Role of central versus peripheral opioid system in antinociceptive and anti‐inflammatory effect of botulinum toxin type A in trigeminal region

Vlah, V. Drinovac; Filipović, Boris; Bach-Rojecky, Lidija; Lacković, Zdravko

doi:10.1002/ejp.1146

Cited by 31 publications

(9 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, when BoNT-A was injected into the noninjured side, it prevented the pain only on that side. Those experiments clearly excluded passive spread of the toxin from the ipsilateral to the contralateral side (Bach-Rojecky and Lacković 2009; Drinovac Vlah et al 2017; Fig. 1).…”

Section: Changing Views On the Bont Mechanism Of Actionmentioning

confidence: 99%

“…Because enzymatic cleavage of SNAP-25 is the major molecular effect of BoNT-A, silencing of the central synapse of pseudounipolar sensory neurons seems the most logical mechanism of its central antinociceptive action. However, the picture might be more complex (Drinovac Vlah et al 2017). The role of axonal transport within motoneurons and possible transcytosis in the central nervous system is not yet clear (Fig.…”

Section: Changing Views On the Bont Mechanism Of Actionmentioning

confidence: 99%

See 1 more Smart Citation

Botulinum Toxin Type A in Dental Medicine

et al. 2019

Self Cite

View full text Add to dashboard Cite

Botulinum toxins (BoNTs) are a product of the bacteria Clostridium botulinum. By entering nerve endings, they cleave and inactivate SNARE proteins, which are essential for neurotransmitter release. Prevention of acetylcholine release at the neuromuscular junction causes long-lasting and potentially fatal flaccid paralysis—a major feature of botulism. However, an intramuscular injection of minute amounts of BoNTs, primarily type A (BoNT-A), has useful long-lasting muscle relaxation effects on spastic motor disorders. This characteristic of BoNT-A is widely used in neurology and cosmetics. Over the last few decades, it has been demonstrated that the functions of BoNT-A are not limited to muscle-relaxing or autonomic cholinergic effects but that it can act as an analgesic agent as well. More recently, it was revealed that this antinociceptive effect starts after entering the sensory nerve endings, where these agents are axonally transported to the central nervous system, suggesting that at least part of their analgesic effect might be of central origin. Because of its antinociceptive effect, BoNT-A is currently approved for treatment of chronic migraine; nonetheless, case reports and preclinical and clinical experiments indicating its benefit in numerous potential painful conditions have increased. In the field of dentistry, the US Food and Drug Administration approved BoNT-A for the treatment of sialorrhea only. Legal status of the use of BoNT-A in other countries is less known. However, there are controlled clinical trials suggesting its efficacy in other conditions, such as bruxism, temporomandibular disorders, and trigeminal neuropathic pain. Thereby, using criteria of the American Academy of Neurology, we critically reviewed the uses of BoNTs in oral medicine and found it effective for trigeminal neuralgia (category A) and probably effective in temporomandibular disorders and bruxism.

show abstract

Section: Changing Views On the Bont Mechanism Of Actionmentioning

confidence: 99%

Section: Changing Views On the Bont Mechanism Of Actionmentioning

confidence: 99%

Botulinum Toxin Type A in Dental Medicine

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although the opioid receptor antagonist naltrexone, as well as the GABA-A antagonist bicuculline, reduced BoNT/A effect on pain when applied intraperitoneally or intrathecally, the antagonistic effect was completely absent after their intracisternal and intracerebroventricular injection, thus providing evidence for segmental intraspinal action of BoNT/A on pain [24]. Furthermore, the analgesic action in the trigeminal innervation region also involves interactions with the central, not peripheral, endogenous opioid system, most likely at the level of trigeminal nucleus caudalis [108]. Interestingly, in the CCI-induced neuropathic pain model of mice, BoNT/A co-administration increased the morphine-induced analgesic response and reduced the tolerance to repeated morphine application accompanied with enhanced neuronal µ-opioid receptor expression [88,109].…”

Section: Actions Of Bont/a In the Central Nervous Systemmentioning

confidence: 99%

Mechanisms of Botulinum Toxin Type A Action on Pain

Matak

Bölcskei

Bach-Rojecky

et al. 2019

Toxins

165

127

View full text Add to dashboard Cite

Already a well-established treatment for different autonomic and movement disorders, the use of botulinum toxin type A (BoNT/A) in pain conditions is now continuously expanding. Currently, the only approved use of BoNT/A in relation to pain is the treatment of chronic migraines. However, controlled clinical studies show promising results in neuropathic and other chronic pain disorders. In comparison with other conventional and non-conventional analgesic drugs, the greatest advantages of BoNT/A use are its sustained effect after a single application and its safety. Its efficacy in certain therapy-resistant pain conditions is of special importance. Novel results in recent years has led to a better understanding of its actions, although further experimental and clinical research is warranted. Here, we summarize the effects contributing to these advantageous properties of BoNT/A in pain therapy, specific actions along the nociceptive pathway, consequences of its central activities, the molecular mechanisms of actions in neurons, and general pharmacokinetic parameters.

show abstract

“…Centrally, BTA also effects TRPV‐1 expression in central systems [144]. Finally, BTA might have an indirect action on endogenous opioids [148] and GABA [149] by enhancing their neurotransmission in the trigeminal innervation region [150]. Thus, the mechanism of action of BTA still warrants further investigation, but all these effects may be at work at different levels.…”

Section: State Of Ongoing Clinical Trialsmentioning

confidence: 99%

Cluster headache: state of the art of pharmacological treatments and therapeutic perspectives

Courault

Demarquay

Zimmer

et al. 2020

Fundamemntal Clinical Pharma

View full text Add to dashboard Cite

Cluster headache (CH) is the most common form of trigeminal autonomic cephalalgia. Current treatments have several limitations, and new drugs are required. This article first briefly reviews present acute and preventive treatments in CH, their mechanism of action and limitations, then describes the state of the art in recent clinical drug trials since 2015, and ends with a critique of trials in the CH field. Research is limited by lack of knowledge of pathophysiology and lack of animal models. In the past 5 years, no brand-new treatment has emerged, but promising drugs, such as CGRP(R) antibodies, are under study. According to the literature and guidelines, clinicians and researchers should be aware of many limitations in study protocols: concomitant medication, patient sample size, patients' protocol compliance, and study designs that tend to restrict patient recruitment.

show abstract

Role of central versus peripheral opioid system in antinociceptive and anti‐inflammatory effect of botulinum toxin type A in trigeminal region

Cited by 31 publications

References 42 publications

Botulinum Toxin Type A in Dental Medicine

Botulinum Toxin Type A in Dental Medicine

Mechanisms of Botulinum Toxin Type A Action on Pain

Cluster headache: state of the art of pharmacological treatments and therapeutic perspectives

Contact Info

Product

Resources

About