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Dural administration of inflammatory soup or Complete Freund's Adjuvant induces activation and inflammatory response in the rat trigeminal ganglion.

Lukács M, Haanes KA, Majláth Z, Tajti J, Vécsei L, Warfvinge K, Edvinsson L - J Headache Pain (2015)

Bottom Line: We hypothesize that migraine pain originates from a central mechanism that results secondarily in hypersensitivity in peripheral afferents associated with the cerebral and cranial blood vessels.Myography resulted in a strong vasoconstrictor response to IS, but not to CFA.These results suggest that the application of IS or CFA onto the dura mater causes long-term activation of the TG and demonstrate the importance of the neuro-glial interaction in the activation of the trigeminovascular system.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Institute of Clinical Sciences, Division of Experimental Vascular Research, Lund University, Sölvegatan 17, SE 221 84, Lund, Sweden.

ABSTRACT

Background: Migraine is a painful disorder with a huge impact on individual and public health. We hypothesize that migraine pain originates from a central mechanism that results secondarily in hypersensitivity in peripheral afferents associated with the cerebral and cranial blood vessels. It has previously been shown that application of inflammatory or algesic substances onto the dura mater or chemical stimulation of the dural receptive fields causes hypersensitivity to mechanical and thermal stimulation together with direct activation of the TG. We asked whether local inflammation of dura mater induces inflammatory activation in the trigeminal ganglion.

Methods: We performed topical administration of inflammatory soup (IS) or Complete Freund's Adjuvant (CFA) onto an exposed area of the rat dura mater in vivo for 20 min. The window was closed and the rats were sacrificed after 4 h and up to 7 days. Myography was performed on middle meningeal arteries. The trigeminal ganglia were removed and processed for immunohistochemistry or Western blot.

Results: Both CFA and IS induced enhanced expression of pERK1/2, IL-1β and CGRP in the trigeminal ganglia. The pERK1/2 immunoreactivity was mainly seen in the satellite glial cells, while IL-1β reactivity was observed in the neuronal cytoplasm, close to the cell membrane, seemingly as sign of neuro-glial interaction. The CGRP expression in the neurons and nerve fibres was enhanced after the application of either inflammatory agent. Myography resulted in a strong vasoconstrictor response to IS, but not to CFA.

Conclusions: These results suggest that the application of IS or CFA onto the dura mater causes long-term activation of the TG and demonstrate the importance of the neuro-glial interaction in the activation of the trigeminovascular system.

No MeSH data available.


Related in: MedlinePlus

pERK immunohistochemistry on the TG. a. Negative control, showing no immunoreactivity. b. pERK1/2 staining in fresh animals. pERK positive nuclei (thin arrow) and nucleolei (thick arrow) can be detected. c. 24 h vehicle group shows weakly increased pERK1/2 immunoreactivity in the SGCs (thin arrow) and in the nucleolei (thick arrow). The TGs were studied at various time points (d-i). Positive immunoreactivity with different intensity can be detected in SGC (thin arrows) in all specimens. Negative SGC can also be seen (thick arrows). At 7 days CFA model, only few negative SGC were observed. Intensely stained nucleolei were also detected (arrow heads), more obvious at day 7 CFA. In the 7 days IS group, a lot of positive neuronal nuclei but no nucleolei were observed (asterisk)
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Fig2: pERK immunohistochemistry on the TG. a. Negative control, showing no immunoreactivity. b. pERK1/2 staining in fresh animals. pERK positive nuclei (thin arrow) and nucleolei (thick arrow) can be detected. c. 24 h vehicle group shows weakly increased pERK1/2 immunoreactivity in the SGCs (thin arrow) and in the nucleolei (thick arrow). The TGs were studied at various time points (d-i). Positive immunoreactivity with different intensity can be detected in SGC (thin arrows) in all specimens. Negative SGC can also be seen (thick arrows). At 7 days CFA model, only few negative SGC were observed. Intensely stained nucleolei were also detected (arrow heads), more obvious at day 7 CFA. In the 7 days IS group, a lot of positive neuronal nuclei but no nucleolei were observed (asterisk)

Mentions: pERK1/2 can be used as a dynamic, rapid and robust marker of noxious stimulation, as ERK1/2 phosphorylation can occur within a minute [21]. We were interested in the long term activation of pERK, as it could be related to permanent activation of the TG. pERK1/2 immunoreactivity was observed in a few nuclei and nucleoli of the neurons in the fresh TGs. No immunoreactivity was detected in the cytoplasm of the neurons or SGCs. In the 24 h vehicle group, some pERK1/2 immunoreactivity was found in the SGCs. The negative control, i.e. when the primary antibody was omitted, displayed no immunoreactivity (Fig. 2a-c).Fig. 2


Dural administration of inflammatory soup or Complete Freund's Adjuvant induces activation and inflammatory response in the rat trigeminal ganglion.

