Abstract
Reflexes, that involve the spinobulbospinal pathway control both storage and voiding of urine. The periaqueductal gray matter (PAG), a pontine structure is part of the micturition pathway. Alteration in this pathway could lead to micturition disorders and urinary incontinence, such as the overactive bladder symptom complex (OABS). Although different therapeutic options exist for the management of OABS, these are either not effective in all patients. Part of the pathology of OABS is faulty sensory signaling about the filling status of the urinary bladder, which results in aberrant efferent signaling leading to overt detrusor contractions and the sensation of urgency and frequent voiding. In order to identify novel targets for therapy (i.e., structures in the central nervous system) and explore novel treatment modalities such as neuromodulation, we aimed at investigating which areas in the central nervous system are functionally activated upon sensory afferent stimulation of the bladder. Hence, we designed a robust protocol with multiple readout parameters including immunohistological and behavioral parameters during electrical stimulation of the rat urinary bladder. Bladder stimulation induced by electrical stimulation, below the voiding threshold, influences neural activity in: (1) the caudal ventrolateral PAG, close to the aqueduct; (2) the pontine micturition center and locus coeruleus; and (3) the superficial layers of the dorsal horn, sacral parasympathetic nucleus and central canal region of the spinal cord. In stimulated animals, a higher voiding frequency was observed but was not accompanied by increase in anxiety level and locomotor deficits. Taken together, this work establishes a critical role for the vlPAG in the processing of sensory information from the urinary bladder and urges future studies to investigate the potential of neuromodulatory approaches for urological diseases.
Highlights
Overactive bladder symptom complex (OABS) is one of the most frequently encountered urological disorders
The idea is derived from the principle of transurethral intravesical electrostimulation (IVES), which has been used to initiate non-voiding contractions, which result in the depolarization of afferent sensory nerve fibers and subsequently a strong centrally-induced detrusor contraction (Madersbacher, 1990; Ebner et al, 1992; Buyle et al, 1998; Jiang, 1998; Streng et al, 2006)
The response to electrical stimulation of the bladder with a current intensity of 2 mA was characterized by a rise in pressure to reach a plateau and a decrease towards the baseline (Figure 1A)
Summary
Overactive bladder symptom complex (OABS) is one of the most frequently encountered urological disorders. The complex is defined as a medical condition encompassing urgency, increased daytime frequency, Sensory Brain-Bladder Connection nocturia and urgency urinary incontinence (i.e., involuntary loss of urine associated with urgency) either isolated or in any combination (Abrams et al, 2003). This is not considered as a severe health condition, it has a significant impact on personal autonomy, self-esteem, quality of life, quality of sleep and mental health and it creates an enormous economic burden (Irwin et al, 2006; Onukwugha et al, 2009). Knowledge about structures within the central nervous system involved in the micturition pathway can aid in developing novel rationallydesigned treatment modalities and can help to identify patients, which are good candidates for specific lines of treatment
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