The Analgesic Effect on Neuropathic Pain of Retrogradely Transported botulinum Neurotoxin A Involves Schwann Cells and Astrocytes

Sara Marinelli, Valentina Vacca, Ruggero Ricordy, Carolina Uggenti, Ada Maria Tata, Siro Luvisetto, Flaminia Pavone

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

In recent years a growing debate is about whether botulinum neurotoxins are retrogradely transported from the site of injection. Immunodetection of cleaved SNAP-25 (cl-SNAP-25), the protein of the SNARE complex targeted by botulinum neurotoxin serotype A (BoNT/A), could represent an excellent approach to investigate the mechanism of action on the nociceptive pathways at peripheral and/or central level. After peripheral administration of BoNT/A, we analyzed the expression of cl-SNAP-25, from the hindpaw's nerve endings to the spinal cord, together with the behavioral effects on neuropathic pain. We used the chronic constriction injury of the sciatic nerve in CD1 mice as animal model of neuropathic pain. We evaluated immunostaining of cl-SNAP-25 in the peripheral nerve endings, along the sciatic nerve, in dorsal root ganglia and in spinal dorsal horns after intraplantar injection of saline or BoNT/A, alone or colocalized with either glial fibrillar acidic protein, GFAP, or complement receptor 3/cluster of differentiation 11b, CD11b, or neuronal nuclei, NeuN, depending on the area investigated. Immunofluorescence analysis shows the presence of the cl-SNAP-25 in all tissues examined, from the peripheral endings to the spinal cord, suggesting a retrograde transport of BoNT/A. Moreover, we performed in vitro experiments to ascertain if BoNT/A was able to interact with the proliferative state of Schwann cells (SC). We found that BoNT/A modulates the proliferation of SC and inhibits the acetylcholine release from SC, evidencing a new biological effect of the toxin and further supporting the retrograde transport of the toxin along the nerve and its ability to influence regenerative processes. The present results strongly sustain a combinatorial action at peripheral and central neural levels and encourage the use of BoNT/A for the pathological pain conditions difficult to treat in clinical practice and dramatically impairing patients' quality of life.

Original languageEnglish
Article numbere47977
JournalPLoS One
Volume7
Issue number10
DOIs
Publication statusPublished - Oct 24 2012

Fingerprint

botulinum toxin
Schwann cells
Type A Botulinum Toxins
analgesic effect
astrocytes
Schwann Cells
Neurotoxins
Neuralgia
Astrocytes
Analgesics
pain
Cells
serotypes
nerve endings
nerve tissue
Nerve Endings
Sciatic Nerve
spinal cord
Spinal Cord
Biological Toxins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

The Analgesic Effect on Neuropathic Pain of Retrogradely Transported botulinum Neurotoxin A Involves Schwann Cells and Astrocytes. / Marinelli, Sara; Vacca, Valentina; Ricordy, Ruggero; Uggenti, Carolina; Tata, Ada Maria; Luvisetto, Siro; Pavone, Flaminia.

In: PLoS One, Vol. 7, No. 10, e47977, 24.10.2012.

Research output: Contribution to journalArticle

Marinelli, Sara ; Vacca, Valentina ; Ricordy, Ruggero ; Uggenti, Carolina ; Tata, Ada Maria ; Luvisetto, Siro ; Pavone, Flaminia. / The Analgesic Effect on Neuropathic Pain of Retrogradely Transported botulinum Neurotoxin A Involves Schwann Cells and Astrocytes. In: PLoS One. 2012 ; Vol. 7, No. 10.
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