The Effects of Intraplantar and Intrathecal Botulinum Toxin Type B on Tactile Allodynia in Mono and Polyneuropathy in the Mouse

Park, Hue Jung; Marino, Marc; Rondon, Eric Schmidt; Xu, Qing; Yaksh, Tony L.

doi:10.1213/ane.0000000000000777

Cited by 10 publications

(9 citation statements)

References 52 publications

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“…The threshold for tactile allodynia was measured with a series of von Frey filaments (von Frey Filaments; Bioseb, Vitrolles, France), ranging from 2.44 to 5.88 (0.03 -60.0 g), according to the methods of Park et al [28] and Zhu et al [29].…”

Section: Von Frey Testmentioning

confidence: 99%

Effect of Peptidase Inhibitors on Dynorphin A (1-17) or (1-13)-Induced Antinociception and Toxicity at Spinal Level

Matsuda¹,

Yoshikawa²,

Kan³

et al. 2017

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Our group has earlier demonstrated that three enzymes sensitive to peptidase inhibitors (PIs), amastatin (A)-, captopril (C)-, and phosphoramidon (P), played an important role in inactivation of enkephalins at the spinal level. Dynorphin-converting enzyme (DCE) hydrolyzes dynorphin (Dyn) A (1-17) or Dyn A (1-13) mainly at the Arg 6 -Arg 7 bond. Dynorphin A and its derived peptides interact with opioid and glutamate receptors at their N-and C-terminals, respectively. The purpose of the present study was to evaluate the antinociceptive potency and toxicity of intrathecal administered Dyn A (1-17), Dyn A (1-13), or Dyn A (1-6) under pretreatment with ACP and/or the DCE inhibitor p-hydroxymercuribenzoate (PHMB). The effect of these PIs on Dyn A (1-17)-induced inhibition of electrically-evoked contractions in mouse vas deferens was also investigated. The inhibitory potency of Dyn A (1-17) on electrically-evoked contractions in mouse vas deferens under pretreatment with ACP was higher than that with AC, AP, or CP. Pretreatment with ACP augmented Dyn A (1-17) or (1-13)-induced antinociception by approximately 50-or 30-fold with no sign of allodynia when administered intrathecally at low doses. Pretreatment with ACP and PHMB induced neuropathy. These findings showed that intrathecal administration of low-dose Dyn A (1-17) or DynA (1-13) increased antinociception under pretreatment with ACP, but without signs of allodynia in rat.

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Section: Von Frey Testmentioning

confidence: 99%

Effect of Peptidase Inhibitors on Dynorphin A (1-17) or (1-13)-Induced Antinociception and Toxicity at Spinal Level

Matsuda¹,

Yoshikawa²,

Kan³

et al. 2017

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“…It should be noted that in general the doses employed in these studies are typically in the range of 0.5–1 U, where 1 U is the dose that leads to mortality in half of the mice upon intraperitoneal injection. This reflects upon the fact that the intraplantar or subcutaneous injections result in a restricted redistribution as compared to that achieved with intraperitoneal delivery [ 67 , 84 , 99 ].…”

Section: Peripheral Delivery Of Botulinum Toxins and Nociception Imentioning

confidence: 99%

“…In rodent models, intraplantar delivery of BoNT/A1 and BoNT/B1 in doses of 0.5–1 U has been reported to reduce the allodynia observed in mononeuropathy models, including those of peripehral nerve ligation [ 84 , 85 ], ventral root transection [ 86 , 87 ], and infraorbital nerve constriction [ 74 ], and in polyneuropathy models, including those produced by chemotherpeutics [ 78 , 84 ] and diabetes [ 88 ]. As with the models of inflammation, these effects begin after ~1–2 days and last in excess of 21 days.…”

Section: Peripheral Delivery Of Botulinum Toxins and Nociception Imentioning

confidence: 99%

“…Consistent with these spinal actions outlined above, not surprisingly, intrathecal delivery of BoNT/B1 has been shown to result in cleavage of spinal SNAREs, blockade of evoked release of afferent transmitters and prevention of evoked activation of spinal neurons as indicated by the incidence of c-Fos (+) neurons [ 67 , 224 ]. Intrathecal delivery of BoNT/A1 and /B1 has been shown to block the second phase of IPLT formalin-evoked pain behavior [ 67 , 73 , 225 ] to reduce visceral-evoked inflammatory states (BoNT/A1) [ 226 ], and to attenuate the allodynia otherwise observed in mononeuropathies (nerve ligation) and polyneuropathies (as with chemotherapeutics) (BoNT/B1) [ 84 ]. The specificity of these effects on the role played by the cleavage of SNAREs was provided by two observations: i) intrathecal delivery of BoNT/B1 treated with dithiotreitol to cleave the disulfide linkages had no activity, and ii) intrathecal BoNT/B1 serotype blocked formalin-evoked flinching in the mouse but not in the rat, an observation consistent with the fact that the rat VAMP1 has a mutation at the BoNT/B1 targeted cleavage site rendering the rat insensitive to BoNT/B1 activity [ 227 ].…”

