Impairment of sensory afferents by intrathecal administration of botulinum toxin A improves neurogenic detrusor overactivity in chronic spinal cord injured rats

Coelho, Ana; Oliveira, Raquel; Cruz, Francisco; Cruz, Célia Duarte

doi:10.1016/j.expneurol.2016.05.029

Cited by 23 publications

(30 citation statements)

References 32 publications

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“…BoNT type A has also been shown to inhibit the release of CGRP from trigeminal ganglia and block its excitatory effects in the brain stem sensory neurons [28,29]. Intrathecal administration of BoNT significantly improved neurogenic detrussor overactivity in a chronic spinal cord injury model, as well as pain and bladder inflammation in a cystitis model in rats [30,31]. …”

Section: Discussionmentioning

confidence: 99%

Abobotulinum Toxin A in the Treatment of Chronic Low Back Pain

Machado

Kumar

Jabbari

2016

Toxins

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Chronic low back pain is a debilitating condition with a complex and multifactorial pathophysiology. Botulinum neurotoxins (BoNTs) have strong analgesic effects, as shown in both animal models of pain and in human beings. A randomized, double-blind, placebo-controlled, parallel format study to investigate the efficacy of abobotulinum toxin A (aboA) in chronic low back pain was conducted. The study cohort consisted of 18 patients who received 100 units of aboA into each of the five lumbar extensor spinae muscles unilaterally or bilaterally (total dose 500 to 1000 units), and 19 who received normal saline of the same volume. The level of pain and quality of life were assessed using the visual analogue scale (VAS) and three questionnaires including the Oswestry Low Back Pain Disability Questionnaire (OLBPDQ). Patients’ perception of improvement was recorded via patient global impression of change (PGIC). The primary outcome measure, the proportion of responders with VAS of <4 at 6 weeks, was not met, but the data was significantly in favor of aboA at 4 weeks (p = 0.008). The total Oswestry score representing quality of life improved in the aboA group compared to the placebo group (p = 0.0448). Moreover, significantly more patients reported their low back pain as “much improved” in the abobotulinum toxin A group (0.0293).

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Section: Discussionmentioning

confidence: 99%

Abobotulinum Toxin A in the Treatment of Chronic Low Back Pain

Machado

Kumar

Jabbari

2016

Toxins

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“…The proof of concept that BoNT/A has a strong activity on sensory terminals is that intrathecal administration of toxin has a predominant effect on sensory fibres and is enough to control neurogenic detrusor overactivity in chronic spinal cord injured rats (Coelho et al, 2016).…”

Section: Versatility Of Bont/a: the Bladder Paradigmmentioning

confidence: 99%

The binding of botulinum neurotoxins to different peripheral neurons

Rossetto

2018

Toxicon

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Botulinum neurotoxins are the most potent toxins known. The double receptor binding modality represents one of the most significant properties of botulinum neurotoxins and largely accounts for their incredible potency and lethality. Despite the high affinity and the very specific binding, botulinum neurotoxins are versatile and multi-tasking toxins. Indeed they are able to act both at the somatic and at the autonomic nervous system. In spite of the preference for cholinergic nerve terminals botulinum neurotoxins have been shown to inhibit to some extent also the noradrenergic postganglionic sympathetic nerve terminals and the afferent nerve terminals of the sensory neurons inhibiting the release of neuropeptides and glutamate, which are responsible of nociception. Therefore, there is increasing evidence that the therapeutic effect in both motor and autonomic disorders is based on a complex mode of botulinum neurotoxin action modulating the activity of efferent as well as afferent nerve fibres.

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“…Intravesical capsaicin and RTX are vanilloids that selectively block afferent nerves, which are rarely used clinically due to difficulty in delivery, inconsistent efficacy, and acute pain 6 . OnaBoNT-A injected into the bladder wall blocks both afferent and efferent nerves 7–9 , and recent studies suggest that restricting the action to only afferent nerves may improve the safety profile of onabotulinumtoxin 10 .…”

Section: Pathological and Therapeutic Denervation Of Bladdermentioning

confidence: 99%

Past, Present and Future of Chemodenervation with Botulinum Toxin in the Treatment of Overactive Bladder

et al. 2017

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Purpose We systematically reviewed both pre-clinical and clinical studies on bladder chemodenervation with onabotulinumtoxin A to highlight current limitations and future drug delivery approaches. Materials and Methods We identified peer-reviewed basic and clinical research studies of onabotulinumtoxin A (onaBoNT-A) in the treatment of neurogenic bladder and refractory idiopathic overactive bladder (OAB) published between March 2000 and March 2016. Paired investigators independently screened 125 English language articles to identify controlled studies on onaBoNT-A administration in MEDLINE® database and abstracts presented at annual American Urological Association meetings. The review yielded an evidence base of over 50 articles relevant to the approach of injection free onaBoNT-A chemodenervation. Results The efficacy and safety of intradetrusor injection of onaBoNT-A for the treatment of OAB is sensitive to both injection volume and depth, and this issue has motivated researchers to study injection-free modes of drug delivery into the bladder. Urothelial denudation with protamine sulfate or dimethyl sulfoxide (DMSO), liposome encapsulated onaBoNT-A, and other physical approaches are all being studied to increase toxin permeability and avoid intradetrusor injections. Liposome encapsulated onaBoNT-A enhances toxin activity while reducing its toxin degradation. The safety and efficacy of liposome encapsulated onaBoNT-A was tested in a multi-center, placebo controlled study. Although this treatment successfully reduced urinary frequency and urgency, it did not significantly reduce urgency urinary incontinence episodes. Conclusions Intradetrusor injection of onaBoNT-A is safe and effective as reported in several large multicenter randomized controlled trials. Injection of the toxin into the bladder wall impairs both afferent and efferent nerves, but drug delivery approaches that avoid injections impair only bladder afferent nerves. Further studies are needed to develop better drug delivery platforms that overcome the drawbacks of intradetrusor injection, increase patient acceptance, and reduce the treatment costs.

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Impairment of sensory afferents by intrathecal administration of botulinum toxin A improves neurogenic detrusor overactivity in chronic spinal cord injured rats

Cited by 23 publications

References 32 publications

Abobotulinum Toxin A in the Treatment of Chronic Low Back Pain

Abobotulinum Toxin A in the Treatment of Chronic Low Back Pain

The binding of botulinum neurotoxins to different peripheral neurons

Past, Present and Future of Chemodenervation with Botulinum Toxin in the Treatment of Overactive Bladder

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