Intrathecal administration of botulinum toxin type <scp>A</scp> improves urinary bladder function and reduces pain in rats with cystitis

Coelho, Ana; Oliveira, Raquel; Rossetto, Ornella; Cruz, Carlos Oliveira; Cruz, Francisco; Avelino, António

doi:10.1002/ejp.513

Cited by 36 publications

(28 citation statements)

References 35 publications

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“…In contrast to that, Coelho et al (2014) Considering that the only known target molecule for BTX-A is SNAP-25, we speculate that the inhibition of excitatory neurotransmitter release from the central endings of primary afferent terminals may be responsible for the antinociceptive action of BTX-A. Another possibility is that BTX-A, administered centrally, also inhibits neurotransmitter release from descending fibers, responsible for facilitation of pain transmission and generation of referred somatic and visceral hyperalgesia (Sanoja et al, 2010).…”

Section: Discussionmentioning

confidence: 79%

“…Another possibility is that BTX-A, administered centrally, also inhibits neurotransmitter release from descending fibers, responsible for facilitation of pain transmission and generation of referred somatic and visceral hyperalgesia (Sanoja et al, 2010). Coelho et al, 2014, …”

Section: Discussionmentioning

confidence: 99%

“…In addition, a few case reports pointed toward the beneficial effect of BTX-A in non-cardiac chest pain (Maradey-Romero and Fass, 2014) and perineal pain (Lim et al, 2010). Experimentally, the antinociceptive effect of BTX-A was investigated only in cystitis (Chuang et al, 2004, Coelho et al, 2014 and prostatitis (Chuang et al, 2008). In all listed reports and studies, the antinociceptive effect of primarily local BTX-A injections was examined.…”

Section: Introductionmentioning

confidence: 99%

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Antinociceptive effect of botulinum toxin type A on experimental abdominal pain

Drinovac

Bach-Rojecky

Babić

et al. 2014

European Journal of Pharmacology

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Antinociceptive effect of botulinum toxin type A on experimental abdominal pain

Drinovac

Bach-Rojecky

Babić

et al. 2014

European Journal of Pharmacology

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“…Preclinically, intrathecally administered BoNTs produced anti-hyperalgesic effects in various inflammatory and neuropathic hyperpathia. 297–300 The BoNT uptake is ubiquitous and the potent effects upon transmitter release may include inhibitory interneurons and motor neurons. 301,302 Several BoNT serotypes have been shown after topical application to be taken up and to block both local (peripheral) release from a nociceptor and to be transported centrally to inhibit downstream nociceptive processing, with indications of a possible pre- and post-synaptic effect.…”

Section: Survey Of Current Targets Of Pain Therapeuticsmentioning

confidence: 99%

Basic/Translational Development of Forthcoming Opioid- and Nonopioid-Targeted Pain Therapeutics

Knezevic

Yekkirala

Yaksh

2017

Anesthesia &Amp; Analgesia

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Opioids Opioids represent an efficacious therapeutic modality for some, but not all pain states. Singular reliance on opioid therapy for pain management, has limitations and abuse potential has deleterious consequences for patient and society. Our understanding of pain biology has yielded insights and opportunities for alternatives to conventional opioid agonists. The aim is to have efficacious therapies, with acceptable side effect profiles and minimal abuse potential, which is to say an absence of re-enforcing activity in the absence of a pain state. The present work provides a non-exclusive overview of current drug targets and potential future directions of research and development. We discuss channels activators and blockers, including: sodium channel blockers, potassium channel activators and calcium channel blockers; glutamate receptor targeted agents, including: NMDA, AMPA and metabotropic receptors). Further, we discuss therapeutics targeted at GABA, alpha2 adrenergic and opioid receptors. We also considered antagonists of angiotensin 2 and Toll receptors, and agonists/antagonists of adenosine, purine receptors. And cannabinoids. Novel targets considered are those focusing on lipid mediators and anti-inflammatory cytokines. Of interest is development of novel targeting strategies which produce long-term alterations in pain signaling, including viral transfection and toxins. We consider issues in the development of drugable molecules, including preclinical screening. While there are examples of successful translation, mechanistically promising pre-clinical candidates may unexpectedly fail during clinical trials because the preclinical models may not recapitulate the particular human pain condition being addressed. Molecular target characterization can diminish the disconnect between preclinical and humans’ targets, which should assist in developing non-addictive analgesics.

