Botulinum Toxin as a Pain Killer: Players and Actions in Antinociception
Abstract
:1. Introduction
2. BoNTs Complex: Molecular Machines Invading Epithelia and Nerves
2.1. The Components of BoNTs Complex
2.2. The Role of NTNHA
2.3. HA and Gastrointestinal Absorption
2.4. Uptake at Nerve Endings
2.5. Translocation into the Cytosol to Be an Active Protease
3. BoNTs: A Pain Killer
3.1. Antinociceptive Actions of BoNTs
3.1.1. Glutamate, Substance P (SP) and Cacitonin-Gene Related Peptide (CGRP)
3.1.2. Transient Receptor Potential Vanilloids 1 (TRPV1)
3.1.3. GABAergic and Opioidergic Neurotransmission
3.1.4. Central Effects of BoNTs in Rat Models
3.1.5. Axonal Transport of BoNTs
BoNT/A injection | Pain model | Antinociceptive effects |
---|---|---|
Paws | Formalin induced inflammatory pain model [73,87,102] | Reduction of enhanced nocifensive behaviors (licking, flinching and shaking) [87,102] |
Reduction of c-fos early response gene expression [87,102] | ||
Reduction of enhanced glutamate release in primary afferent terminals [73] | ||
Sciatic nerve transection (CCI) induced neuropathic model [87,91,102,103,104] | Recovery of paw withdrawal response [87,91,102,103,104] | |
Cleaved cSNAP-25 detected in paw, sciatic nerve, DRG, and L4/L5 spinal cord (dorsal horn) [103] | ||
Recovery of thermal hyperalgesia [91,104] | ||
L5 ventral root transection (VRT) induced neuropathic model [93,94] | Bilateral recovery of decreased paw withdrawal thresholds [93,94] | |
Reduced expression of TRPV1 and P2X3 in dorsal root ganglion [93,94] | ||
Carrageenan-induced hyperalgesia [92,105] | Recovery of paw withdrawal response [92,105] | |
Recovery of thermal hyperalgesia [105] | ||
Reduction of c-fos early response gene expression in spinal cord [105] | ||
Paclitaxel-induced peripheral neuropathy model [92] | Bilateral recovery of decreased paw withdrawal thresholds [92] | |
Diabetic neuropathy pain model [106] | Bilateral recovery of decreased paw withdrawal thresholds [106] | |
Bilateral recovery of mechanical and thermal hypersensitivity [106] | ||
Acidic saline induced pain model [90] | Bilateral recovery of decreased paw withdrawal thresholds [90] | |
Spinal Cord | Sciatic nerve transection (SCI) induced neuropathic model [104] | Reduction of mechanical allodynia and thermal hyperalgesia [104] |
Diabetic neuropathy pain model [106] | Bilateral recovery of decreased paw withdrawal thresholds [106] | |
Bilateral recovery of mechanical and thermal hypersensitivity [106] | ||
Formalin induced inflammatory pain model [107] | Reduction of enhanced nocifensive behaviors (licking, flinching and shaking) [107] | |
Reduction of CGRP in spinal dorsal horn [107] | ||
Acetic acid induced abdominal pain [86] | Reduced writhes [86] | |
Reduction of increased c-fos expression in dorsal horn of the spinal cord (S2/S3segments) [86] | ||
Reduction of mechanical allodynia [86] | ||
Face | Formalin-induced facial pain (into the whisker pad) [108] | Reduction of facial rubbing [108] |
Cleaved cSNAP-25 detected in trigeminal nucleus caudalis (TNC) [108] | ||
Colchicine-sensitive [108] | ||
Infraorbital nerve constriction (IoNC) induced trigeminal neuropathy model [95] | Reduction of dural extravasation [95] | |
Colchicine-sensitive bilateral analgesic effect in trigeminal ganglion [95] |
3.2. Molecular Therapeutics of BoNTs
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Kim, D.-W.; Lee, S.-K.; Ahnn, J. Botulinum Toxin as a Pain Killer: Players and Actions in Antinociception. Toxins 2015, 7, 2435-2453. https://doi.org/10.3390/toxins7072435
Kim D-W, Lee S-K, Ahnn J. Botulinum Toxin as a Pain Killer: Players and Actions in Antinociception. Toxins. 2015; 7(7):2435-2453. https://doi.org/10.3390/toxins7072435
Chicago/Turabian StyleKim, Dong-Wan, Sun-Kyung Lee, and Joohong Ahnn. 2015. "Botulinum Toxin as a Pain Killer: Players and Actions in Antinociception" Toxins 7, no. 7: 2435-2453. https://doi.org/10.3390/toxins7072435