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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

IL-1β immunohistochemistry on the TG a. Negative control showing no immunoreactivity. b. IL-1β staining in fresh animals. Immunoreactive neuronal nuclei could be detected (thick arrow). In addition, an intracytoplasmatic granular staining was seen (thin arrow). c. 24 h vehicle group showed a similar pattern as for fresh animals. Inserts immunoreactive nerve fibers. d-i. Immunoreactivity was detected in the neuronal nuclei, but no nucleolei in the CFA and IS treated groups (thick arrows, d-i). In the cytoplasm immunoreactivity was detected in a granular manner (thin arrows, d-i). In the 7 days CFA and IS groups, increased immunoreactivity was seen as a condensed, homogeneous material close to the cell membrane (i, arrow heads)
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Fig4: IL-1β immunohistochemistry on the TG a. Negative control showing no immunoreactivity. b. IL-1β staining in fresh animals. Immunoreactive neuronal nuclei could be detected (thick arrow). In addition, an intracytoplasmatic granular staining was seen (thin arrow). c. 24 h vehicle group showed a similar pattern as for fresh animals. Inserts immunoreactive nerve fibers. d-i. Immunoreactivity was detected in the neuronal nuclei, but no nucleolei in the CFA and IS treated groups (thick arrows, d-i). In the cytoplasm immunoreactivity was detected in a granular manner (thin arrows, d-i). In the 7 days CFA and IS groups, increased immunoreactivity was seen as a condensed, homogeneous material close to the cell membrane (i, arrow heads)

Mentions: IL-1β plays a pivotal role in inflammation and has been shown to be present in the spinal cord, following the injection of CFA into the rat hind paw [22]. We were therefore interested if similar changes could occur in the TG after inflammatory activation. The negative control displayed no IL-1β immunoreactivity (Fig. 4a). In fresh TG, IL-1β immunoreactivity was observed in the neuronal cytoplasm (in a granular manner), in a few nuclei and in the nerve fibres (Fig. 4b). The same pattern was found in the vehicle-treated animals (Fig. 4c).Fig. 4


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)

IL-1β immunohistochemistry on the TG a. Negative control showing no immunoreactivity. b. IL-1β staining in fresh animals. Immunoreactive neuronal nuclei could be detected (thick arrow). In addition, an intracytoplasmatic granular staining was seen (thin arrow). c. 24 h vehicle group showed a similar pattern as for fresh animals. Inserts immunoreactive nerve fibers. d-i. Immunoreactivity was detected in the neuronal nuclei, but no nucleolei in the CFA and IS treated groups (thick arrows, d-i). In the cytoplasm immunoreactivity was detected in a granular manner (thin arrows, d-i). In the 7 days CFA and IS groups, increased immunoreactivity was seen as a condensed, homogeneous material close to the cell membrane (i, arrow heads)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig4: IL-1β immunohistochemistry on the TG a. Negative control showing no immunoreactivity. b. IL-1β staining in fresh animals. Immunoreactive neuronal nuclei could be detected (thick arrow). In addition, an intracytoplasmatic granular staining was seen (thin arrow). c. 24 h vehicle group showed a similar pattern as for fresh animals. Inserts immunoreactive nerve fibers. d-i. Immunoreactivity was detected in the neuronal nuclei, but no nucleolei in the CFA and IS treated groups (thick arrows, d-i). In the cytoplasm immunoreactivity was detected in a granular manner (thin arrows, d-i). In the 7 days CFA and IS groups, increased immunoreactivity was seen as a condensed, homogeneous material close to the cell membrane (i, arrow heads)
Mentions: IL-1β plays a pivotal role in inflammation and has been shown to be present in the spinal cord, following the injection of CFA into the rat hind paw [22]. We were therefore interested if similar changes could occur in the TG after inflammatory activation. The negative control displayed no IL-1β immunoreactivity (Fig. 4a). In fresh TG, IL-1β immunoreactivity was observed in the neuronal cytoplasm (in a granular manner), in a few nuclei and in the nerve fibres (Fig. 4b). The same pattern was found in the vehicle-treated animals (Fig. 4c).Fig. 4

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