Migraine
has
a
strong
genetic
foundation,
including
both
monogenic
and
polygenic
types.
The
former
are
rare,
with
most
migraine
considered
polygenic,
supported
by
genome-wide
association
studies
(GWAS)
identifying
numerous
variants
associated
risk.
Surprisingly,
some
of
the
common
mutations
TRPM8,
non-selective
cation
channel
that
is
primary
sensor
cold
temperatures
in
afferent
neurons
somatosensory
system.
However,
it
unlikely
temperature
sensitivity
TRPM8
underlies
its
role
pathogenesis.
To
define
basis
channel's
involvement,
we
reasoned
cellular
processes
increase
skin,
such
as
neurotrophin
artemin,
via
receptor
GFRα3,
also
mediate
TRPM8-associated
migraine-like
pain
meninges.
Neuroscience & Biobehavioral Reviews,
Journal Year:
2024,
Volume and Issue:
163, P. 105749 - 105749
Published: June 3, 2024
The
introduction
of
sex-as-a-biological-variable
policies
at
funding
agencies
around
the
world
has
led
to
an
explosion
very
recent
observations
sex
differences
in
biology
underlying
pain.
This
review
considers
evidence
sexually
dimorphic
mechanisms
mediating
pain
hypersensitivity,
derived
from
modern
assays
persistent
rodent
animal
models.
Three
well-studied
findings
are
described
detail:
male-specific
role
spinal
cord
microglia,
female-specific
calcitonin
gene-related
peptide
(CGRP),
and
prolactin
its
receptor.
Other
sex-specific
molecular
involvement
subjected
pathway
analyses
reveal
least
one
novel
hypothesis:
that
females
may
preferentially
use
Th1
males
Th2
T
cell
activity
mediate
chronic
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(3), P. 1771 - 1771
Published: Feb. 1, 2024
Neuropathic
pain,
which
is
initiated
by
a
malfunction
of
the
somatosensory
cortex
system,
elicits
inflammation
and
simultaneously
activates
glial
cells
that
initiate
neuroinflammation.
Electroacupuncture
(EA)
has
been
shown
to
have
therapeutic
effects
for
neuropathic
although
with
uncertain
mechanisms.
We
suggest
EA
can
reliably
cure
disease
through
anti-inflammation
transient
receptor
potential
V1
(TRPV1)
signaling
pathways
from
peripheral
central
nervous
system.
To
explore
this,
we
used
treat
mice
spared
nerve
injury
(SNI)
model
underlying
molecular
mechanisms
novel
chemogenetics
techniques.
Both
mechanical
thermal
pain
were
found
in
SNI
at
four
weeks
(mechanical:
3.23
±
0.29
g;
thermal:
4.9
0.14
s).
Mechanical
hyperalgesia
was
partially
attenuated
2
Hz
4.05
0.19
g),
fully
reduced
(thermal:
6.22
0.26
s)
but
not
sham
3.13
0.23
4.58
0.37
s),
suggesting
EA’s
specificity.
In
addition,
animals
Trpv1
deletion
showed
partial
no
significant
induction
4.43
6.24
0.09
Moreover,
increased
levels
inflammatory
factors
such
as
interleukin-1
beta
(IL1-β),
IL-3,
IL-6,
IL-12,
IL-17,
tumor
necrosis
factor
alpha,
interferon
gamma
after
modeling,
decreased
Trpv1−/−
groups
rather
than
group.
Western
blot
immunofluorescence
analysis
similar
tendencies
dorsal
root
ganglion,
spinal
cord
horn,
(SSC),
anterior
cingulate
(ACC).
method
precisely
inhibit
SSC
ACC
activity,
an
analgesic
effect
TRPV1
pathway.
summary,
our
findings
indicate
mechanism
beneficial
target
pain.
Frontiers in Immunology,
Journal Year:
2025,
Volume and Issue:
16
Published: April 8, 2025
Diabetic
neuropathic
pain
(DNP)
is
one
of
the
most
prevalent
complications
diabetes,
characterized
by
a
high
global
prevalence
and
substantial
affected
population
with
limited
effective
therapeutic
options.
Although
DNP
closely
associated
hyperglycemia,
an
increasing
body
research
suggests
that
elevated
blood
glucose
levels
are
not
sole
inducers
DNP.
The
pathogenesis
intricate,
involving
release
inflammatory
mediators,
alterations
in
synaptic
plasticity,
demyelination
nerve
fibers,
ectopic
impulse
generation,
yet
precise
mechanisms
remain
to
be
elucidated.
spinal
dorsal
horn
coordinates
dynamic
interactions
between
peripheral
central
pathways,
wherein
neurons,
microglia,
astrocytes
synergize
Schwann
cell-derived
signals
process
nociceptive
information
flow.