Section: Effects Of Peripherally Delivered Botulinum Toxins On Nocmentioning

confidence: 99%

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

Pellett

Yaksh

Ramachandran

2015

Toxins

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Current evidence suggests that botulinum neurotoxins (BoNTs) A1 and B1, given locally into peripheral tissues such as skin, muscles, and joints, alter nociceptive processing otherwise initiated by inflammation or nerve injury in animal models and humans. Recent data indicate that such locally delivered BoNTs exert not only local action on sensory afferent terminals but undergo transport to central afferent cell bodies (dorsal root ganglia) and spinal dorsal horn terminals, where they cleave SNAREs and block transmitter release. Increasing evidence supports the possibility of a trans-synaptic movement to alter postsynaptic function in neuronal and possibly non-neuronal (glial) cells. The vast majority of these studies have been conducted on BoNT/A1 and BoNT/B1, the only two pharmaceutically developed variants. However, now over 40 different subtypes of botulinum neurotoxins (BoNTs) have been identified. By combining our existing and rapidly growing understanding of BoNT/A1 and /B1 in altering nociceptive processing with explorations of the specific characteristics of the various toxins from this family, we may be able to discover or design novel, effective, and long-lasting pain therapeutics. This review will focus on our current understanding of the molecular mechanisms whereby BoNTs alter pain processing, and future directions in the development of these agents as pain therapeutics.

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“…Chemotherapieinduzierte schmerzhafte Neuropathien, durch Behandlung der Versuchstiere mit z. B. Paclitaxel oder Cisplatin, zeigten sich ebenfalls BoNTA responsiv (10,28). Auch bei diesem Modell ist der bilaterale analgetische BoNTA-Effekt nach unilateraler Applikation erwähnenswert.…”

Section: Neuropathische Schmerzmodelleunclassified

Botulinumtoxin zur Behandlung von neuropathischen Schmerzen

Sommer¹,

Üçeyler²

2017

Nervenheilkunde

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ZusammenfassungDie Behandlung neuropathischer Schmerzen mit systemisch wirksamen oral verabreichten Pharmaka ist bei vielen Patienten wirksam, kann jedoch zu zentralnervösen unerwünschten Wirkungen wie Müdigkeit oder Schwindel führen. Daher sind in den letzten Jahren topische Therapien in das Zentrum der Aufmerksamkeit gerückt. Botulinumtoxin, etabliert in der Therapie von Dystonien und Spastik, wurde zunehmend bei Schmerzerkrankungen getestet, hierbei ist Botulinum-Neurotoxin A der am besten untersuchte Serotyp. Die häufigsten Indikationen waren Schmerzen im Trigeminusversorgungsbereich und periphere neuropathische Schmerzen. Bei den meisten Studien war Botulinum-Neurotoxin A Placebo deutlich überlegen. Präklinische Studien zum Wirkmechanismus erbrachten die Erkenntnis, dass neben dem erwarteten peripheren Effekt sehr wahrscheinlich auch eine zentrale Reduktion der Ausschüttung von exzitatorischen Neurotransmittern an der Wirkung beteiligt ist.

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The Effects of Intraplantar and Intrathecal Botulinum Toxin Type B on Tactile Allodynia in Mono and Polyneuropathy in the Mouse

Abstract: BoNT-B given IPLT and IT yields a long-lasting attenuation of the allodynia in mice displaying MN and PN allodynia.

Cited by 10 publications

References 52 publications

Effect of Peptidase Inhibitors on Dynorphin A (1-17) or (1-13)-Induced Antinociception and Toxicity at Spinal Level

Effect of Peptidase Inhibitors on Dynorphin A (1-17) or (1-13)-Induced Antinociception and Toxicity at Spinal Level

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

Botulinumtoxin zur Behandlung von neuropathischen Schmerzen

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