Zeinab Ghorbani PhD Candidate in Nutritional Sciences School of Nutritional Sciences and Dietetics Tehran University of Medical Sciences TUMS Introduction Top 10 level4 causes of disability in GBD 2016 global both sexes all ages ID: 915335
Download Presentation The PPT/PDF document "Neurogenic Inflammation and Migraine" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Neurogenic Inflammation and Migraine
Zeinab GhorbaniPh.D Candidate in Nutritional Sciences, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS).
Slide2Introduction
Top 10 level-4 causes of disability in GBD 2016 (global, both sexes, all ages)
Low back painMigraine
Age-related hearing loss
Iron-deficiency anaemia
Major depression
Neck pain
Other musculoskeletal disorders
Diabetes
Anxiety disorders
Falls
Migraine
first cause of disability in < 50s
affects 11% of the adults in the world
Slide3Introduction
Although much efforts have been made to elucidate migraine pathogenesis, its exact underlying mechanism remained to be understood.
To date, different mechanisms have been proposed,
such as:
Vascular dysfunction,
activation of the
trigeminovascular
system
neurogenic inflammation
Slide4Introduction
Neurogenic inflammation
Inflammation in the meningeDeveloping head pain in migraine.Activation of trigeminal nociceptors Release of vasoactive neuropeptides
Slide5Stress
Changes in hormone concentrations (especially Estrogen in females)
Cortical spreading depression (CSD) especially in migraine with aura
meningeal nociceptors’ activation
Introduction
Increasing the secretion of vasodilator neuropeptides in peripheral trigeminal afferents
Causing intra-cranial mast cells degranulation
Enhancing the release of pro-inflammatory factors.
Slide6CSD: cortical spreading depression, CGRP: calcitonin gene related peptide, NK-1: neurokinin 1, CLR: calcitonin-like receptor, RAMP1: receptor activity modulating protein 1, RCP: receptor component protein
Mechanistic hypothesis of neurogenic inflammation in the
dural vasculature
Slide7Neurogenic inflammation in Migraine
↑↑
inflammatory factors and
vasodilatory
neuropeptides:
IL-6, IL-1β, TNFα, SP, CGRP, NKA, Glutamate, serotonin, NO, COX enzymes, prostaglandins, NGF, PACAP and VIP in the CSF and plasma of migraine patients
↑
Release of HMGB1 and HSP70 during CSD
↑
Expression of TLR4 and NF-kB on primary afferent neurons, microglia, and astrocytes
Induce dilation of arteriescause plasma leakage trigger releasing the contents of mast cells
Activation of astrocytes, microglia, and mast cells, which under inflammatory conditions are able to pass the BBB.
Sensitization of trigeminal nociceptors and raising local inflammatory state
Slide8Increased glutamatergic transmission in migraine can induce and maintain the production and release of CGRP and SP causing vasodilation and plasma protein extravasation.
Serotonin, due to its nociceptive and vasoactive properties, has been long implicated in migraine pathophysiology.
There is substantial evidence for the role of NO in migraine that is a potent vasodilator which mediates its effect via CGRP and SP release from perivascular nociceptive afferents via signaling through MAP kinase pathwaysNO acts on dural vessels and contributes to the amplification of these afferent signals by enhancing the release of proinflammatory factors including CGRP leading to neurogenic inflammationInfluence of non-peptidergic molecules on mediating neurogenic inflammation
Slide9Neurogenic inflammation in Migraine
U
ndoubtedly, activatio
n
o
f
du
ral
afferents occurs
w
it
h
th
e
re
l
ea
s
e
o
f
C
G
RP
a
n
d
S
P.
T
hi
s
l
ea
d
s
t
o
pl
a
s
ma
prot
e
i
n
e
xt
ra
v
a
s
a
tio
n
a
n
d
re
l
ea
s
e
o
f
p
r
o
-
in
f
l
a
m
m
a
to
ry
c
y
tokin
es
ca
usin
g
st
er
il
e
in
f
l
amma
tion
.
Slide10CGRP
A potent vasodilator and is released from intracranial afferents during the course of migraine attack
SP A far less potent vasoactive molecule as compared to CGRP. Limited studies supportThough both CGRP and SP are released into the dural vasculature from the afferents, SP is the prime mediator in causing plasma protein leakage by acting on the NK-1 receptors expressed on the micro-vascular blood vesselsIt has been shown to be blocked by triptans and NSAIDs, selectively in the dura mater but not in the extracranial structures or in the brain or brain vasculatureKey characteristic of neurogenic inflammation in migraine
Vasodilation
Plasma protein extravasation
Slide11Activation
and degranulation
of mast cells via one of several pathways can release of a plethora of pro-nociceptive mediators:histamine, serotonin, pro-inflammatory cytokines (TNF-α, IL-1, and IL-6 ), kinins, and proteases that are stored in secretory granules Recent hypotheses state that mast cells can per se contribute to the sterile inflammatory state in the meninges thereby promoting sensitization of meningeal afferents, leading to orthograde traffic in trigeminal vascular afferents and local (meningeal) release of products such as SP and CGRP. Mast cell degranulationKey characteristic of neurogenic inflammation in migraine
Slide12Mechanistic hypothesis of neurogenic inflammation in the
dural
vasculatureActivated neuron injury signals release neurotransmitterwhich induce mast cell and microglia activation and release of proinflammatory cytokines/chemokines involved in migraine.
Slide13Drug therapy in migraine according to the hypothesis of neurogenic inflammation
One major aim in acute treatment of migraine is to have
pathophysiologically active drugs,Acute migraine treatment remains then bonded to triptans and NSAID use, with the well-known limits due to their side effects, cardiovascular for the first and GI for the latter.
Slide14Drug therapy in migraine according to the hypothesis of neurogenic inflammation
The new migraine treatment drugs
certainly interfere with signaling pathways of CGRP, a vasodilatory neuropeptide expressed in the cranial sensory nerves
and PACAP
, a parasympathetic vasodilator peptide that is linked to cranial autonomic symptoms in migraine.
Slide15Drug therapy in migraine according to the hypothesis of neurogenic inflammation
CGRP receptor antagonists, anti-CGRP antibodies and anti-CGRP receptor antibodies have proved effective for migraine pain relief, strongly supporting the hypothesis
that CGRP and the subsequent inflammatory state have a major role in migraine pathophysiology.
Slide16Conclusion
The current evidence emphasizes that the migraine pain phenotype reflects the anomalous activation of
trigeminovascular afferents projecting to the second order neurons in the brainstem and also indicates several contributing factors of neurogenic inflammation and suggests the involvement of neuroimmune interactions in mediating pain in migraine headache.
Slide17See the IHS website for more information
and to join online
Belong to the
International Headache Society (IHS)
Headache/neurology specialists from Iran can join
free of charge
as an Associate Member
Online access to
Cephalalgia
Online access to
The Neuroscientist
Access to the IHS Online Learning Centre
Early access to IHS International Guidelines
Benefit from key Exchange Programmes and Awards
Fellowships / Scholarships
Travel Grants
Visiting Professors
Headache Master Schools
www.ihs-headache.org
To advance headache science, education and management, and promote headache awareness worldwide
.
Free of charge
Associate Membership