Abnormally
activated
neurons
can
alter
signal
transduction
modifying
local
microenvironment,
compromising
myelin
integrity,
diminishing
trophic
support,
leading
neuronal
sensitization
amplifying
effect
on
signals,
which
turn
triggers
pain.
Ion
channels
play
pivotal
role
conduction,
modulation
sodium,
potassium,
calcium
being
particularly
crucial
for
regulation
signals.
In
light
rising
incidence
diabetes
current
scarcity
treatments,
thorough
investigation
into
glial
cells,
especially
ion
channel
function
DNP,
imperative
identifying
potential
drug
targets,
developing
novel
strategies,
thereby
enhancing
prospects
management.
International Journal of Cosmetic Science,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 13, 2025
Abstract
Objective
The
study
investigated
effects
of
peony
callus
extracts
(PCE)
on
the
protective
efficacy
against
Ultraviolet
B
(UVB)‐induced
photoageing,
using
in
vitro
and
vivo
studies.
research
focused
PCE's
ability
to
protect
inflammatory
factors,
DNA
damage
accumulation
senescent
cells,
along
with
evaluation
extract's
potential
anti‐photoageing
benefits
skin.
Methods
Human
keratinocyte
cell
line
(HaCaT
cells),
mast
cells
fibroblasts
were
used
evaluate
role
PCE
anti‐photoageing.
expression
genes
interleukin‐1α
(IL‐1α)
,
IL‐6
transient
receptor
vanilloid
1
(
TRPV1
)
tested
HaCaT
cells.
histamine
contents
effect
soothing
Additionally,
repairment
stimulated
by
UVB
comet
assay
was
evaluated.
In
fibroblasts,
gene
matrix
metalloproteinases
MMPs
activity
β‐galactosidase
tested.
test,
13
healthy
volunteers
enrolled
apply
a
formula
1%
assess
variation
inner
skin
collagen
contents.
Results
from
an
ancient
rare
variety
tree
Paeoniaceae
family)
successfully
induced,
its
ingredients
extracted.
could
significantly
downregulate
inflammation
factors
such
as
IL‐1α
which
cause
degradation
induced
UVB.
Meanwhile,
UVB‐induced
alleviated
PCE.
analysis
content
revealed
that
effectively
sensitivity.
Furthermore,
clinical
trials
validated
significant
increase
total
vivo,
following
28
days
continuous
application
cosmetic
formulation
containing
measured
Raman
confocal
spectroscopy
technology.
Conclusion
indicating
repair.
number
also
decreased
after
stimulation.
results
showed
ideal
ingredient
for
promoting
levels.
Neurobiology of Pain,
Journal Year:
2024,
Volume and Issue:
15, P. 100155 - 100155
Published: Jan. 1, 2024
Thermosensation,
the
ability
to
detect
and
estimate
temperature,
is
an
evolutionarily
conserved
process
that
essential
for
survival.
Thermosensing
impaired
in
various
pain
syndromes,
resulting
thermal
allodynia,
perception
of
innocuous
temperature
as
painful,
or
hyperalgesia,
exacerbated
a
painful
stimulus.
Several
behavioral
assays
exist
study
thermosensation
rodents,
however,
most
rely
on
reflexive
withdrawal
responses
subjective
quantification
spontaneous
nocifensive
behaviors.
Here,
we
created
new
apparatus,
escape
box,
which
can
be
attached
temperature-controlled
plates
used
assess
temperature-dependent
effort-based
decision-making.
The
apparatus
consists
light
chamber
with
opening
fits
around
plates,
small
entryway
into
dark
chamber.
A
mouse
must
choose
stay
brightly
lit
aversive
area
traverse
enclosed
We
quantified
latencies
adult
C57Bl/6
mice
at
different
plate
temperatures
from
video
recordings
found
they
were
significantly
longer
5
°C,
18
52
compared
30
mouse's
preferred
ambient
temperature.
Differences
abolished
male
Trpm8−/−
Trpv1−/−
animals.
Finally,
show
chronic
constriction
injury
procedures
oxaliplatin
treatement
increased
cold
controls,
later
was
prevented
by
analgesic
meloxicam.
This
demonstrates
utility
this
assay
detecting
pain.
Collectively,
our
has
identified
effective
tool
uses
cost-benefit
valuations
Frontiers in Physiology,
Journal Year:
2024,
Volume and Issue:
15
Published: July 3, 2024
The
transient
receptor
potential
ankyrin
1
(TRPA1)
channel
plays
a
pivotal
role
in
the
respiratory
and
gastrointestinal
tracts.
