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

Abstract 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) upregula...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

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In this study, we sought to determine whether altered TLR4 activation plays a role in pelvic/bladder pain seen in IC/BPS patients using our validated IC/BPS-like transgenic autoimmune cystitis model (URO-OVA). URO-OVA mice developed responses consistent with pelvic and bladder pain after cystitis induction, which was associated with increased splenocyte production of TLR4-mediated proinflammatory cytokines interleukin (IL)-1b, IL-6 and tumor necrosis factor (TNF)-a. Increased spinal expression of mRNAs for proinflammatory cytokines IL-6 and TNF-a, glial activation markers CD11b and glial fibrillary acidic protein (GFAP), a...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research
This study also found that Proteus DNA, a genus with many uropathogenic species (Drzewiecka, 2016), was more prevalent in women with OAB compared to asymptomatic controls (Curtiss et al., 2017). IC A recent study by Abernethy et al. suggested that the microbiome may play a role in IC (Abernethy et al., 2017). In this study, 16S rRNA analysis determined the microbiome of catheterized urine from women (n = 40) with IC was not dominated by a single genus and was less likely to contain Lactobacillus compared to asymptomatic women. Abernethy et al. also showed that L. acidophilus was associated with less severe scores on the ...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
Kate V. Meriwether1*, Zhenmin Lei1, Rajbir Singh2, Jeremy Gaskins3, Deslyn T. G. Hobson1 and Venkatakrishna Jala2 1Department of Obstetrics and Gynecology, University of Louisville, Louisville, KY, United States 2Department of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, United States 3Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY, United States Interstitial cystitis/bladder pain syndrome (ICBPS) may be related to an altered genitourinary microbiome. Our aim was to compare the vaginal and urinary microbiomes b...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
ConclusionLike most neuropathic pain states, CPP is resilient, difficult to manage, and typically unresponsive to the traditional therapeutics and SCS. Our case series demonstrates no only that DRGS is potentially effective, long ‐term treatment modality for CPP, but that the L1/S2 lead placement is the configuration of choice despite distinct differences in etiologies of pain and location.
Source: Neuromodulation: Technology at the Neural Interface - Category: Biotechnology Authors: Tags: Case Series Source Type: research
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a prevalent, chronic bladder disorder that negatively impacts the quality of life for ∼5% of the western population. Hypersensitivity of mechanosensory afferents embedded within the bladder wall is considered a key component in mediating IC/BPS symptoms. Bladder infusion of voltage-gated sodium (Nav) channel blockers show clinical efficacy in treating IC/BPS symptoms; however, the current repertoire of Nav channels expressed by and contributing to bladder afferent function is unknown. We used single-cell reverse-transcription polymerase chain reaction of retrograd...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
Abstract Chronic abdominal and pelvic pain are common, debilitating clinical conditions experienced by millions of patients around the globe. The origin of such pain commonly arises from the intestine and bladder, which share common primary roles; the collection, storage and expulsion of waste. These visceral organs are located in close proximity to one another, and also share common innervation from spinal afferent pathways. Chronic abdominal pain, constipation or diarrhoea are primary symptoms for patients with Irritable Bowel Syndrome (IBS) or Inflammatory Bowel Disease (IBD). Chronic pelvic pain, urinary urgen...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research
Abstract Chronic pelvic pain causes significant patient morbidity and is a bane to clinicians. Using a murine neurogenic cystitis model that recapitulates key aspects of interstitial cystitis/bladder pain syndrome (IC), we recently showed that pseudorabies virus (PRV) induces severe pelvic allodynia in BALB/c mice, relative to C57BL/6 mice. Here, we report that a quantitative trait locus (QTL) analysis of PRV-induced allodynia in F2CxB progeny identified a polymorphism on chromosome 13, rs6314295, significantly associated with allodynia (LOD=3.11). The nearby gene encoding acyloxyacyl hydrolase, (Aoah), was induce...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - Category: Physiology Authors: Tags: Am J Physiol Regul Integr Comp Physiol Source Type: research
Approximately 100 million American adults experience chronic pain.35 Individuals' weight and gender place them at differential risk for chronic pain. Women report more pain than men20 and are more likely to develop pain conditions including fibromyalgia, migraine, or chronic tension-type headaches, irritable bowel syndrome, temporomandibular pain, and interstitial cystitis.2,20,43 In laboratory studies, women consistently show lower pain thresholds and tolerance than men.2 These findings are notable because of evidence from clinical settings that, compared with men, women are morelikely to have their pain undertreated, dis...
Source: The Journal of Pain - Category: Materials Science Authors: Tags: Original Report Source Type: research
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Source: Pain Practice - Category: Anesthesiology Authors: Tags: Case Report Source Type: research
Publication date: 27 March 2017 Source:Neuroscience, Volume 346 Author(s): Pradeep Kannampalli, Reji Babygirija, Jiang Zhang, Michael M. Poe, Guanguan Li, James M. Cook, Reza Shaker, Banani Banerjee, Jyoti N. Sengupta Painful events early in life have been shown to increase the incidence of interstitial cystitis/painful bladder syndrome in adulthood. However, the intrinsic mechanism is not well studied. We previously reported that neonatal bladder inflammation causes chronic visceral hypersensitivity along with molecular disruption of spinal GABAergic system in rats. The present study investigates whether these molecular ...
Source: Neuroscience - Category: Neuroscience Source Type: research
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