Botulinum Toxin in the Treatment of Headache

Becker, Werner J.

doi:10.3390/toxins12120803

Cited by 48 publications

(38 citation statements)

References 60 publications

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“…An alternative migraine treatment that has gained traction is the targeted blockade of CGRP exocytosis. In fact, botulinum neurotoxin type A (BoNT/A), a potent and specific inhibitor of transmitter release [25,26] due to truncation and inactivation of SNAP-25 (synaptosomal-associated protein with M r = 25k), received FDA approval (BOTOX ® , a complex of BoNT/A and non-toxic proteins) for treating chronic migraine but not the episodic form [27]. This came after BOTOX ® injections were shown in certain patients to reduce the frequency and severity of headache episodes in the Phase III Research Evaluating Migraine Prophylaxis (PREEMPT) series of clinical trials [28,29].…”

Section: Introductionmentioning

confidence: 99%

NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases

Belinskaia

Zurawski

Kaza

et al. 2022

IJMS

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Nerve growth factor (NGF) is known to intensify pain in various ways, so perturbing pertinent effects without negating its essential influences on neuronal functions could help the search for much-needed analgesics. Towards this goal, cultured neurons from neonatal rat trigeminal ganglia—a locus for craniofacial sensory nerves—were used to examine how NGF affects the Ca2+-dependent release of a pain mediator, calcitonin gene-related peptide (CGRP), that is triggered by activating a key signal transducer, transient receptor potential vanilloid 1 (TRPV1) with capsaicin (CAP). Measurements utilised neurons fed with or deprived of NGF for 2 days. Acute re-introduction of NGF induced Ca2+-dependent CGRP exocytosis that was inhibited by botulinum neurotoxin type A (BoNT/A) or a chimera of/E and/A (/EA), which truncated SNAP-25 (synaptosomal-associated protein with Mr = 25 k) at distinct sites. NGF additionally caused a Ca2+-independent enhancement of the neuropeptide release evoked by low concentrations (<100 nM) of CAP, but only marginally increased the peak response to ≥100 nM. Notably, BoNT/A inhibited CGRP exocytosis evoked by low but not high CAP concentrations, whereas/EA effectively reduced responses up to 1 µM CAP and inhibited to a greater extent its enhancement by NGF. In addition to establishing that sensitisation of sensory neurons to CAP by NGF is dependent on SNARE-mediated membrane fusion, insights were gleaned into the differential ability of two regions in the C-terminus of SNAP-25 (181–197 and 198–206) to support CAP-evoked Ca2+-dependent exocytosis at different intensities of stimulation.

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Section: Introductionmentioning

confidence: 99%

NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases

Belinskaia

Zurawski

Kaza

et al. 2022

IJMS

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“…Subsequent studies reported benefits from the use of onabotulinumtox-inA to treat migraine. In 2002, several headache experts indicated that onabotulinumtoxinA was safe and effective for prophylactic and acute treatment of migraine [13]. In 2010, the United States FDA approved Botox® for the treatment of chronic migraine.…”

Section: Onabotulinumtoxina and Headachesmentioning

confidence: 99%

“…Upon activation by stimuli, the sensory nerve endings of Cfibers in the meninges release neuropeptides. The role of on-abotulinumtoxinA in blocking the release of these neuropeptides from peripheral C-fiber nerve endings is most likely the key mechanism that underlies its therapeutic action against chronic migraine [13].…”

Section: Onabotulinumtoxina and Chronic Migrainementioning

confidence: 99%

OnabotulinumtoxinA for the treatment of headache: an updated review

Talbet¹,

Elnahry²

2022

J. Integr. Neurosci.

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Botulinum toxin (BT) is a neurotoxin produced by Clostridium botulinum, a gram-positive anaerobic bacterium. Systemic human intoxication from BT following oral ingestion results in acute and lifethreatening muscle paralysis called botulism. BT has a wide scope of therapeutic uses, including conditions associated with increased muscle tone, smooth muscle hyperactivity, salivation, sweating, and allergies, as well as for cosmetic purposes. Several commercial forms of BT are available for medical use, including Botox (onabotulinum-toxinA). Multiple studies have found evidence of an analgesic e fect of onabotulinumtoxinA and demonstrated the benefits of its use for the treatment of various chronic pain disorders. In this review, we provide an update on the use of onabotulinumtoxinA for the treatment of headache disorders.

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“…Intra-articular injection of BoNT/A complex can reduce joint pain severity with a significant improvement in function [14][15][16]. Moreover, BoNT/A complex (BOTOX) can also alleviate headache pain symptoms for a portion of migraine patients [16][17][18]. Currently, botulinum toxin injections have been US FDA approved for chronic migraines.…”

Section: Introductionmentioning

confidence: 99%

Selective Expression of a SNARE-Cleaving Protease in Peripheral Sensory Neurons Attenuates Pain-Related Gene Transcription and Neuropeptide Release

Wang

Kong

et al. 2021

IJMS

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Chronic pain is a leading health and socioeconomic problem and an unmet need exists for long-lasting analgesics. SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) are required for neuropeptide release and noxious signal transducer surface trafficking, thus, selective expression of the SNARE-cleaving light-chain protease of botulinum neurotoxin A (LCA) in peripheral sensory neurons could alleviate chronic pain. However, a safety concern to this approach is the lack of a sensory neuronal promoter to prevent the expression of LCA in the central nervous system. Towards this, we exploit the unique characteristics of Pirt (phosphoinositide-interacting regulator of TRP), which is expressed in peripheral nociceptive neurons. For the first time, we identified a Pirt promoter element and cloned it into a lentiviral vector driving transgene expression selectively in peripheral sensory neurons. Pirt promoter driven-LCA expression yielded rapid and concentration-dependent cleavage of SNAP-25 in cultured sensory neurons. Moreover, the transcripts of pain-related genes (TAC1, tachykinin precursor 1; CALCB, calcitonin gene-related peptide 2; HTR3A, 5-hydroxytryptamine receptor 3A; NPY2R, neuropeptide Y receptor Y2; GPR52, G protein-coupled receptor 52; SCN9A, sodium voltage-gated channel alpha subunit 9; TRPV1 and TRPA1, transient receptor potential cation channel subfamily V member 1 and subfamily A member 1) in pro-inflammatory cytokines stimulated sensory neurons were downregulated by viral mediated expression of LCA. Furthermore, viral expression of LCA yielded long-lasting inhibition of pain mediator release. Thus, we show that the engineered Pirt-LCA virus may provide a novel means for long lasting pain relief.

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Botulinum Toxin in the Treatment of Headache

Cited by 48 publications

References 60 publications

NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases

NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases

OnabotulinumtoxinA for the treatment of headache: an updated review

Selective Expression of a SNARE-Cleaving Protease in Peripheral Sensory Neurons Attenuates Pain-Related Gene Transcription and Neuropeptide Release

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