, the effects of low- and high-intensity PNS were not significantly different. After ondansetron (3 mg/kg) treatment, naloxone (1 mg/kg iv) significantly ( P < 0.05) decreased control bladder capacity (40–70%) during either AA irritation or saline distention but failed to affect PNS inhibition. This study revealed that activation of 5-HT3 receptors has a role in PNS inhibition of bladder overactivity. It also indicated that 5-HT3 receptor antagonists might be useful for the treatment of overactive bladder symptoms.

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Inhibitory effect of amiloride and gadolinium on fine afferent nerves in the rat knee: evidence of mechanogated ion channels in joints

Experimental Brain Research ◽

10.1007/s00221-005-0040-z ◽

2005 ◽

Vol 167 (1) ◽

pp. 114-118 ◽

Cited By ~ 21

Author(s):

Bernd Heppelmann ◽

Jason J. McDougall

Keyword(s):

Ion Channels ◽

Inhibitory Effect ◽

Afferent Nerves

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Inhibitory effects on intake of cholecystokinin-8 and cholecystokinin-33 in rats with hepatic proper or common hepatic branch vagal innervation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00062.2005 ◽

2005 ◽

Vol 289 (2) ◽

pp. R456-R462 ◽

Cited By ~ 23

Author(s):

S. Eisen ◽

R. J. Phillips ◽

N. Geary ◽

E. A. Baronowsky ◽

T. L. Powley ◽

...

Keyword(s):

Intraperitoneal Administration ◽

Inhibitory Effect ◽

Inhibitory Interaction ◽

Afferent Nerves ◽

Afferent Fibers ◽

Vagal Nerves ◽

Vagal Innervation ◽

Afferent Vagal ◽

Vagal Afferent ◽

Hepatic Branch

The relative potencies of cholecystokinin (CCK)-8 and CCK-33 for decreasing meal size depend on the route of administration. Inhibitory potencies are equal after intraperitoneal administration, but CCK-33 is significantly more potent after intraportal administration. This suggests that CCK-33 is a more effective stimulant of hepatic afferent vagal nerves than is CCK-8. To investigate this possibility, we administered both peptides intraperitoneally in rats with abdominal vagotomies that spared only the hepatic proper vagal nerves (H) and in rats with abdominal vagotomies that spared the common hepatic branch that contains the fibers of the hepatic proper and gastroduodenal nerves (HGD). The vagal afferent innervation in H and HGD rats was verified with a wheat germ agglutinin-horseradish tracer strategy. Intraperitoneal administration of CCK-33 decreased 30-min intake of 10% sucrose in H rats as much as in sham rats, but CCK-8 decreased intake significantly less in H rats than in sham rats. The larger inhibitory effect of CCK-33 than of CCK-8 in H rats is consistent with the hypothesis that CCK-33 is a more effective stimulant of the hepatic proper vagal afferent nerves than CCK-8. In contrast to the results in H rats, the inhibitory potencies of both peptides were significantly and equivalently reduced in HGD rats compared with sham rats. This suggests that there is an inhibitory interaction between the stimulation of the gastroduodenal and hepatic proper afferent fibers by CCK-33.

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Neural pathways involved in sacral neuromodulation of reflex bladder activity in cats

AJP Renal Physiology ◽

10.1152/ajprenal.00334.2012 ◽

2013 ◽

Vol 304 (6) ◽

pp. F710-F717 ◽

Cited By ~ 43

Author(s):

Fan Zhang ◽

Shouguo Zhao ◽

Bing Shen ◽

Jicheng Wang ◽

Dwight E. Nelson ◽

...

Keyword(s):

Central Nervous System ◽

Sacral Neuromodulation ◽

Bladder Capacity ◽

Inhibitory Effect ◽

Ventral Root ◽

Neural Pathways ◽

Descending Pathways ◽

The Central Nervous System ◽

Bladder Activity ◽

Stimulation Of

This study examined the mechanisms underlying the effects of sacral neuromodulation on reflex bladder activity in chloralose-anesthetized cats. Bladder activity was recorded during cystometrograms (CMGs) or under isovolumetric conditions. An S1–S3 dorsal (DRT) or ventral root (VRT) was electrically stimulated at a range of frequencies (1–30 Hz) and at intensities relative to threshold (0.25–2T) for evoking anal/toe twitches. Stimulation of DRTs but not VRTs at 1T intensity and frequencies of 1–30 Hz inhibited isovolumetric rhythmic bladder contractions. A 5-Hz DRT stimulation during CMGs was optimal for increasing ( P < 0.05) bladder capacity (BC), but stimulation at 15 and 30 Hz was ineffective. Stimulation of the S1 DRT was more effective (increases BC to 144% and 164% of control at 1T and 2T, respectively) than S2 DRT stimulation (increases BC to 132% and 150% of control). Bilateral transection of the hypogastric or pudendal nerves did not change the inhibitory effect induced by S1 DRT stimulation. Repeated stimulation of S1 and S2 DRTs during multiple CMGs elicited a significant ( P < 0.05) increase in BC (to 155 ± 11% of control) that persisted after termination of the stimulation. These results in cats suggest that the inhibition of reflex bladder activity by sacral neuromodulation occurs primarily in the central nervous system by inhibiting the ascending or descending pathways of the spinobulbospinal micturition reflex.

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Prolonged poststimulation inhibition of bladder activity induced by tibial nerve stimulation in cats

AJP Renal Physiology ◽

10.1152/ajprenal.00526.2010 ◽

2011 ◽

Vol 300 (2) ◽

pp. F385-F392 ◽

Cited By ~ 53

Author(s):

Changfeng Tai ◽

Bing Shen ◽

Mang Chen ◽

Jicheng Wang ◽

James R. Roppolo ◽

...

Keyword(s):

Spinal Cord ◽

Short Duration ◽

Nerve Stimulation ◽

Clinical Observation ◽

Tibial Nerve ◽

Bladder Capacity ◽

Inhibitory Effect ◽

Tibial Nerve Stimulation ◽

Bladder Symptoms ◽

Bladder Activity

Inhibition of bladder activity by tibial nerve stimulation was investigated in α-chloralose-anesthetized cats with an intact spinal cord. Short-duration (3–5 min) tibial nerve stimulation at both low (5 Hz) and high (30 Hz) frequencies applied repeatedly during rhythmic isovolumetric bladder contractions was effective in inhibiting reflex bladder activity. Both frequencies of stimulation were also effective in inducing inhibition that persisted after the termination of the stimulation. The poststimulation inhibitory effect induced by the short-duration stimulation significantly increased bladder capacity to 181.6 ± 24.36% of the control capacity measured before applying the stimulation. Thirty-minute continuous stimulation induced prolonged poststimulation inhibition of bladder activity, which lasted for more than 2 h and significantly increased bladder capacity to 161.1 ± 2.9% of the control capacity. During the poststimulation periods, 5-Hz stimulation applied during the cystometrogram elicited a further increase (∼30% on average) in bladder capacity, but 30-Hz stimulation was ineffective. These results in cats support the clinical observation that tibial nerve neuromodulation induces a long-lasting poststimulation inhibitory effect that is useful in treating overactive bladder symptoms.

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