Botulinum toxin in treating chronic pain.pptx

PPT for botulinum toxin

1. Botulinum toxin in treating chronic pain - what is the mechanism of action ?

2. Suggested reading Egeo G, Fofi L and Barbanti P (2020) Botulinum Neurotoxin for the Treatment of Neuropathic Pain. Front. Neurol. 11:716. doi : 10.3389/fneur.2020.00716 Ivica Matak et al. Mechanisms of Botulinum Toxin Type A Action on Pain. Toxins 2019, 11, 459; doi:10.3390/toxins11080459

3. Botulinum toxin ( 肉毒素 ) Derived from bacteria Clostridium botulinum. Seven serotypes of toxins Toxin A – G Human botulism: toxin A,B,E,F

4. Trade name 1. Onabotulinumtoxin A (Botox) 2. Abobotulinumtoxin A (Dysport) 3. Incobotulinumtoxin A ( Xeomin ) 4. Rimabotulinumtoxin B ( Myobloc )

5. Onabotulinuma toxin (Botox) FDA indications Ophthalmology Neurology Urology and gynecology

6. Non-dermatologic use of BoNT

7. Clinical studies – most RCTs showed improvement in VAS Egeo G, Fofi L and Barbanti P (2020) Botulinum Neurotoxin for the Treatment of Neuropathic Pain. Front. Neurol. 11:716. doi : 10.3389/fneur.2020.00716

8. RCTs in pain med. Most RCTs showed positive results Various in dose/indication

9. What is the mechanism of action?

10. Mechanism of action – inhibition of exocytosis Cleavage of SNARE proteins SNAP-25 Synapatobrevin VAMP Blocking the release of acetylcholine and other neurotransmitters Muscle paralysis Chemodenervation

11. Mechanism of action – inhibition of TRP channels * Sensory information is not equally affected by BoNTs BoNT /A mostly alleviates pathological inflammatory pain and mechanical sensation BoNTs reduce the expression of TRP channels in sensory neurons Go EJ et al. (2021) Transient Receptor Potential Channels and Botulinum Neurotoxins in Chronic Pain.  Front. Mol. Neurosci .  14:772719. March 2017 The Journal of Headache and Pain  18(1) DOI: 10.1186/s10194-017-0744-z

12. * TRPV1 TRPV1 的全名是 transient receptor potential vanilloid type 1 ，屬於 transient receptor potential (TRP) nonspecific cation channel family ( 短暫受體電位非特異性陽離子通道 ) 。它們 分布在各式各樣組織 的 感覺神經纖維末梢 (C-fiber) 上 ，例如眼睛，皮膚，血管，關節腔，肌肉與韌帶，及呼吸道、泌尿道、消化道等等。這些感覺細胞的本體則位於脊髓後根神經節或顱神經節中，統稱為多樣性傷害感受神經元 (polymodal nociceptor) 。 TRPV1 在偏頭痛發作扮演的角色 作者：台中童綜合醫院 王馨範 醫師 https://taiwanheadache.org.tw/wp-content/uploads/2021/06/epaper108.pdf

13. * TRPV1 ~cont. TRP 是一種多因受體。它接收許多性質迥異的、非特異性的激活因素以打開陽離子通道。這些激活因素目前已知包括有溫度 (>43°C) ，物理 / 機械性的傷害 (mechanical) ，酸 / 氫離子 (hydrogen ion) ，多種自然界物質如辣椒 (chili pepper) ，以及許多的具有刺激性的化學物質如丙烯醛，香菸等。 這些刺激或大或小，形成分散但可重複累積的陽離子流。 最終可以誘發該神經細胞向 efferent 端釋放出 Substance P(SP) ， Neurokinin(NK) ，與 CGRP 等神經胜肽 ，在組織間 ( 結膜、肺泡、腸道 ) 造成神經性發炎 ( neurogenic inflammation ) ，並同時 在 afferent 端則釋出 Glutamate 及 CGRP ，向中樞傳遞痛覺 。 TRPV1 在偏頭痛發作扮演的角色 作者：台中童綜合醫院 王馨範 醫師 https://taiwanheadache.org.tw/wp-content/uploads/2021/06/epaper108.pdf

14. Decrease peripheral and central sensitization Animal models Blocking the release of neurotransmitters and neuropeptides from nociceptive neurons Toxins   2010 ,  2 (12), 2890-2913;  https://doi.org/10.3390/toxins2122890

15. Mechanism of selectivity -SV receptors and endocytosis Membrane acceptor SV2 protein receptor Toxin uptake Endocytosis Selectivity of hyperactive nerve terminals Higher expression of SV2C expression

16. BoNT -A in treating pain in spinal cord injury “Retrograde axonal transport” theory : BTX applied to nerve ending not only affects afferent neurons  also acts on DRG and spinal dorsal horn. Immunohistochemical experiments have revealed that cleaved SNAP-25, a product of BTX-A action, is found not only in the peripheral region but also in the facial nucleus in the brain stem, superior colliculus, and motor region of the spinal cord.

17. Factors in BoNT -A

18. Factors in BoNT -A ~cont.

19. Sandrini et al. The Journal of Headache and Pain (2017) 18:38 inflammatory mediators (e.g., histamine, bradykinin, prostaglandins,

20. Thank you for your attention