Current Pharmacologic Approaches in Painful Bladder Research: An Update

Abstract

The symptoms of interstitial cystitis (IC)/bladder pain syndrome (BPS) may have multiple causes and involve many contributing factors. Traditional treatments (intravesical instillations) have had a primary focus on the bladder as origin of symptoms without adequately considering the potential influence of other local (pelvic) or systemic factors. Systemic pharmacological treatments have had modest success. A contributing factor to the low efficacy is the lack of phenotyping the patients. Individualized treatment based on is desirable, but further phenotype categorization is needed. There seems to be general agreement that IC is a unique disease and that BPS is a syndrome with multiple pathophysiologies, but this has so far not been not been well reflected in preclinical research with the aim of finding new pharmacological treatments. Current research approaches, including anti-nerve growth factor treatment, anti-tumor necrosis factor-α treatment, activation of SHIP1 (AQX-1125), and P2X3 receptor antagonists, and α1-adrenoceptor antagonists are potential systemic treatments, implying that not only the bladder is exposed to the administered drug, which may be beneficial if the IC/BPS is a bladder manifestation of a systemic disease, or negative (adverse effects) if it is a local bladder condition. Local treatment approaches such as the antagonism of Toll-like receptors (which still is only experimental) and intravesical liposomes (with positive proof-of-concept), may have the advantages of a low number of systemic adverse effects, but cannot be expected to have effects on symptoms generated outside the bladder. Assessment of which of the treatment approaches discussed in this review that can be developed into useful therapies requires further studies.

Expression and Function of Chemokines CXCL9-11 in Micturition Pathways in Cyclophosphamide (CYP)-Induced Cystitis and Somatic Sensitivity in Mice

“…Blockade of chemokine/receptor signaling may represent a potential therapeutic target for inflammation-associated bladder dysfunction (Tyagi et al, 2012 ; Gonzalez et al, 2014a ; Furuta et al, 2018 ). The heterogeneity of BPS/IC may underlie why few, effective treatments exist for the successful management of BPS/IC (Andersson and Birder, 2017 ). Thus, there is a clear need to identify novel targets for therapeutic intervention.…”

Modulatory effects of intravesical P2X2/3 purinergic receptor inhibition on lower urinary tract electromyographic properties and voiding function of female rats with moderate or severe spinal cord injury

“…Our present results suggest that SCI‐modified electrical nerve signals in the bladder and the EUS can lead to neurogenic LUT and that intravesical inhibition of P2X2/3R may be effective in managing voiding function at early stages following moderate but not severe SCI. Thus, the use of purinergic receptor antagonists should be considered, with some limitations, as an alternative pharmacotherapy for neurogenic LUT symptoms . Therefore, the efficacy of P2X3R antagonists for neurogenic and other LUT dysfunctions must be critically addressed using basic science tools before attempting any translational therapy seeking to improve function.…”

Response to Current Pharmacologic Approaches in Painful Bladder Research: An Update

“…I read, with great interest, the article “Current Pharmacologic Approaches in Painful Bladder Research: An Update” published by Karl-Erik Andersson and Lori Birder in Int Neurourol J on December 2017 [ 1 ], and would like to commend on the authors on their review article. The aim of this short review was to summarize the accumulating literature on interstitial cystitis/bladder pain syndrome (IC/BPS) and suggest ways that experimental findings could be applied to preclinical and clinical research.…”