Characterization of a spinal, urine storage reflex, inhibitory center and its regulation by 5-HT_1A receptors in female cats

Abstract

Urine storage is facilitated by somatic (pudendal nerve) and sympathetic [hypogastric nerve (HgN)] reflexes to the urethral rhabdosphincter (URS) and urethral smooth muscle, respectively, initiated by primary afferent fibers in the pelvic nerve (PelN). Inhibition of storage reflexes is required for normal voiding. This study characterizes a urine storage reflex inhibitory network that can be activated by PelN afferent fibers concurrently with the reflexes themselves. Electrical stimulation of PelN produced evoked potentials recorded by URS EMG electrodes (10-ms latency) or HgN electrodes (60-ms latency) in chloralose-anesthetized cats. When a second (i.e., paired) pulse of the same stimulus intensity was applied to the PelN 50-500 ms after the first, the reflexes evoked by the second stimulus were inhibited. The inhibition was maximal at paired-pulse intervals of 50-100 ms and remained after acute spinal transection at T10, confirming that the inhibitory center is located in the spinal cord. The 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tertralin (8-OH-DPAT; 3-300 mug/kg iv) consistently reduced the paired-pulse inhibition from 20% to 60% of control in spinal-intact animals but had no effect in acute spinal animals (i.e., supraspinal site of action). N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-2-pyridinylcyclohexanecarboxamide maleate (300 mug/kg iv) completely reversed 8-OH-DPAT's effects. The PelN-HgN reflex paired-pulse inhibition was not affected by 8-OH-DPAT. These results indicate the presence of a spinal, urine storage reflex, inhibitory center (SUSRIC) that is activated within 50 ms after activation of the reflexes themselves. SUSRIC is inhibited (disfacilitated) by supraspinal 5-HT(1A) receptors.

Regulatory Effects of 5-Hydroxytryptamine Receptors on Voiding Function

“…However, central 5-HT 1A function in bladder and sphincter activity is still unclear because its role appears to be strongly species dependent. In cats, 5-HT 1A activation results in inhibition of parasympathetic excitatory input to the urinary bladder and facilitation of the external urethral sphincter (EUS) EMG activity [53,54].…”

“…The increase in sphincter activity by 5-HT 1A is achieved by a process of disinhibition: the spinal, urine storage reflex, inhibitory center (SUSRIC) inhibits the urethral sphincter motor nucleus, and SUSRIC activity is inhibited by supraspinal 5-HT 1A receptors [53]. In contrast to that in cats, central 5-HT 1A activation in rats causes enhancement of reflex activity in the bladder and sphincter, whereas its blockade reduces these reflex activities [55,56].…”

Spinal interneurons and micturition reflexes: focus on “Characterization of a spinal, urine storage reflex, inhibitory center and its regulation by 5-HT1A receptors in female cats”

“…Importantly, the observed inhibition was still observed after acute spinal cord transection at T10 confirming the spinal cord location of the inhibitory center, which the authors have termed a spinal, urine storage reflex, inhibitory center (SUSRIC). As detailed in the paper (14), additional data from the study suggest two separate SUSRICs, one being involved in the sympathetic storage reflex and a separate one being involved in the somatic urine storage reflex. Under normal conditions, the authors suggest that a SUSRIC may function as a redundant or additional system to promote urethral relaxation (14).…”

“…Electrical stimulation of pelvic nerves elicited evoked potentials in electromyogram electrodes placed in the urethral sphincter/rhabdosphincter or in hypogastric nerve electrodes in anesthetized cats. Using a conditioning test paired-pulse paradigm, Karicheti et al (14) observed that the reflexes evoked by the second stimulus were inhibited. Importantly, the observed inhibition was still observed after acute spinal cord transection at T10 confirming the spinal cord location of the inhibitory center, which the authors have termed a spinal, urine storage reflex, inhibitory center (SUSRIC).…”

New Insights into the Pathophysiology of Detrusor-Sphincter Dyssynergia

“…That it is also apparent in SCT cats adds this species to the list of those that possess a spinal PFPAPG. Whether this neural oscillator is related to the recently described "spinal, urine storage reflex, inhibitory center" in the cat [37] is not currently known.…”