scholarly journals Endogenous H2S sensitizes PAR4-induced bladder pain

2018 ◽  
Vol 314 (6) ◽  
pp. F1077-F1086 ◽  
Author(s):  
Wenfu Wang ◽  
Qiyu Bo ◽  
Jian Du ◽  
Xin Yu ◽  
Kejia Zhu ◽  
...  
Keyword(s):  
Pain Treatment ◽  
Intravesical Instillation ◽  
Aminooxyacetic Acid ◽  
Bladder Injury ◽  
Voiding Function ◽  
Bladder Pain ◽  
Protein Levels ◽  
Prominent Symptom ◽  
Pain Models ◽  
Painful Bladder

Bladder pain is a prominent symptom of interstitial cystitis/painful bladder syndrome. Hydrogen sulfide (H2S) generated by cystathionine β-synthase (CBS) or cystathionine γ-lyase (CSE) facilitates bladder hypersensitivity. We assessed involvement of the H2S pathway in protease-activated receptor 4 (PAR4)-induced bladder pain. A bladder pain model was induced by intravesical instillation of PAR4-activating peptide in mice. The role of H2S in this model was evaluated by intraperitoneal preadministration of d,l-propargylglycine (PAG), aminooxyacetic acid (AOAA), or S-adenosylmethionine or the preintravesical administration of NaHS. SV-HUC-1 cells were treated in similar manners. Assessments of CBS, CSE, and macrophage migration inhibitory factor (MIF) expression, bladder voiding function, bladder inflammation, H2S production, and referred bladder pain were performed. The CSE and CBS pathways existed in both mouse bladders and SV-HUC-1 cells. H2S signaling was upregulated in PAR4-induced bladder pain models, and H2S-generating enzyme activity was upregulated in human bladders, mouse bladders, and SV-HUC-1 cells. Pretreatment with AOAA or NaHS inhibited or promoted PAR4-induced mechanical hyperalgesia, respectively; however, PAG only partially inhibited PAR4-induced bladder pain. Treatment with PAG or AOAA decreased H2S production in both mouse bladders and SV-HUC-1 cells. Pretreatment with AOAA increased MIF protein levels in bladder tissues and cells, whereas pretreatment with NaHS lowered MIF protein levels. Bladder pain triggered by the H2S pathway was not accompanied by inflammation or altered micturition behavior. Thus endogenous H2S generated by CBS or CSE caused referred hyperalgesia mediated through MIF in mice with PAR4-induced bladder pain, without causing bladder injury or altering micturition behavior.

scholarly journals Hidrox ® and Chronic Cystitis: Biochemical Evaluation of Inflammation, Oxidative Stress, and Pain

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1046
Author(s):  
Ramona D’Amico ◽  
Angela Trovato Salinaro ◽  
Marika Cordaro ◽  
Roberta Fusco ◽  
Daniela Impellizzeri ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pain Treatment ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Bladder Pain ◽  
Symptom Intensity ◽  
Painful Bladder ◽  
The Central Nervous System ◽  
Inflammatory Infiltrates ◽  
Endothelial Junction

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic bladder condition characterized by frequent urination, inflammation, oxidative stress, and pain. The aim of the study was to evaluate the anti-inflammatory and antioxidant effects of an oral administration of Hidrox® (10 mg/kg) in the bladder and spinal cord in a rodent model of IC/BPS. The chronic animal model of cystitis was induced by repeated intraperitoneal injections of cyclophosphamide (CYP) for five consecutive days. Treatment with Hidrox ® began on the third day of the CYP injection and continued until the 10th day. CYP administration caused macroscopic and histological bladder changes, inflammatory infiltrates, increased mast cell numbers, oxidative stress, decreased expression of the tight endothelial junction (e.g., zonula occludens-1 (ZO-1) and occludin), and bladder pain. Treatment with Hidrox® was able to improve CYP-induced inflammation and oxidative stress via the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. It was also able to reduce bladder pain which was aggravated by the activation of neuroinflammation in the central nervous system. In particular, Hidrox® reduced the brain-derived neurotrophic factor (BDNF), as well as the activation of astrocytes and microglia, consequently reducing mechanical allodynia. These results indicate that nutritional consumption of Hidrox® can be considered as a new therapeutic approach for human cystitis, increasing the conceivable potential of a significant improvement in the quality of life associated with a lowering of symptom intensity in patients with IC/BPS.

