Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/133128
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Type: Journal article
Title: Histamine induces peripheral and central hypersensitivity to bladder distension via the histamine H₁ receptor and TRPV1
Other Titles: Histamine induces peripheral and central hypersensitivity to bladder distension via the histamine H(1) receptor and TRPV1
Author: Grundy, L.
Caldwell, A.
Garcia Caraballo, S.
Erickson, A.
Schober, G.
Castro Kraftchenko, J.
Harrington, A.M.
Brierley, S.M.
Citation: American Journal of Physiology: Renal Physiology, 2020; 318(2):F298-F314
Publisher: American Physiological Society
Issue Date: 2020
ISSN: 1931-857X
1522-1466
Statement of
Responsibility: 
Luke Grundy, Ashlee Caldwell, Sonia Garcia Caraballo, Andelain Erickson, Gudrun Schober, Joel Castro ... et al.
Abstract: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a common chronic pelvic disorder with sensory symptoms of urinary urgency, frequency, and pain, indicating a key role for hypersensitivity of bladder-innervating sensory neurons. The inflammatory mast cell mediator histamine has long been implicated in IC/BPS, yet the direct interactions between histamine and bladder afferents remain unclear. In the present study, we show, using a mouse ex vivo bladder afferent preparation, that intravesical histamine enhanced the mechanosensitivity of subpopulations of afferents to bladder distension. Histamine also recruited "silent afferents" that were previously unresponsive to bladder distension. Furthermore, in vivo intravesical histamine enhanced activation of dorsal horn neurons within the lumbosacral spinal cord, indicating increased afferent signaling in the central nervous system. Quantitative RT-PCR revealed significant expression of histamine receptor subtypes (Hrh1-Hrh3) in mouse lumbosacral dorsal root ganglia (DRG), bladder detrusor smooth muscle, mucosa, and isolated urothelial cells. In DRG, Hrh1 was the most abundantly expressed. Acute histamine exposure evoked Ca2+ influx in select populations of DRG neurons but did not elicit calcium transients in isolated primary urothelial cells. Histamine-induced mechanical hypersensitivity ex vivo was abolished in the presence of the histamine H1 receptor antagonist pyrilamine and was not present in preparations from mice lacking transient receptor potential vanilloid 1 (TRPV1). Together, these results indicate that histamine enhances the sensitivity of bladder afferents to distension via interactions with histamine H1 receptor and TRPV1. This hypersensitivity translates to increased sensory input and activation in the spinal cord, which may underlie the symptoms of bladder hypersensitivity and pain experienced in IC/BPS.
Keywords: bladder
cystitis
histamine
hypersensitivity
neuron
transient receptor potential vanilloid 1
Rights: © 2020 the American Physiological Society
DOI: 10.1152/ajprenal.00435.2019
Appears in Collections:Medicine publications

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