Rostral Ventral Medulla Modulation of the Visceromotor Reflex Evoked by Urinary Bladder Distension in Female Rats

Randich, Alan; Mebane, Hannah; DeBerry, Jennifer J.; Ness, Timothy J.

doi:10.1016/j.jpain.2008.05.011

Cited by 25 publications

(23 citation statements)

References 27 publications

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“…The bidirectional firing properties observed following bladder distension align well with the three classical RVM cell types: on-cells which fire immediately prior to nociceptive cues, off-cells which are inhibited prior to nociceptive instances, and neutral cells that do not exhibit activity changes in during nociception. Electrical stimulation of the RVM induced both inhibition and, less frequently, facilitation of UBD-evoked pain-like responses, once again echoing the nociceptive dichotomy demonstrated by on- and off-cells 36 . The relative activity of these two RVM projection neuron classes likely determines whether bladder pain is increased or decreased by directly modulating activity in primary sensory afferents, including those arising from the bladder base and body, second and third order neurons, and interneurons within the dorsal horn 37 .…”

Section: Resultsmentioning

confidence: 72%

Urine Trouble: Alterations in Brain Function Associated with Bladder Pain

Sadler

Kolber

2016

Journal of Urology

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Purpose Chronic bladder pain is a debilitating condition often accompanied by alterations in affective and autonomic function. Many of the symptoms associated with chronic bladder pain are mediated by the central nervous system. In this review, data from preclinical animal models and human neuroimaging studies were analyzed and a theoretical supraspinal bladder pain network was generated. Materials and Methods A comprehensive literature review was performed using PubMed and Google Scholar. Relevant reviews, original research articles, and their cited references were summarized then organized on a neuroanatomical basis. Results The following brain loci are the most predominant in the bladder pain literature: thalamus, parabrachial nucleus, cerebral cortex, amygdala, hypothalamus, periaqueductal gray, and rostral ventromedial medulla. This review highlights each of these regions, discussing the molecular and physiological changes that occur in each during the context of bladder pain. Conclusions A complex network of brain loci is involved in bladder pain modulation. Studying these brain regions and the changes they undergo during the transition from acute to chronic bladder pain will provide novel therapeutic strategies for those suffering from chronic bladder pain diseases such as interstitial cystitis/bladder pain syndrome (IC/BPS) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

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Section: Resultsmentioning

confidence: 72%

Urine Trouble: Alterations in Brain Function Associated with Bladder Pain

Sadler

Kolber

2016

Journal of Urology

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“…alters responses to innocuous (10-30 mmHg), noxious (30-60 mmHg), and supra-physiological (60-80 mmHg) distending pressures. Bladder inflammation (Randich et al 2006), including earlyin-life bladder inflammation (DeBerry et al 2010), stress (Robbins and Ness 2008;Black et al 2009) and endogenous modulation (DeBerry et al 2007;Randich et al 2008) of responses to UBD have been reported, which further attest to the utility of this animal model.…”

Section: Urinary Bladder Distensionmentioning

confidence: 78%

Visceral Pain

Schwartz¹,

Gebhart²

2014

Current Topics in Behavioral Neurosciences

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Modeling visceral pain requires an appreciation of the underlying neurobiology of visceral sensation, including characteristics of visceral pain that distinguish it from pain arising from other tissues, the unique sensory innervation of visceral organs, the functional basis of visceral pain, and the concept of viscero-somatic and viscero-visceral convergence. Further, stimuli that are noxious when applied to the viscera are different than stimuli noxious to skin, muscle, and joints, thus informing model development and assessment. Visceral pain remains an important and understudied area of pain research and basic science knowledge and mechanisms acquired using animal models can translate into approaches that can be applied to the study and development of future therapeutics.

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“…Several preclinical studies have demonstrated that the exposure to bladder inflammation early-in-life can cause long-term alteration in sensory pain processing during adulthood [6; 17; 26]. We have recently demonstrated a long-term down-regulation of GABA Aα-1 receptor subunit expression in spinal neurons following neonatal cystitis and intrathecal administration of GABA A receptor agonist muscimol that failed to attenuate the visceromotor response in these hyperalgesic rats indicating an impairment of postsynaptic GABA transmission [35].…”

Section: Discussionmentioning

confidence: 99%

“…The intrinsic mechanism of early-life noxious stimuli-induced permanent alteration in nociceptive processing is not fully understood. It has been proposed that midbrain (RVM) descending inhibitory and facilitatory systems, which are involved in modulating pain behavior, are possibly affected, [26]. Impairment of the opioid inhibitory pathway has been implicated in the development of painful bladder disorders in animals that have experienced bladder inflammation early in life [6].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA–mediated downregulation of potassium-chloride-cotransporter and vesicular γ-aminobutyric acid transporter expression in spinal cord contributes to neonatal cystitis–induced visceral pain in rats

Zhang

Kannampalli

et al. 2017

Pain

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Loss of GABAergic inhibition in pain pathways has been considered to be a key component in the development of chronic pain. In the present study, we intended to examine whether miR-92b–mediated posttranscriptional dysregulation of spinal potassium chloride cotransporter (KCC2) and vesicular γ-aminobutyric acid transporter (VGAT) plays a major role in the development and maintenance of long-term visceral hyperalgesia in neonatal zymosan–treated rats. Neonatal cystitis was induced by transurethral zymosan administration from postnatal (P) days 14 to 16 (protocol 1). Two other zymosan protocols were also used: adult rechallenge on P57 to 59 following neonatal P14 to 16 exposures (protocol 2), and adult zymosan exposures on P57 to 59 (protocol 3). Both neonatal and adult bladder inflammation protocols demonstrated an increase in spinal miR-92b-3p expression and subsequent decrease in KCC2 and VGAT expression in spinal dorsal horn neurons. In situ hybridization demonstrated a significant upregulation of miR-92b-3p in the spinal dorsal horn neurons of neonatal cystitis rats compared with saline-treated controls. In dual in situ hybridization and immunohistochemistry studies, we further demonstrated coexpression of miR-92b-3p with targets KCC2 and VGAT in spinal dorsal horn neurons, emphasizing a possible regulatory role both at pre- and post-synaptic levels. Intrathecal administration of lentiviral pLSyn-miR-92b-3p sponge (miR-92b-3p inhibitor) upregulated KCC2 and VGAT expression in spinal dorsal horn neurons. In behavioral studies, intrathecal administration of lentiviral miR-92b-3p sponge attenuated an increase in visceromotor responses and referred viscerosomatic hypersensitivity following the induction of cystitis. These findings indicate that miR-92b-3p–mediated posttranscriptional regulation of spinal GABAergic system plays an important role in sensory pathophysiology of zymosan-induced cystitis.

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Rostral Ventral Medulla Modulation of the Visceromotor Reflex Evoked by Urinary Bladder Distension in Female Rats

Cited by 25 publications

References 27 publications

Urine Trouble: Alterations in Brain Function Associated with Bladder Pain

Urine Trouble: Alterations in Brain Function Associated with Bladder Pain

Visceral Pain

MicroRNA–mediated downregulation of potassium-chloride-cotransporter and vesicular γ-aminobutyric acid transporter expression in spinal cord contributes to neonatal cystitis–induced visceral pain in rats

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