289: Roles of Inducible Nitric Oxide Synthase in Voiding Function and Bladder Pain During Experimental Cystitis

2006 ◽  
Vol 175 (4S) ◽  
pp. 96-96
Author(s):  
Masayoshi Nomura ◽  
Hisae Nishii ◽  
Masato Tsutsui ◽  
Naohiro Fujimoto ◽  
Tetsuro Matsumoto
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Voiding Function ◽  
Bladder Pain ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

scholarly journals Protamine Sulfate Induced Bladder Injury Protects from Distention Induced Bladder Pain

2013 ◽  
Vol 189 (1) ◽  
pp. 343-351 ◽  
Author(s):  
Kristina M. Stemler ◽  
Lara W. Crock ◽  
H. Henry Lai ◽  
Jason C. Mills ◽  
Robert W. Gereau ◽  
...  
Keyword(s):  
Protamine Sulfate ◽  
Bladder Injury ◽  
Bladder Pain

scholarly journals Monoaminergic and Opioidergic Modulation of Brainstem Circuits: New Insights Into the Clinical Challenges of Pain Treatment?

2021 ◽  
Vol 2 ◽  
Author(s):  
Isaura Tavares ◽  
José Tiago Costa-Pereira ◽  
Isabel Martins
Keyword(s):  
Neuropathic Pain ◽  
Pain Control ◽  
Pain Treatment ◽  
Reticular Nucleus ◽  
Serotoninergic System ◽  
High Plasticity ◽  
Descending Facilitation ◽  
Pain Models ◽  
Dual Action ◽  
Control Circuits

The treatment of neuropathic pain remains a clinical challenge. Analgesic drugs and antidepressants are frequently ineffective, and opioids may induce side effects, including hyperalgesia. Recent results on brainstem pain modulatory circuits may explain those clinical challenges. The dual action of noradrenergic (NA) modulation was demonstrated in animal models of neuropathic pain. Besides the well-established antinociception due to spinal effects, the NA system may induce pronociception by directly acting on brainstem pain modulatory circuits, namely, at the locus coeruleus (LC) and medullary dorsal reticular nucleus (DRt). The serotoninergic system also has a dual action depending on the targeted spinal receptor, with an exacerbated activity of the excitatory 5-hydroxytryptamine 3 (5-HT3) receptors in neuropathic pain models. Opioids are involved in the modulation of descending modulatory circuits. During neuropathic pain, the opioidergic modulation of brainstem pain control areas is altered, with the release of enhanced local opioids along with reduced expression and desensitization of μ-opioid receptors (MOR). In the DRt, the installation of neuropathic pain increases the levels of enkephalins (ENKs) and induces desensitization of MOR, which may enhance descending facilitation (DF) from the DRt and impact the efficacy of exogenous opioids. On the whole, the data discussed in this review indicate the high plasticity of brainstem pain control circuits involving monoaminergic and opioidergic control. The data from studies of these neurochemical systems in neuropathic models indicate the importance of designing drugs that target multiple neurochemical systems, namely, maximizing the antinociceptive effects of antidepressants that inhibit the reuptake of serotonin and noradrenaline and preventing desensitization and tolerance of MOR at the brainstem.

