Mapping of Pain Phenotypes in Female Patients with Bladder Pain Syndrome/Interstitial Cystitis and Controls

Tripp, Dean A.; Nickel, J. Curtis; Wong, Jennifer; Pontari, Michel A.; Moldwin, Robert; Mayer, Robert; Carr, Lesley K.; Doggweiler, Ragi; Yang, Claire C.; Mishra, Nagendra; Nordling, Jørgen

doi:10.1016/j.eururo.2012.05.023

Cited by 71 publications

(60 citation statements)

References 31 publications

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“…Little is known about the effects of CB2 activation on visceral pain. One hallmark of visceral pain is perception of pain arising from somatic sites distant from the area of visceral injury (referred hyperalgesia) (7)(8)42), and this is a relatively common finding in patients with IC/PBS (67). Sensitization of primary afferents at the site of injury plays an important role in development of referred hyperalgesia (8,78).…”

Section: Discussionmentioning

confidence: 99%

Activation of cannabinoid receptor 2 inhibits experimental cystitis

Wang

Bjorling

2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Cannabinoids have been shown to exert analgesic and anti-inflammatory effects, and the effects of cannabinoids are mediated primarily by cannabinoid receptors 1 and 2 (CB1and CB2). Both CB1 and CB2 are present in bladders of various species, including human, monkey, and rodents, and it appears that CB2 is highly expressed in urothelial cells. We investigated whether treatment with the CB2 agonist GP1a alters severity of experimental cystitis induced by acrolein and referred mechanical hyperalgesia associated with cystitis. We also investigated whether the mitogen-activated protein kinases (MAPK), ERK1/2, p38, and JNK are involved in the functions of CB2. We found that treatment with the selective CB2 agonist GP1a (1-10 mg/kg, ip) inhibited the severity of bladder inflammation 3 h after intravesical instillation of acrolein in a dose-dependent manner, and inhibition reached significance at a dose of 10 mg/kg (P < 0.05). Treatment with GP1a (10 mg/kg) inhibited referred mechanical hyperalgesia associated with cystitis (P < 0.05). The inhibitory effects of the CB2 agonist were prevented by the selective CB2 antagonist AM630 (10 mg/kg, sc). We further demonstrated the inhibitory effects of CB2 appear to be at least partly mediated by reducing bladder inflammation-induced activation of ERK1/2 MAPK pathway. The results of the current study indicate that CB2 is a potential therapeutic target for treatment of bladder inflammation and pain in patients.

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Section: Discussionmentioning

confidence: 99%

Activation of cannabinoid receptor 2 inhibits experimental cystitis

Wang

Bjorling

2013

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Therefore, effective management of IC/ BPS has not been established yet, and IC/BPS symptoms still result in a poor quality of life with sleep disruption, depression, and sexual dysfunction. [7][8][9] In addition, increased excitability of bladder afferent pathways has been proposed as a potential pathophysiological mechanism not only of hypersensitive bladder disorders such as IC/BPS, [10][11][12][13] but also of overactive bladder (OAB). 14 It has also been reported that the transient receptor potential vanilloid-1 (TRPV1) receptor, predominantly expressed in C-fiber afferent pathways, greatly contributes to afferent sensitization in chronic pain conditions.…”

Section: Introductionmentioning

confidence: 99%

Herpes Simplex Virus Vector-Mediated Gene Delivery of Poreless TRPV1 Channels Reduces Bladder Overactivity and Nociception in Rats

