The Journal of Physiological Sciences,
Journal Year:
2024,
Volume and Issue:
74(1)
Published: June 14, 2024
The
volume-sensitive
outwardly
rectifying
or
volume-regulated
anion
channel,
VSOR/VRAC,
which
was
discovered
in
1988,
is
expressed
most
vertebrate
cell
types,
and
essentially
involved
volume
regulation
after
swelling
the
induction
of
death.
This
series
review
articles
describes
what
already
known
remains
to
be
uncovered
about
functional
molecular
properties
as
well
physiological
pathophysiological
roles
VSOR/VRAC.
Part
2
article
describes,
from
standpoints,
first
pivotal
VSOR/VRAC
release
autocrine/paracrine
organic
signal
molecules,
such
glutamate,
ATP,
glutathione,
cGAMP,
itaconate,
second
swelling-independent
-dependent
activation
mechanisms
Since
pore
size
has
now
been
evaluated
by
electrophysiological
3D-structural
methods,
signal-releasing
activity
here
discussed
comparing
sizes
these
signals
channel
size.
Swelling-independent
include
a
physicochemical
one
caused
reduction
intracellular
ionic
strength
biochemical
oxidation
due
stimulation
receptor
agonists
apoptosis
inducers.
Because
some
substances
released
via
upon
can
trigger
augment
an
autocrine
fashion,
swelling-dependent
are
divided
into
two
phases:
phase
induced
per
se
signals.
Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: June 8, 2024
Abstract
Pain
is
estimated
to
affect
more
than
20%
of
the
global
population,
imposing
incalculable
health
and
economic
burdens.
Effective
pain
management
crucial
for
individuals
suffering
from
pain.
However,
current
methods
assessment
treatment
fall
short
clinical
needs.
Benefiting
advances
in
neuroscience
biotechnology,
neuronal
circuits
molecular
mechanisms
critically
involved
modulation
have
been
elucidated.
These
research
achievements
incited
progress
identifying
new
diagnostic
therapeutic
targets.
In
this
review,
we
first
introduce
fundamental
knowledge
about
pain,
setting
stage
subsequent
contents.
The
review
next
delves
into
underlying
disorders,
including
gene
mutation,
epigenetic
modification,
posttranslational
inflammasome,
signaling
pathways
microbiota.
To
better
present
a
comprehensive
view
research,
two
prominent
issues,
sexual
dimorphism
comorbidities,
are
discussed
detail
based
on
findings.
status
quo
evaluation
manipulation
summarized.
A
series
improved
innovative
strategies,
such
as
therapy,
monoclonal
antibody,
brain-computer
interface
microbial
intervention,
making
strides
towards
application.
We
highlight
existing
limitations
future
directions
enhancing
quality
preclinical
research.
Efforts
decipher
complexities
pathology
will
be
instrumental
translating
scientific
discoveries
practice,
thereby
improving
bench
bedside.
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
Frontiers in Pain Research,
Journal Year:
2023,
Volume and Issue:
4
Published: Sept. 22, 2023
Neuropathic
pain
can
result
from
injury
to,
or
disease
of
the
nervous
system.
It
is
notoriously
difficult
to
treat.
Peripheral
nerve
promotes
Schwann
cell
activation
and
invasion
immunocompetent
cells
into
site
injury,
spinal
cord
higher
sensory
structures
such
as
thalamus
cingulate
cortices.
Various
cytokines,
chemokines,
growth
factors,
monoamines
neuropeptides
effect
two-way
signalling
between
neurons,
glia
immune
cells.
This
sustained
hyperexcitability
spontaneous
activity
in
primary
afferents
that
crucial
for
onset
persistence
well
misprocessing
information
supraspinal
structures.
Much
current
understanding
aetiology
identification
drug
targets
derives
studies
consequences
peripheral
rodent
models.
Although
a
vast
amount
has
been
forthcoming,
translation
this
clinical
arena
minimal.
Few,
if
any,
major
therapeutic
approaches
have
appeared
since
mid
1990's.
may
reflect
failure
recognise
differences
processing
males
vs.
females,
cellular
responses
different
types
humans
animals.
Basic
science
which
seek
bridge
knowledge
gap
include
better
assessment
animal
models,
use
models
emulate
human
disease,
stratification
phenotypes
according
quantitative
signs
symptoms
disease.
lead
more
personalized
effective
treatments
individual
patients.
Significance
statement:
There
an
urgent
need
find
new
neuropathic
pain.
classical
revealed
essential
features
central
sensitization
some
molecular
mechanisms
involved,
they
do
not
adequately
model
multiplicity
states
injuries
bring
forth
clinic.
review
seeks
integrate
disciplines
understand
pain;
including
immunology,
biology,
electrophysiology
biophysics,
anatomy,
neurology,
pharmacology
behavioral
science.
Beyond
this,
it
underlines
ongoing
refinements
basic
practice
will
engender
improved
management.
Frontiers in Cell and Developmental Biology,
Journal Year:
2024,
Volume and Issue:
11
Published: Jan. 18, 2024
Extracellular
ATP
and
adenosine
are
neuromodulators
that
regulate
numerous
neuronal
functions
in
the
brain.