Interstitial Cystitis/Bladder Pain Syndrome

2018 ◽  
Vol 36 (02) ◽  
pp. 123-135 ◽  
Author(s):  
Ioana Marcu ◽  
E. Campian ◽  
Frank Tu
Keyword(s):  
Interstitial Cystitis ◽  
Pelvic Pain ◽  
Pain Syndrome ◽  
Bladder Pain Syndrome ◽  
Bladder Pain ◽  
Painful Bladder ◽  
Bladder Symptoms ◽  
The Many ◽  
American Urological Association ◽  
Underlying Pathophysiology

AbstractInterstitial cystitis/bladder pain syndrome is an uncommon but potentially devastating pelvic pain disorder affecting both women and men. This condition is often confusable and comorbid with other pelvic pain disorders. Although our understanding of the underlying pathophysiology is growing, the exact longitudinal course by which peripheral and central aberrations involving the bladder mucosa, peripheral inflammation, and central dysregulation of bladder sensitivity create painful bladder symptoms remains an area in need of further study. Only a limited number of drugs have been approved for treatment by the Food and Drug Administration, and overall durable efficacy of the many treatments reviewed in recent American Urological Association guidelines remains suboptimal, making awareness, early diagnosis, and use of effective treatments early in the disease course, where neural changes may still be reversible, imperative.

scholarly journals Differential Regulation of Bladder Pain and Voiding Function by Sensory Afferent Populations Revealed by Selective Optogenetic Activation

2018 ◽  
Vol 12 ◽  
Author(s):  
Jennifer J. DeBerry ◽  
Vijay K. Samineni ◽  
Bryan A. Copits ◽  
Christopher J. Sullivan ◽  
Sherri K. Vogt ◽  
...  
Keyword(s):  
Differential Regulation ◽  
Voiding Function ◽  
Bladder Pain

scholarly journals Platelet-Rich Plasma Ameliorates Cyclophosphamide-Induced Acute Interstitial Cystitis/Painful Bladder Syndrome in a Rat Model

Diagnostics ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 381
Author(s):  
Yung-Hsiang Chen ◽  
Kee-Ming Man ◽  
Wen-Chi Chen ◽  
Po-Len Liu ◽  
Kao-Sung Tsai ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Interstitial Cystitis ◽  
Platelet Rich Plasma ◽  
Virgin Female ◽  
Intravesical Instillation ◽  
Painful Bladder Syndrome ◽  
Female Rats ◽  
Cell Junction ◽  
Control Group ◽  
Painful Bladder

Background: Interstitial cystitis/painful bladder syndrome (IC/PBS) could be treated to ameliorate urothelial injury. Here, we investigated the efficacy of intravesical instillation with platelet-rich plasma (PRP) and hyaluronic acid for acute IC/PBS. Methods: The effects of PRP and hyaluronic acid on the proliferation of normal human fibroblast cells (HFCs) were assessed. Additionally, thirty virgin female rats were randomized into five groups: group 1, saline-injected control; group 2, cyclophosphamide (CYP) plus intravesical instillation with normal saline; group 3, CYP plus intravesical instillation with hyaluronic acid (1 mg/mL); group 4, CYP plus intravesical instillation with PRP; and group 5, CYP plus intravesical instillation with PRP plus hyaluronic acid. A cystometry and histological assessments were performed. The expression of cell junction-associated protein zonula occludens-2 (ZO-2) and inflammatory cytokine interleukin 6 (IL-6) was also measured. Results: Low dose PRP increased proliferation in HFCs. The acute IC/PBS rats showed significantly lower voiding interval values. Voiding interval values were significantly higher in the CYP plus intravesical instillation with PRP group than in the CYP-induced acute IC/PBS group. Additionally, the expression of ZO-2 was increased and IL-6 was decreased in the CYP plus intravesical instillation with PRP group compared with the CYP-induced acute IC/PBS group. Conclusion: These findings suggest that PRP modulate urothelial repair, which ameliorate the increase in urination frequency in rats treated with CYP. Overall, PRP may confer potential benefits by acting as urothelial repair modulators.

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