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“…By cleaving SNAREs, transmitter release is blocked and intracellular trafficking may be diminished. Intrathecal BoNTs have been shown to produce antihyperalgesic effects in a number of preclinical models of inflammatory and neuropathic hyperpathia [393][394][395][396]. The BoNT uptake is considered to be ubiquitous and the potent effects upon transmitter release may include inhibitory interneurons and motor neurons [397,398].…”

Section: Toxins Coupled To Agonists For G-protein-coupled Receptorsmentioning

confidence: 99%

Current and Future Issues in the development of spinal agents for the management of pain

Yaksh¹,

Fisher²,

Hockman³

et al. 2016

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Targeting analgesic drugs for spinal delivery reflects the fact that while the conscious experience of pain is mediated supraspinally, input initiated by high intensity stimuli, tissue injury and/or nerve injury is encoded at the level of the spinal dorsal horn and this output informs the brain as to the peripheral environment. This encoding process is subject to strong upregulation resulting in hyperesthetic states and downregulation reducing the ongoing processing of nociceptive stimuli reversing the hyperesthesia and pain processing. The present review addresses the biology of spinal nociceptive processing as relevant to the effects of intrathecally-delivered drugs in altering pain processing following acute stimulation, tissue inflammation/injury and nerve injury. The review covers i) the major classes of spinal agents currently employed as intrathecal analgesics (opioid agonists, alpha 2 agonists; sodium channel blockers; calcium channel blockers; NMDA blockers; GABA A/B agonists; COX inhibitors; ii) ongoing developments in the pharmacology of spinal therapeutics focusing on less studied agents/targets (cholinesterase inhibition; Adenosine agonists; iii) novel intrathecal targeting methodologies including gene-based approaches (viral vectors, plasmids, interfering RNAs); antisense, and toxins (botulinum toxins; resniferatoxin, substance P Saporin); and iv) issues relevant to intrathecal drug delivery (neuraxial drug distribution), infusate delivery profile, drug dosing, formulation and principals involved in the preclinical evaluation of intrathecal drug safety.Keywords: Adenovirus transfection, dorsal horn, neurotoxins, pain pathways, spinal drug delivery, spinal analgesics, toxicity. RATIONALETargeting analgesic drugs for direct spinal delivery reflects the fact that while the conscious experience of pain is mediated supraspinally, input initiated by high intensity stimuli, tissue injury and/or nerve injury is encoded at the level of the spinal dorsal horn. Thus, high intensity (e.g., nociceptive) stimulation activates populations of small primary afferents, generating an intensity-dependent increase in activity of second order dorsal horn projection neurons. This excitation is transmitted through spinofugal projection pathways to higher centers, such as the somatosensory thalamus -somatosensory cortex, and to the medial thalamus -limbic cortices that are respectively believed to underlie the sensory-discriminative and affectivemotivational components of the pain experience [1-3]. The dorsal horn encoding process reflects a remarkable plasticity wherein the input-output function of the spinal dorsal horn is subject to pronounced regulation by local neuronal and nonneuronal circuits as well as supraspinal (bulbospinal) input. Thus, following tissue or nerve injury there is an enhanced neuronal response to moderate or low intensity stimuli, e.g., *Address correspondence to this author at the University of California, San Diego, Anesthesia Research Lab 0818, 9500 Gilman Dr. LaJolla, CA 92093, USA; ...

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Intrathecal administration of botulinum toxin type A improves urinary bladder function and reduces pain in rats with cystitis

Abstract: Our findings suggest that i.t. Onabot/A has a strong analgesic effect in a model of severe bladder pain. This route of administration can be further explored to treat intractable forms of pain.

Cited by 36 publications

References 35 publications

Antinociceptive effect of botulinum toxin type A on experimental abdominal pain

Antinociceptive effect of botulinum toxin type A on experimental abdominal pain

Basic/Translational Development of Forthcoming Opioid- and Nonopioid-Targeted Pain Therapeutics

Current and Future Issues in the development of spinal agents for the management of pain

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