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Modulation of inflammatory mediators in the trigeminal ganglion by botulinum neurotoxin type A: an organ culture study.

Edvinsson J, Warfvinge K, Edvinsson L - J Headache Pain (2015)

Bottom Line: Co-incubation with U0126 or BoNT-A retained the increased expression of SNAP-25, while it decreased the IL-1β immunoreactivity in neurons.It is clinically well recognized that treatment with corticosteroids will reduce the symptoms of chronic migraine; however this remedy is associated with long-term side effects.The results of the present work illustrate one way by which BoNT-A may modify these expressional alterations.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Lund University, Lund, Sweden, jacob.edvinsson@hotmail.com.

ABSTRACT

Background: Onabotulinumtoxin type A (BoNT-A) has been found to reduce pain in chronic migraine. The aim of the present study was to ask if BoNT-A can interact directly on sensory mechanisms in the trigeminal ganglion (TG) using an organ culture method.

Methods: To induce inflammation, rat TGs were incubated for 24 hrs with either the mitogen MEK1/2 inhibitor U0126, BoNT-A or NaCl. After this the TGs were prepared for immunohistochemistry. Sections of the TG were then incubated with primary antibodies against CGRP (neuronal transmitter), iNOS (inflammatory marker), IL-1β (Interleukin 1β), SNAP-25 (synaptic vesicle docking protein) or SV2-A (Botulinum toxin receptor element).

Results: We report that CGRP, iNOS, IL-1β, SNAP-25 and SV2-A were observed in fresh TG with a differential distribution. Interestingly, NaCl organ culture of the TG resulted in enhanced expression of CGRP and SNAP-25 in neurons and iNOS in SGCs. Co-incubation with U0126 or BoNT-A retained the increased expression of SNAP-25, while it decreased the IL-1β immunoreactivity in neurons. The iNOS expression in SGCs returned to levels observed in fresh specimens. Moreover, we observed no alteration SV2-A expression in SGCs. Thus, the overall picture is that both U0126 and BoNT-A have the ability to modify the expression of certain molecules in the TG.

Conclusion: We hypothesize that chronic migraine might be associated with some degree of inflammation in the TG that could involve both neurons and SGCs. It is clinically well recognized that treatment with corticosteroids will reduce the symptoms of chronic migraine; however this remedy is associated with long-term side effects. Understanding the mechanisms involved in the expressional alterations may suggest novel ways to modify the changes and indicate novel therapeutics. The results of the present work illustrate one way by which BoNT-A may modify these expressional alterations.

No MeSH data available.


Related in: MedlinePlus

Hematoxylin-Eosin staining. The column to the left shows the trigeminal ganglion in a fresh rat. The neurons were firmly enveloped by the SGC (arrows), demonstrating the close interaction between the neurons and glial cells. In comparison to a neuron, which contained a large pale nucleus and a visible nucleolus, the SGCs displayed a slender, slightly condensed nucleus. In the specimens that underwent incubation during 24 hrs, a similar morphology between the three groups was found: neurons with both condensed cytoplasm and nuclei, and enlarged rounded SGCs with highly condensed nuclei (arrows). In groups incubated with U0126 or BoNT-A, the neurons were often found in a vacuole indicating SGC detachment
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Fig1: Hematoxylin-Eosin staining. The column to the left shows the trigeminal ganglion in a fresh rat. The neurons were firmly enveloped by the SGC (arrows), demonstrating the close interaction between the neurons and glial cells. In comparison to a neuron, which contained a large pale nucleus and a visible nucleolus, the SGCs displayed a slender, slightly condensed nucleus. In the specimens that underwent incubation during 24 hrs, a similar morphology between the three groups was found: neurons with both condensed cytoplasm and nuclei, and enlarged rounded SGCs with highly condensed nuclei (arrows). In groups incubated with U0126 or BoNT-A, the neurons were often found in a vacuole indicating SGC detachment

Mentions: The morphology of the TG was evaluated following Htx staining (Fig. 1). Neurons of different size were firmly enveloped by SGCs, demonstrating the close interaction between the neurons and the glial cells. The neurons contained a large pale nucleus and a visible nucleolus, and the SGCs displayed a slender, slightly condensed nucleus.Fig. 1


Modulation of inflammatory mediators in the trigeminal ganglion by botulinum neurotoxin type A: an organ culture study.

