Ulcerative and Nonulcerative Forms of Bladder Pain Syndrome/Interstitial Cystitis Do Not Differ in Symptom Intensity or Response to Onabotulinum Toxin A

Pinto, Rui; Lopes, Teresa da Silva; Costa, Daniel L.; Barros, Sérgio; Silva, João; Silva, Carlos; Cruz, Carlos Oliveira; Dinis, Paulo; Cruz, Francisco

doi:10.1016/j.urology.2014.01.018

Cited by 54 publications

(40 citation statements)

References 17 publications

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“…Initial observations on the presence of growth factors in patients suffering from interstitial cystitis or bladder cancer demonstrated, among others, an increase of urinary GDNF [67]. More recently [68], urinary GDNF was shown to decrease in response to treatment of refractory bladder pain with the analgesic onabotulinum toxin A (OnabotA), although its basal levels in patients were not significantly different from those in normal subjects. The decrease in urinary GDNF after OnabotA indicated a local process of release, thus suggesting that GDNF could have a role in visceral pain in general, and in urinary bladder pain in particular.…”

Section: Human Studiesmentioning

confidence: 99%

Targeting the glial-derived neurotrophic factor and related molecules for controlling normal and pathologic pain

Merighi

2015

Expert Opinion on Therapeutic Targets

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Introduction: GDNF and its family of ligands (GFLs) have several functions in the nervous system. As a survival factor for dopaminergic neurons, GDNF was used in clinical trials for Parkinson's disease. However, GFLs their receptors are potential targets for new pain-controlling drugs. Such a potential should not be underestimated because molecules with analgesic activities in rodents mostly failed to be effective in translational studies. Areas covered:The circuitry, molecular and cellular mechanisms by which GFLs control nociception, their intervention in inflammatory and neuropathic pain, the problems related to effective GDNF delivery to the brain, the possibility to target the GFL receptor complex rather than its ligands, also by the use of non-peptidyl agonists, are discussed. Expert opinion:In nociceptive pathways, an ideal drug should either: i. Target the release of endogenous GFLs from large dense-cored vesicles (LGVs) by acting e.g. onto the phosphatidylinositol-3-phosphate [PtdIns(3)P] pool, which is sensitive to Ca 2+ modulation; ii. Target the GFL receptor complex. Besides to XIB403, a thiol molecule that enhances GFRα family receptor signaling, existing drugs such as retinoic acid and amitriptyline should be considered for effective targeting of GDNF, at least in neuropathic pain. The approach of pain modeling in experimental animals is discussed.

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Section: Human Studiesmentioning

confidence: 99%

Targeting the glial-derived neurotrophic factor and related molecules for controlling normal and pathologic pain

Merighi

2015

Expert Opinion on Therapeutic Targets

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“…144 Despite this finding, investigators in another study found that patients with ulcerative or nonulcerative IC/BPS had similar symp toms at baseline and comparable clinical responses to intratrigonal BoNTA injections. 145 This difference could be a result of the different definitions of ulcerative interstitial cystitis and different injection sites used in these studies.…”

Section: Ic/bpsmentioning

confidence: 97%

“…Some authors favoured tri gonal injection, 39,41,145 whereas others used bladder body injections, either including into the trigone, 138,140 or sparing the trigone. 139,[142][143][144] The therapeutic outcomes of these investigations were similar in patients with nonulcerativ e type IC/BPS but different in patients with ulcerative IC/BPS.…”

Section: Ic/bpsmentioning

confidence: 99%

“…139,[142][143][144] The therapeutic outcomes of these investigations were similar in patients with nonulcerativ e type IC/BPS but different in patients with ulcerative IC/BPS. 144,145 Despite the controversial results of smaller studies, findings of a randomized, doubleblind, placebo controlled, multicentre trial published in April 2015 showed that injections of 100 units of BoNTA effec tively reduced bladder pain symptoms in patients with IC/BPS. 146 At 8 weeks after treatment, a significantly greater reduction in pain scores was observed in the BoNTA group compared with the normal saline group (-2.6 ± 2.8 versus -0.9 ± 2.2; P = 0.02) and the frequency or severity of adverse events did not differ signifi cantly between the groups.…”

Section: Ic/bpsmentioning

confidence: 99%

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Current and potential urological applications of botulinum toxin A

Jiang

Liao

2015

Nat Rev Urol

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Botulinum toxin subtype A (BoNT-A) is a potent neurotoxin that can selectively modulate neurotransmitter release from nerve endings, resulting in muscular paralysis. BoNT-A might also act on sensory nerves, and have an anti-inflammatory effect. In the first urological use of BoNT-A, injection into the urethral sphincters of patients with detrusor-sphincter dyssynergia resulted in a reduction of urethral resistance and improved voiding efficiency. Subsequently, intravesical BoNT-A injections have received regulatory approval for treatment of neurogenic detrusor overactivity owing to spinal cord lesions or multiple sclerosis, and idiopathic overactive bladder in adults. BoNT-A has also been widely used to treat patients with the off-label indications of neurogenic or non-neurogenic voiding dysfunction and male lower urinary tract symptoms owing to BPH and bladder-neck dysfunction. Other indications for which urologists have applied BoNT-A injections include interstitial cystitis/bladder pain syndrome, bladder oversensitivity and chronic pelvic pain syndrome. BoNT-A is currently delivered as an intravesical injection; however, use of liposome encapsulated formulations is also beginning to show some therapeutic potential.

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“…Ein positiver E ekt konnte sowohl bei Patienten mit ulzeröser Manifestation der IC als auch bei Patienten ohne Ulzera der Harnblase festgestellt werden. Dies lässt darauf schließen, dass Ulzera nicht allein ursächlich für Blasenschmerzen sind [46]. Durch eine wiederholte intravesikale Applikation von Botolinumtoxin A konnten Blasenschmerzen gesenkt und das Blasenvolumen erhöht werden.…”

Section: Therapieunclassified