Selective cephalic upregulation of p-ERK, CamKII and p-CREB in response to glyceryl trinitrate infusion

Roshni Ramachandran; Sara Hougaard Pedersen; Dipak Vasantrao Amrutkar; Steffen Petersen; Julie Mie Jacobsen; Anders Hay-Schmidt; Jes Olesen; Inger Jansen-Olesen

doi:10.1177/0333102417722511

Selective cephalic upregulation of p-ERK, CamKII and p-CREB in response to glyceryl trinitrate infusion

Roshni Ramachandran, Sara Hougaard Pedersen, Dipak Vasantrao Amrutkar, Steffen Petersen, Julie Mie Jacobsen, Anders Hay-Schmidt, Jes Olesen, Inger Jansen-Olesen^*

^*Corresponding author for this work

1 Citation (Scopus)

Abstract

Background: A common characteristic of migraine-inducing substances is that they cause headache and no pain in other areas of the body. Few studies have compared pain mechanisms in the trigeminal and spinal systems and, so far, no major differences have been noted. We compared signalling molecules in the trigeminal and spinothalamic system after infusion of the migraine-provoking substance glyceryltrinitrate. Method: A catheter was placed in the femoral vein of rats and one week later glyceryltrinitrate 4 µg/kg/min was infused for 20 min. Protein expression in the dura mater, trigeminal ganglion, nucleus caudalis, dorsal root ganglion and the dorsal horn of the thoracic spinal cord was analysed at different time points using western blotting and immunohistochemistry. Results: Glyceryltrinitrate caused a threefold increase in expression of phosphorylated extracellular signal-regulated kinases at 30 min in the dura mater and nucleus caudalis (P < 0.05) and at 2 h in the trigeminal ganglion with very few expressions in the dorsal root ganglion. In the nucleus caudalis, expression of phosphorylated extracellular signal-regulated kinases and Cam KII increased 2.6-fold and 3.2-fold, respectively, at 2 h after glycerytrinitrate infusion (P < 0.01). p-CREB/ATF-1 upregulation was observed only at 30 min (P < 0.05) in the nucleus caudalis. None of these markers showed increased expression in the regions of thoracic spinal cord dorsal horn. Conclusion: The dura, trigeminal ganglion and nucleus caudalis are activated shortly after glycerytrinitrate infusion with long-lasting expression of phosphorylated extracellular signal-regulated kinases observed in the nucleus caudalis. These activations were not observed at the spinal level.

Original language	English
Journal	Cephalalgia
Volume	38
Issue number	6
Pages (from-to)	1057-1070
Number of pages	14
ISSN	0333-1024
DOIs	https://doi.org/10.1177/0333102417722511
Publication status	Published - 2018

Keywords

kinase
Migraine
nitroglycerin
trigeminal ganglion
trigeminal vascular system

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10.1177/0333102417722511

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@article{ad8439631b8449b58345908eb33570ba,

title = "Selective cephalic upregulation of p-ERK, CamKII and p-CREB in response to glyceryl trinitrate infusion",

abstract = "Background: A common characteristic of migraine-inducing substances is that they cause headache and no pain in other areas of the body. Few studies have compared pain mechanisms in the trigeminal and spinal systems and, so far, no major differences have been noted. We compared signalling molecules in the trigeminal and spinothalamic system after infusion of the migraine-provoking substance glyceryltrinitrate. Method: A catheter was placed in the femoral vein of rats and one week later glyceryltrinitrate 4 µg/kg/min was infused for 20 min. Protein expression in the dura mater, trigeminal ganglion, nucleus caudalis, dorsal root ganglion and the dorsal horn of the thoracic spinal cord was analysed at different time points using western blotting and immunohistochemistry. Results: Glyceryltrinitrate caused a threefold increase in expression of phosphorylated extracellular signal-regulated kinases at 30 min in the dura mater and nucleus caudalis (P < 0.05) and at 2 h in the trigeminal ganglion with very few expressions in the dorsal root ganglion. In the nucleus caudalis, expression of phosphorylated extracellular signal-regulated kinases and Cam KII increased 2.6-fold and 3.2-fold, respectively, at 2 h after glycerytrinitrate infusion (P < 0.01). p-CREB/ATF-1 upregulation was observed only at 30 min (P < 0.05) in the nucleus caudalis. None of these markers showed increased expression in the regions of thoracic spinal cord dorsal horn. Conclusion: The dura, trigeminal ganglion and nucleus caudalis are activated shortly after glycerytrinitrate infusion with long-lasting expression of phosphorylated extracellular signal-regulated kinases observed in the nucleus caudalis. These activations were not observed at the spinal level.",

keywords = "kinase, Migraine, nitroglycerin, trigeminal ganglion, trigeminal vascular system",

author = "Roshni Ramachandran and Pedersen, {Sara Hougaard} and Amrutkar, {Dipak Vasantrao} and Steffen Petersen and Jacobsen, {Julie Mie} and Anders Hay-Schmidt and Jes Olesen and Inger Jansen-Olesen",

year = "2018",

doi = "10.1177/0333102417722511",

language = "English",

volume = "38",

pages = "1057--1070",

journal = "Cephalalgia, Supplement",

issn = "0800-1952",

publisher = "SAGE Publications",

number = "6",

}

TY - JOUR

T1 - Selective cephalic upregulation of p-ERK, CamKII and p-CREB in response to glyceryl trinitrate infusion