Edvinsson J, Warfvinge K, Edvinsson L - J Headache Pain (2015)

Hematoxylin-Eosin staining. The column to the left shows the trigeminal ganglion in a fresh rat. The neurons were firmly enveloped by the SGC (arrows), demonstrating the close interaction between the neurons and glial cells. In comparison to a neuron, which contained a large pale nucleus and a visible nucleolus, the SGCs displayed a slender, slightly condensed nucleus. In the specimens that underwent incubation during 24 hrs, a similar morphology between the three groups was found: neurons with both condensed cytoplasm and nuclei, and enlarged rounded SGCs with highly condensed nuclei (arrows). In groups incubated with U0126 or BoNT-A, the neurons were often found in a vacuole indicating SGC detachment
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526514&req=5

Fig1: Hematoxylin-Eosin staining. The column to the left shows the trigeminal ganglion in a fresh rat. The neurons were firmly enveloped by the SGC (arrows), demonstrating the close interaction between the neurons and glial cells. In comparison to a neuron, which contained a large pale nucleus and a visible nucleolus, the SGCs displayed a slender, slightly condensed nucleus. In the specimens that underwent incubation during 24 hrs, a similar morphology between the three groups was found: neurons with both condensed cytoplasm and nuclei, and enlarged rounded SGCs with highly condensed nuclei (arrows). In groups incubated with U0126 or BoNT-A, the neurons were often found in a vacuole indicating SGC detachment
Mentions: The morphology of the TG was evaluated following Htx staining (Fig. 1). Neurons of different size were firmly enveloped by SGCs, demonstrating the close interaction between the neurons and the glial cells. The neurons contained a large pale nucleus and a visible nucleolus, and the SGCs displayed a slender, slightly condensed nucleus.Fig. 1

Bottom Line: Co-incubation with U0126 or BoNT-A retained the increased expression of SNAP-25, while it decreased the IL-1β immunoreactivity in neurons.It is clinically well recognized that treatment with corticosteroids will reduce the symptoms of chronic migraine; however this remedy is associated with long-term side effects.The results of the present work illustrate one way by which BoNT-A may modify these expressional alterations.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Lund University, Lund, Sweden, jacob.edvinsson@hotmail.com.

ABSTRACT

Background: Onabotulinumtoxin type A (BoNT-A) has been found to reduce pain in chronic migraine. The aim of the present study was to ask if BoNT-A can interact directly on sensory mechanisms in the trigeminal ganglion (TG) using an organ culture method.

Methods: To induce inflammation, rat TGs were incubated for 24 hrs with either the mitogen MEK1/2 inhibitor U0126, BoNT-A or NaCl. After this the TGs were prepared for immunohistochemistry. Sections of the TG were then incubated with primary antibodies against CGRP (neuronal transmitter), iNOS (inflammatory marker), IL-1β (Interleukin 1β), SNAP-25 (synaptic vesicle docking protein) or SV2-A (Botulinum toxin receptor element).

Results: We report that CGRP, iNOS, IL-1β, SNAP-25 and SV2-A were observed in fresh TG with a differential distribution. Interestingly, NaCl organ culture of the TG resulted in enhanced expression of CGRP and SNAP-25 in neurons and iNOS in SGCs. Co-incubation with U0126 or BoNT-A retained the increased expression of SNAP-25, while it decreased the IL-1β immunoreactivity in neurons. The iNOS expression in SGCs returned to levels observed in fresh specimens. Moreover, we observed no alteration SV2-A expression in SGCs. Thus, the overall picture is that both U0126 and BoNT-A have the ability to modify the expression of certain molecules in the TG.

Conclusion: We hypothesize that chronic migraine might be associated with some degree of inflammation in the TG that could involve both neurons and SGCs. It is clinically well recognized that treatment with corticosteroids will reduce the symptoms of chronic migraine; however this remedy is associated with long-term side effects. Understanding the mechanisms involved in the expressional alterations may suggest novel ways to modify the changes and indicate novel therapeutics. The results of the present work illustrate one way by which BoNT-A may modify these expressional alterations.

No MeSH data available.


Related in: MedlinePlus