Current Status and Future Directions of Botulinum Neurotoxins for Targeting Pain Processing

Pellett, Sabine; Yaksh, Tony L.; Ramachandran, Roshni

doi:10.3390/toxins7114519

Cited by 71 publications

(58 citation statements)

References 315 publications

(420 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, botulinum neurotoxins A1 and B1 can alter nociceptive processing when administered locally into joints, and there is great interest in their potential application for OA pain (reviewed in [77]). Manipulation of the cannabinoid system is also heavily studied as an approach for OA pain management [78].…”

Section: Other Targetsmentioning

confidence: 99%

Emerging Targets for the Management of Osteoarthritis Pain

Malfait

Miller

2016

Curr Osteoporos Rep

View full text Add to dashboard Cite

Worldwide, osteoarthritis (OA) is one of the leading causes of chronic pain, for which adequate relief is not available. Ongoing peripheral input from the affected joint is a major factor in OA-associated pain. Therefore, this review focuses predominantly on peripheral targets emerging in the preclinical and clinical arena. Nerve growth factor is the most advanced of these targets, and its blockade has shown tremendous promise in clinical trials in knee OA. A number of different types of ion channels, including voltage-gated sodium channels and calcium channels, transient receptor potential channels and acid-sensing ion channels, are important for neuronal excitability and play a role in pain genesis. Few channel blockers have been tested in preclinical models of OA, with varying results. Finally, we discuss some examples of G-protein coupled receptors, which may offer attractive therapeutic strategies for OA pain, including receptors for bradykinin, calcitonin gene-related peptide, and chemokines. Since many of the pathways described above can be selectively and potently targeted, they offer an exciting opportunity for pain management in OA, either systemically or locally.

show abstract

Section: Other Targetsmentioning

confidence: 99%

Emerging Targets for the Management of Osteoarthritis Pain

Malfait

Miller

2016

Curr Osteoporos Rep

View full text Add to dashboard Cite

show abstract

“…Once inside, the complex is cleaved, freeing LC, which serves as enzyme cleaving SNARES. 294, 295 SNAREs mobilize vesicles for transmitter release and aid in the transport of GLUA1 AMPA receptor subunits to the membrane. 296 In case of SNARE cleavage, transmitter release is blocked.…”

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

View full text Add to dashboard Cite

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.

show abstract

“…Später kam auch die Applikation in fazialen Muskeln aus kosmetischen Gründen als Anwendungsgebiet hinzu. Weitere Indikationen sind die Hyperhidrose und neurogene Blasenstörungen [21,35,36,38,53]. Im Jahr 2010 folgte die FDA-Zulassung zur prophylaktischen Behandlung chronischer Migräne.…”

Section: Botulinumneurotoxinunclassified