Unmasking roles of the peripheral endocannabinoid system associated with bladder overactivity

Muñoz, Alvaro

doi:10.1111/bju.13336

Cited by 1 publication

(1 citation statement)

References 7 publications

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“…The transient receptor potential (TRP) channel TRPV1 is upregulated in the bladders of patients with OAB and IC/PBS (Liu and Kuo, 2007), whilst both TRPV1 and TRPA1 have consistently been implicated in mediating normal and cystitis-induced mechanical sensitivity in rodents by modulating neuronal activation thresholds and enhancing bladder afferent responses to P2X receptor activation (Daly et al, 2007; Wang et al, 2008; DeBerry et al, 2014, 2015b; Yoshiyama et al, 2015; Grundy et al, 2018b). A host of additional receptors and channels associated with nociception have also been identified upon bladder afferents that regulate neuronal sensitivity and neuronal excitability in animal models of cystitis, including voltage gated sodium (Na V ) channels (Erickson et al, 2018; Grundy et al, 2018d), potassium channels (K V ) (Hayashi et al, 2009), P2X receptors (Dang et al, 2008; Chen and Gebhart, 2010), TRPV4 (Merrill et al, 2012) and cannabinoid receptors (Hedlund, 2014; Izzo et al, 2015; Bakali et al, 2016; Hedlund and Gratzke, 2016; Munoz, 2016).…”

Section: Inflammationmentioning

confidence: 99%

Mechanisms Underlying Overactive Bladder and Interstitial Cystitis/Painful Bladder Syndrome

2018

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The bladder is innervated by extrinsic afferents that project into the dorsal horn of the spinal cord, providing sensory input to the micturition centers within the central nervous system. Under normal conditions, the continuous activation of these neurons during bladder distension goes mostly unnoticed. However, for patients with chronic urological disorders such as overactive bladder syndrome (OAB) and interstitial cystitis/painful bladder syndrome (IC/PBS), exaggerated bladder sensation and altered bladder function are common debilitating symptoms. Whilst considered to be separate pathological entities, there is now significant clinical and pre-clinical evidence that both OAB and IC/PBS are related to structural, synaptic, or intrinsic changes in the complex signaling pathways that mediate bladder sensation. This review discusses how urothelial dysfunction, bladder permeability, inflammation, and cross-organ sensitisation between visceral organs can regulate this neuroplasticity. Furthermore, we discuss how the emotional affective component of pain processing, involving dysregulation of the HPA axis and maladaptation to stress, anxiety and depression, can exacerbate aberrant bladder sensation and urological dysfunction. This review reveals the complex nature of urological disorders, highlighting numerous interconnected mechanisms in their pathogenesis. To find appropriate therapeutic treatments for these disorders, it is first essential to understand the mechanisms responsible, incorporating research from every level of the sensory pathway, from bladder to brain.

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