et al. 2015

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Increased afferent excitability has been proposed as an important pathophysiology of interstitial cystitis/ bladder pain syndrome (IC/BPS) and overactive bladder (OAB). In this study, we investigated whether herpes simplex virus (HSV) vectors encoding poreless TRPV1, in which the segment in C terminus of TRPV1 receptor is deleted, suppress bladder overactivity and pain behavior using a rat model of chemical cystitis. Replication-defective HSV vectors encoding poreless TRPV1 were injected into the bladder wall of adult female Sprague-Dawley rats. Additionally, recombinant HSV virus (vHG) vectors were injected as control. Cystometry (CMG) under urethane anesthesia was performed 1 week after viral injection to evaluate bladder overactivity induced by resiniferatoxin (RTx, a TRPV1 agonist). RTx-induced nociceptive behavior such as licking (lower abdominal licking) and freezing (motionless head-turning) was observed 2 weeks after viral injection. GFP expression in L4/L6/S1 dorsal root ganglia and the bladder as well as cFos-positive cells in the L6 spinal cord dorsal horn were also evaluated 2 weeks after viral injection. In CMG, the poreless TRPV1 vector-treated group showed a significantly smaller reduction in intercontraction intervals and voided volume after RTx infusion than the vHG-treated control group. The number of the RTx-induced freezing events was significantly decreased in the poreless TRPV1 group than in the vHG group, whereas there was no significant difference of the number of RTx-induced licking events between groups. The number of c-Fos-positive cells in the DCM and SPN regions of the L6 spinal dorsal horn was significantly smaller in the poreless TRPV1 group than in the vHG group. Our results indicated that HSV vector-mediated gene delivery of poreless TRPV1 had a therapeutic effect on TRPV1-mediated bladder overactivity and pain behavior. Thus, the HSV vector-mediated gene therapy targeting TRPV1 receptors could be a novel modality for the treatment of OAB and/or hypersensitive bladder disorders such as IC/BPS.

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“…Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic urological condition characterized by chronic pain in the pelvic, abdominal, and lower back areas, accompanied by urinary urgency and frequency, 1,2 with an unknown etiology and no standardized treatment. 3 Due to its refractory nature, treatment is focused on symptom and pain management, with psychosocial risk factors like depression as a subordinate concern.…”

Section: Introductionmentioning

confidence: 99%

Depression and catastrophizing predict suicidal ideation in tertiary care patients with interstitial cystitis/bladder pain syndrome

Tripp

Nickel

Krsmanovic

et al. 2016

CUAJ

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Introduction: We sought to evaluate psychosocial factors as predictors of suicidal ideation (SI) in a tertiary care outpatient sample of women suffering from interstitial cystitis/bladder pain syndrome (IC/BPS). Methods: The patients are women managed at tertiary care centres (n=190). Controls were recruited from the community (n=117). Both groups completed questionnaires on demographics, pain (McGill Pain Questionnaire), IC/BPS symptoms, and psychological variables. Univariate and multivariate hierarchical regression modelling was conducted to examine the strength of associations and unique effects of psychosocial variables on patient SI. Results: Compared to 6% in healthy controls, 23% of patients endorsed SI in the past two weeks. Correlations between SI, depression, and catastrophizing across controls and cases show that for controls, SI is associated with greater pain (0.31; p<0.01) and depression only (0.59; p<0.01). For tertiary care centre cases, SI is associated with pain (0.24; p<0.01), depression (0.64; p<0.01), and catastrophizing (0.35; p<0.01). Regression analyses indicated that psychosocial variables accounted for a significant amount of variance over and above IC/BPS symptoms. Catastrophizing (i.e., helplessness) about pain and depression were significant univariate predictors of SI, but only depression predicted SI in multivariable analyses. Conclusions: Limitations of this study include its cross-sectional design and primarily correlation-based statistics. The present study is the first to implicate multiple psychosocial risk factors over and above IC/BPS-specific symptoms and patient pain experience in SI in women with IC/BPS. Depression in particular is uniquely important in predicting suicidality. These results support a multidisciplinary, proactive approach to IC/BPS involving not only treatment of disease symptoms, but also early detection/treatment of associated psychosocial problems.

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Mapping of Pain Phenotypes in Female Patients with Bladder Pain Syndrome/Interstitial Cystitis and Controls

Cited by 71 publications

References 31 publications

Activation of cannabinoid receptor 2 inhibits experimental cystitis

Activation of cannabinoid receptor 2 inhibits experimental cystitis

Herpes Simplex Virus Vector-Mediated Gene Delivery of Poreless TRPV1 Channels Reduces Bladder Overactivity and Nociception in Rats

Depression and catastrophizing predict suicidal ideation in tertiary care patients with interstitial cystitis/bladder pain syndrome

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