Role of phosphorylated extracellular signal-regulated kinase, calcitonin gene-related peptide and cyclooxygenase-2 in experimental rat models of migraine

Abstract

Although migraine is a common neurological condition, the pathomechanism is not yet fully understood. Activation of the trigeminovascular system (TVS) has an important function in this disorder and neurogenic inflammation and central sensitization are important mechanisms underlying this condition. Nitroglycerin (NTG) infusion in rats closely mimics a universally accepted human model of migraine. Electrical stimulation of the trigeminal ganglion (ESTG) of rats can also activate TVS during a migraine attack. Numerous studies have revealed that phosphorylated extracellular signal-regulated kinase (p-ERK), calcitonin gene-related peptide (CGRP) and cyclooxygenase-2 (COX-2) are involved in pain and nociceptive pathways. However, few studies have examined whether p-ERK, CGRP and COX-2 are involved in neurogenic inflammation and central sensitization. In the present study, the expression of p-ERK, CGRP and COX-2 was detected in the dura mater, trigeminal ganglion (TG) and spinal trigeminal nucleus caudalis in NTG-induced rats and ESTG models by immunohistochemistry. The three areas considered were crucial components of the TVS. The selective COX-2 inhibitor nimesulide was used in ESTG rats to examine the association between p-ERK, CGRP and COX-2. The results demonstrated that p-ERK, CGRP and COX-2 mediated neurogenic inflammation and central sensitization in migraine. In addition, the expression of p-ERK and CGRP was attenuated by the COX-2 inhibitor.

Salmon calcitonin ameliorates migraine pain through modulation of CGRP release and dural mast cell degranulation in rats

“…Glyceryltrinitrate application is a very reliable representation and the most extensively accepted animal model of migraine that closely mimics the human glyceryl trinitrate headache model . The stimulation of the trigeminal ganglion in different animal models of migraine lead to the release of vasoactive and nociceptive neuropeptides such as CGRP and SP from trigeminal sensory nerve endings . The release of these neuropeptides following the activation of the trigeminal ganglion was shown to be responsible for the neurogenic inflammation.…”

“…The release of these neuropeptides following the activation of the trigeminal ganglion was shown to be responsible for the neurogenic inflammation. This is the phenomenon that underlies the pathophysiology of migraine . The increase in the plasma levels of CGRP is a biomarker for trigeminovascular activation during migraine attacks and cluster headaches .…”

“…17,18 The stimulation of the trigeminal ganglion in different animal models of migraine lead to the release of vasoactive and nociceptive neuropeptides such as CGRP and SP from trigeminal sensory nerve endings. 1 The release of these neuropeptides following the activation of the trigeminal ganglion was shown to be responsible for the neurogenic inflammation. This is the phenomenon that underlies the pathophysiology of migraine.…”

“…It is characterized by severe unilateral head pain, nausea, photophobia and phonophobia. It affects approximately 15% of the adult population worldwide . Although the exact pathophysiology of migraine remains unclear, it has been suggested that the activation of the trigeminovascular system (TVS), meninges and dural mast cells have pivotal roles in this condition .…”

“…It affects approximately 15% of the adult population worldwide. 1 Although the exact pathophysiology of migraine remains unclear, it has been suggested that the activation of the trigeminovascular system (TVS), meninges and dural mast cells have pivotal roles in this condition. 2-5 Calcitonin generelated peptide (CGRP) is a potent vasodilator neuropeptide and a key mediator in the pathophysiology of migraine.…”