AU - Ramachandran, Roshni

AU - Pedersen, Sara Hougaard

AU - Amrutkar, Dipak Vasantrao

AU - Petersen, Steffen

AU - Jacobsen, Julie Mie

AU - Hay-Schmidt, Anders

AU - Olesen, Jes

AU - Jansen-Olesen, Inger

PY - 2018

Y1 - 2018

N2 - Background: A common characteristic of migraine-inducing substances is that they cause headache and no pain in other areas of the body. Few studies have compared pain mechanisms in the trigeminal and spinal systems and, so far, no major differences have been noted. We compared signalling molecules in the trigeminal and spinothalamic system after infusion of the migraine-provoking substance glyceryltrinitrate. Method: A catheter was placed in the femoral vein of rats and one week later glyceryltrinitrate 4 µg/kg/min was infused for 20 min. Protein expression in the dura mater, trigeminal ganglion, nucleus caudalis, dorsal root ganglion and the dorsal horn of the thoracic spinal cord was analysed at different time points using western blotting and immunohistochemistry. Results: Glyceryltrinitrate caused a threefold increase in expression of phosphorylated extracellular signal-regulated kinases at 30 min in the dura mater and nucleus caudalis (P < 0.05) and at 2 h in the trigeminal ganglion with very few expressions in the dorsal root ganglion. In the nucleus caudalis, expression of phosphorylated extracellular signal-regulated kinases and Cam KII increased 2.6-fold and 3.2-fold, respectively, at 2 h after glycerytrinitrate infusion (P < 0.01). p-CREB/ATF-1 upregulation was observed only at 30 min (P < 0.05) in the nucleus caudalis. None of these markers showed increased expression in the regions of thoracic spinal cord dorsal horn. Conclusion: The dura, trigeminal ganglion and nucleus caudalis are activated shortly after glycerytrinitrate infusion with long-lasting expression of phosphorylated extracellular signal-regulated kinases observed in the nucleus caudalis. These activations were not observed at the spinal level.

AB - Background: A common characteristic of migraine-inducing substances is that they cause headache and no pain in other areas of the body. Few studies have compared pain mechanisms in the trigeminal and spinal systems and, so far, no major differences have been noted. We compared signalling molecules in the trigeminal and spinothalamic system after infusion of the migraine-provoking substance glyceryltrinitrate. Method: A catheter was placed in the femoral vein of rats and one week later glyceryltrinitrate 4 µg/kg/min was infused for 20 min. Protein expression in the dura mater, trigeminal ganglion, nucleus caudalis, dorsal root ganglion and the dorsal horn of the thoracic spinal cord was analysed at different time points using western blotting and immunohistochemistry. Results: Glyceryltrinitrate caused a threefold increase in expression of phosphorylated extracellular signal-regulated kinases at 30 min in the dura mater and nucleus caudalis (P < 0.05) and at 2 h in the trigeminal ganglion with very few expressions in the dorsal root ganglion. In the nucleus caudalis, expression of phosphorylated extracellular signal-regulated kinases and Cam KII increased 2.6-fold and 3.2-fold, respectively, at 2 h after glycerytrinitrate infusion (P < 0.01). p-CREB/ATF-1 upregulation was observed only at 30 min (P < 0.05) in the nucleus caudalis. None of these markers showed increased expression in the regions of thoracic spinal cord dorsal horn. Conclusion: The dura, trigeminal ganglion and nucleus caudalis are activated shortly after glycerytrinitrate infusion with long-lasting expression of phosphorylated extracellular signal-regulated kinases observed in the nucleus caudalis. These activations were not observed at the spinal level.

KW - kinase

KW - Migraine

KW - nitroglycerin

KW - trigeminal ganglion

KW - trigeminal vascular system

U2 - 10.1177/0333102417722511

DO - 10.1177/0333102417722511

M3 - Journal article

C2 - 28738691

AN - SCOPUS:85046808875

SN - 0800-1952

VL - 38

SP - 1057

EP - 1070

JO - Cephalalgia, Supplement

JF - Cephalalgia, Supplement

IS - 6

ER -

Selective cephalic upregulation of p-ERK, CamKII and p-CREB in response to glyceryl trinitrate infusion

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