Neuronal
activity
brain
insults
such
as
ischemic
traumatic
injury
upregulate
these
neuromodulators,
which
exert
their
effects
by
activating
purinergic
receptors.
In
addition,
extracellular
ATP/adenosine
signaling
plays
a
pivotal
role
pathogenesis
of
neurological
diseases.
Virtually
every
cell
type
contributes
to
elevation
ATP/adenosine,
various
mechanisms
underlying
this
increase
have
been
proposed.
is
thought
be
mainly
produced
via
degradation
ATP.
However,
also
released
from
neurons
glia
Therefore,
regulation
physiological
pathophysiological
conditions
likely
far
more
complex
than
previously
thought.
To
elucidate
levels,
accurate
methods
assessing
spatiotemporal
dynamics
needed.
Several
novel
techniques
for
acquiring
information
on
including
fluorescent
sensors,
developed
started
reveal
release,
uptake
ATP/adenosine.
Here,
we
review
analyzing
well
current
state
knowledge
We
focus
used
cooperatively
produce
activity-dependent
its
significance
Cell & Bioscience,
Journal Year:
2025,
Volume and Issue:
15(1)
Published: Jan. 9, 2025
Abstract
Background
Neuropathic
pain
resulting
from
spinal
cord
injury
(SCI)
is
associated
with
persistent
hyperactivity
of
primary
nociceptors.
Anandamide
(AEA)
has
been
reported
to
modulate
neuronal
excitability
and
synaptic
transmission
through
activation
cannabinoid
type-1
receptors
(CB1Rs)
transient
receptor
potential
vanilloid
1
(TRPV1).
However,
the
role
AEA
these
in
nociceptors
after
SCI
remains
unclear.
Results
In
this
study,
we
investigated
effects
its
on
hyperexcitability
mouse
dorsal
root
ganglion
(DRG)
neurons
SCI.
Using
a
whole-cell
patch-clamp
technique,
found
that
timing
SCI-induced
paralleled
an
increase
endocannabinoid
content.
The
expression
TRPV1
CB1R
was
also
upregulated
at
different
time
points
High-dose
extracellular
administration
increased
naive
DRG
neurons,
leading
transition
rapidly
accommodating
(RA)
hypoexcitable
state
highly
excitable
non-accommodating
(NA)
state.
These
AEA-induced
transitions
were
facilitated
by
transcription.
Pharmacological
Ca
2+
imaging
experiments
revealed
induced
via
AEA-TRPV1-Ca
pathway,
whereas
CB1Rs
reduced
maintained
cytosolic
concentration
([Ca
]
cyto
)
low
levels
early
stages
As
SCI,
adaptive
neuroprotection
transitioned
maladaptive
hyperactive
state,
sustained
pain.
Conclusions
Taken
together,
study
provides
new
insights
into
how
endocannabinoids
regulate
nociceptor
activity
offering
targets
for
treatment
neuropathic
Frontiers in Pain Research,
Journal Year:
2025,
Volume and Issue:
6
Published: Feb. 18, 2025
Phantom
limb
pain
(PLP)
is
defined
as
the
perception
of
in
a
that
has
been
amputated.
In
United
States,
approximately
30,000-40,000
amputations
are
performed
annually
with
an
estimated
2.3
million
people
living
amputations.
The
prevalence
PLP
among
amputees
64%.
Over
years,
various
theories
regarding
etiology
have
proposed,
some
gaining
more
prominence
than
others.
Yet,
there
lack
consensus
on
mechanisms
current
literature
exploring
pathophysiology
multifactorial,
involving
complex
interactions
between
central
and
peripheral
nervous
systems,
psychosocial
factors,
genetic
influences.
This
review
seeks
to
enhance
understanding
by
its
multifaceted
pathophysiology,
including
predispositions.
We
highlight
historical
aspects
PLP,
examining
how
these
expanded
include
dimensions
associated
chronic
amputees.
Additionally,
we
present
significant
findings
from
both
human
animal
studies
focused
neuroaxial
systems
recent
advances
molecular
research
further
elucidate
multifactorial
nature
PLP.
Ultimately,
hope
integration
theoretical
frameworks
will
lay
robust
foundation
for
future
Frontiers in Endocrinology,
Journal Year:
2023,
Volume and Issue:
14
Published: Oct. 6, 2023
Sphingolipids,
as
members
of
the
large
lipid
family,
are
important
components
plasma
membrane.
Sphingolipids
participate
in
biological
signal
transduction
to
regulate
various
physiological
processes
such
cell
growth,
apoptosis,
senescence,
and
differentiation.
Numerous
studies
have
demonstrated
that
sphingolipids
strongly
associated
with
glucose
metabolism
insulin
resistance.
Insulin
resistance,
including
peripheral
resistance
brain
is
closely
related
occurrence
development
many
metabolic
diseases.
In
addition
diseases,
like
type
2
diabetes,
also
involved
progression
neurodegenerative
diseases
Alzheimer’s
disease
Parkinson’s
disease.
However,
specific
mechanism
has
not
been
systematically
summarized.
This
article
reviews
involvement
highlighting
role
molecular
sphingolipid
cognitive
dysfunctions
neuropathological
abnormalities
brain.