Lukács M, Haanes KA, Majláth Z, Tajti J, Vécsei L, Warfvinge K, Edvinsson L - J Headache Pain (2015)

pERK immunohistochemistry on the TG. a. Negative control, showing no immunoreactivity. b. pERK1/2 staining in fresh animals. pERK positive nuclei (thin arrow) and nucleolei (thick arrow) can be detected. c. 24 h vehicle group shows weakly increased pERK1/2 immunoreactivity in the SGCs (thin arrow) and in the nucleolei (thick arrow). The TGs were studied at various time points (d-i). Positive immunoreactivity with different intensity can be detected in SGC (thin arrows) in all specimens. Negative SGC can also be seen (thick arrows). At 7 days CFA model, only few negative SGC were observed. Intensely stained nucleolei were also detected (arrow heads), more obvious at day 7 CFA. In the 7 days IS group, a lot of positive neuronal nuclei but no nucleolei were observed (asterisk)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556720&req=5

Fig2: pERK immunohistochemistry on the TG. a. Negative control, showing no immunoreactivity. b. pERK1/2 staining in fresh animals. pERK positive nuclei (thin arrow) and nucleolei (thick arrow) can be detected. c. 24 h vehicle group shows weakly increased pERK1/2 immunoreactivity in the SGCs (thin arrow) and in the nucleolei (thick arrow). The TGs were studied at various time points (d-i). Positive immunoreactivity with different intensity can be detected in SGC (thin arrows) in all specimens. Negative SGC can also be seen (thick arrows). At 7 days CFA model, only few negative SGC were observed. Intensely stained nucleolei were also detected (arrow heads), more obvious at day 7 CFA. In the 7 days IS group, a lot of positive neuronal nuclei but no nucleolei were observed (asterisk)
Mentions: pERK1/2 can be used as a dynamic, rapid and robust marker of noxious stimulation, as ERK1/2 phosphorylation can occur within a minute [21]. We were interested in the long term activation of pERK, as it could be related to permanent activation of the TG. pERK1/2 immunoreactivity was observed in a few nuclei and nucleoli of the neurons in the fresh TGs. No immunoreactivity was detected in the cytoplasm of the neurons or SGCs. In the 24 h vehicle group, some pERK1/2 immunoreactivity was found in the SGCs. The negative control, i.e. when the primary antibody was omitted, displayed no immunoreactivity (Fig. 2a-c).Fig. 2

Bottom Line: We hypothesize that migraine pain originates from a central mechanism that results secondarily in hypersensitivity in peripheral afferents associated with the cerebral and cranial blood vessels.Myography resulted in a strong vasoconstrictor response to IS, but not to CFA.These results suggest that the application of IS or CFA onto the dura mater causes long-term activation of the TG and demonstrate the importance of the neuro-glial interaction in the activation of the trigeminovascular system.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Institute of Clinical Sciences, Division of Experimental Vascular Research, Lund University, Sölvegatan 17, SE 221 84, Lund, Sweden.

ABSTRACT

Background: Migraine is a painful disorder with a huge impact on individual and public health. We hypothesize that migraine pain originates from a central mechanism that results secondarily in hypersensitivity in peripheral afferents associated with the cerebral and cranial blood vessels. It has previously been shown that application of inflammatory or algesic substances onto the dura mater or chemical stimulation of the dural receptive fields causes hypersensitivity to mechanical and thermal stimulation together with direct activation of the TG. We asked whether local inflammation of dura mater induces inflammatory activation in the trigeminal ganglion.

Methods: We performed topical administration of inflammatory soup (IS) or Complete Freund's Adjuvant (CFA) onto an exposed area of the rat dura mater in vivo for 20 min. The window was closed and the rats were sacrificed after 4 h and up to 7 days. Myography was performed on middle meningeal arteries. The trigeminal ganglia were removed and processed for immunohistochemistry or Western blot.

Results: Both CFA and IS induced enhanced expression of pERK1/2, IL-1β and CGRP in the trigeminal ganglia. The pERK1/2 immunoreactivity was mainly seen in the satellite glial cells, while IL-1β reactivity was observed in the neuronal cytoplasm, close to the cell membrane, seemingly as sign of neuro-glial interaction. The CGRP expression in the neurons and nerve fibres was enhanced after the application of either inflammatory agent. Myography resulted in a strong vasoconstrictor response to IS, but not to CFA.

Conclusions: These results suggest that the application of IS or CFA onto the dura mater causes long-term activation of the TG and demonstrate the importance of the neuro-glial interaction in the activation of the trigeminovascular system.

No MeSH data available.


Related in: MedlinePlus