TRP A1 Channels in Bladder Cells

Along with cytokines being a potential cause of the pain in IC my Urologist informed me that the new buzz is the effect of TRP A1 Channels in Bladder Cells on sensory neuropathy. That's a lot of big medical terms, again, bringing up my case about the layman being helpless to the doctors.

I found a nice site on Google that would lay it out for me, but after the first paragraph it said:

To read this article in full you may need to log in, make a payment or gain access through a site license (see right).

Injustice. This leads directly to why the poor has the worst health.. its not they just can't afford the medications, but they don't have either the education, the help, or the resources to research their options for themselves and are stuck playing Russian Roulette with doctors. The elderly fall into this pit too because of their "the doctor is always right mentality."

Thankfully my school has some articles up about it. Here's a few abstracts:

" • The pathophysiology of lower urinary tract symptoms (LUTS), detrusor overactivity (DO), and the overactive bladder (OAB) syndrome is multifactorial and remains poorly understood. • The transient receptor potential (TRP) channel superfamily has been shown to be involved in nociception and mechanosensory transduction in various organ systems, and studies of the LUT have indicated that several TRP channels, including TRPV1, TRPV2, TRPV4, TRPM8, and TRPA1, are expressed in the bladder, and may act as sensors of stretch and/or chemical irritation. • However, the roles of these individual channels for normal LUT function and in LUTS/DO/OAB, have not been established. • TRPV1 is the channel best investigated. It is widely distributed in LUT structures, but despite extensive information on morphology and function in animal models, the role of this channel in normal human bladder function is still controversial. Conversely, its role in the pathophysiology and treatment of particularly neurogenic DO is well established. • TRPV1 is co-expressed with TRPA1, and TRPA1 is known to be present on capsaicin-sensitive primary sensory neurones. Activation of this channel can induce DO in animal models. • TRPV4 is a Ca2+-permeable stretch-activated cation channel, involved in stretch-induced ATP release, and TRPV4-deficient mice exhibit abnormal frequencies of voiding and non-voiding contractions in cystometric experiments. • TRPM8 is a cool receptor expressed in the urothelium and suburothelial sensory fibres. It has been implicated in the bladder-cooling reflex and in idiopathic DO. • The occurrence of other members of the TRP superfamily in the LUT has been reported, but information on their effects on LUT functions is scarce. There seem to be several links between activation of different members of the TRP superfamily and LUTS/DO/OAB, and further exploration of the involvement of these channels in LUT function, normally and in dysfunction, may be rewarding. [ABSTRACT FROM AUTHOR]"

It sounds like its theory crafting for now, or at least, something difficult that will take time looking into. I could find nothing relating directly to IC and TRP A1 Channels, but I did find and article titled, "Autoimmunity to Uroplakin II Causes Cystitis in Mice: A Novel Model of Interstitial Cystitis."

The abstract is:

Abstract: Background: The pathophysiology of interstitial cystitis (IC) is unknown. Deficits in urothelial cell layers and autoimmune mechanisms may play a role. Objective: To examine whether immunization of mice with recombinant mouse uroplakin II (rmUPK2), a bladder-specific protein, would provoke an autoimmune response sufficient to create an IC phenotype. Design, setting, and participants: RmUPK2 complementary DNA was generated, transferred into a bacterial expression vector, and the generated protein was purified. Eight-week-old SWXJ female mice were immunized with rmUPK2 protein via subcutaneous injection of 200μg of rmUPK2 protein in 200μl of an emulsion. Measurements: Mice were euthanized 5 wk after immunization. Axillary and inguinal lymph node cells were tested for antigen-specific responsiveness and cytokine production, serum isotype antibody titers against rmUPK2 were determined, and gene expression of inflammatory mediators was measured in the bladder and other organs. For functional analysis, mice were placed in urodynamic chambers for 24-h micturition frequency and total voided urine measurements. Results and limitations: Immunization with rmUPK2 resulted in T-cell infiltration of the bladder urothelium and increased rmUPK2-specific serum antibody responses in the experimental autoimmune cystitis (EAC) mice models compared with controls. The ratio of bladder to body weight was increased in EAC mice. Quantitative reverse transcriptase polymerase chain reaction analysis showed elevated gene expression of tumor necrosis factor α, interferon γ, interleukin (IL)-17A, and IL-1β in bladder urothelium but not in other organs. Evaluation of 24-h micturition habits of EAC mice showed significantly increased urinary frequency (p 0.02) and significantly decreased urine output per void (p 0.021) when compared with control mice. Conclusions: Our study showed that a bladder-specific autoimmune response sufficient to induce inflammation and EAC occurs in mice following immunization with rmUPK2. EAC mice displayed significant evidence of urinary frequency and decreased urine output per void. Further phenotype characterization of EAC mice should include evidence for pain and/or afferent hypersensitivity, and evidence of urothelial cell layer damage. [Copyright &y& Elsevier]

But there's no full version of the study. It was released in January, but I like the looks of it. I always said my immune system was a freak of nature. I've been trying, TRYING to catch a cold or the flu for the past two years. Even when I was on the immune suppressant Cyclosporine I couldn't do it!

I guess keep our eyes peeled on the ICA and their reports.