Within
system,
TRPA1
exhibits
diverse
distribution
patterns
across
key
cell
types,
including
epithelial
cells,
sensory
nerves,
immune
cells.
Its
activation
serves
as
frontline
sensor
for
inhaled
irritants,
triggering
immediate
protective
responses,
influencing
airway
integrity.
Furthermore,
has
been
implicated
tissue
injury,
inflammation,
transition
of
fibroblasts,
thereby
posing
challenges
conditions,
such
severe
asthma
fibrosis.
In
contributes
to
nociception,
cough
reflex,
bronchoconstriction,
highlighting
its
both
defense
mechanisms
long-term
reflex
arcs.
may
modulate
release
pro-inflammatory
mediators,
shaping
overall
inflammatory
landscape.
tract,
dynamic
expression
enteric
neurons,
cells
underscores
multifaceted
involvement.
It
crucial
gut
motility,
visceral
pain
perception,
mucosal
mechanisms.
Dysregulation
tracts
is
associated
with
various
disorders
asthma,
Chronic
Obstructive
Pulmonary
Disease,
Irritable
Bowel
Syndrome,
Inflammatory
Disease.
This
review
emphasizes
therapeutic
target
discusses
efficacy
antagonists
preclinical
studies
their
promise
addressing
conditions.
Understanding
intricate
interactions
cross-talk
different
types
provides
insight
into
versatile
maintaining
homeostasis
vital
physiological
systems,
offering
foundation
targeted
interventions.
The Journal of General Physiology,
Journal Year:
2024,
Volume and Issue:
156(10)
Published: July 25, 2024
Thermosensation
requires
the
activation
of
a
unique
collection
ion
channels
and
receptors
that
work
in
concert
to
transmit
thermal
information.
It
is
widely
accepted
transient
receptor
potential
melastatin
8
(TRPM8)
required
for
normal
cold
sensing;
however,
recent
studies
have
illuminated
major
roles
other
this
important
somatic
sensation.
In
addition
TRPM8,
TRP
been
reported
contribute
transduction
mechanisms
diverse
sensory
neuron
populations,
with
both
leak-
voltage-gated
being
identified
their
role
transmission
signals.
Whether
same
physiological
sensing
also
mediate
noxious
signaling
remains
unclear;
has
found
conserved
kainite
receptor,
GluK2,
across
species.
Additionally,
cold-sensing
neurons
likely
engage
functional
crosstalk
nociceptors
give
rise
pain.
This
Review
will
provide
an
update
on
our
understanding
relationship
between
various
highlight
areas
where
further
investigation
required.
Cephalalgia,
Journal Year:
2024,
Volume and Issue:
44(11)
Published: Nov. 1, 2024
Background
Migraine
has
a
strong
genetic
foundation,
including
both
monogenic
and
polygenic
types.
The
former
are
rare,
with
most
migraine
considered
polygenic,
supported
by
genome-wide
association
studies
(GWAS)
identifying
numerous
variants
linked
risk.
Surprisingly,
some
of
the
common
mutations
associated
transient
receptor
potential
melastatin
8
(TRPM8),
non-selective
cation
channel
that
is
primary
sensor
cold
temperatures
in
cutaneous
afferents
somatosensory
system.
However,
it
unlikely
temperature
sensitivity
TRPM8
relevant
migraine-related
tissues,
such
as
meninges,
suggesting
other
activation
mechanisms
underly
its
role
pathogenesis.
Thus,
to
define
basis
channel's
involvement,
we
reasoned
cellular
processes
increase
skin,
neurotrophic
factor
artemin,
via
glial
cell-line
derived
family
alpha-3
(GFRα3),
also
mediate
TRPM8-associated
migraine-like
pain
meninges.
Methods
To
investigate
artemin
GFRα3
preclinical
rodent
models,
infused
nitroglycerin
acutely
chronically,
measured
changes
periorbital
hind
paw
mechanical
male
female
mice
lacking
GFRα3,
after
neutralization
free
specific
monoclonal
antibodies,
or
systemic
treatment
TRPM8-specific
antagonist.
Further,
tested
effects
supradural
infusions
mix
inflammatory
mediators,
well
if
dura
stimulation
agonist
induce
mice.
Results
We
find
allodynia
induced
nitroglycerin,
infusion
involves
GFRα3.
In
addition,
circulating
reduces
phenotype,
demonstrating
importance
this
pathway
headaches.
show
expression
direct
either
itself
produces
allodynia,
latter
dependent
on
ameliorated
concurrent
sumatriptan.
Conclusions
These
results
indicate
neuroinflammatory
events
meninges
can
produce
likely
acting
upstream
TRPM8,
providing
novel
may
contribute
headaches
