Life,
Год журнала:
2025,
Номер
15(6), С. 888 - 888
Опубликована: Май 30, 2025
Neuropathic
pain
is
a
chronic
and
debilitating
disorder
of
the
somatosensory
system
that
affects
significant
proportion
population
characterized
by
abnormal
responses
such
as
hyperalgesia
allodynia.
Voltage-gated
ion
channels,
including
sodium
(NaV),
calcium
(CaV),
potassium
(KV)
play
pivotal
role
in
modulating
neuronal
excitability
signal
transmission
following
nerve
injury.
This
review
intends
to
provide
comprehensive
analysis
molecular
cellular
mechanisms
which
dysregulation
expression,
localization,
function
specific
NaV
channel
subtypes
(mainly
NaV1.7
NaV1.8)
their
auxiliary
subunits
contributes
aberrant
activation,
generation
ectopic
discharges,
sensitization
neuropathic
pain.
Likewise,
special
emphasis
placed
on
crucial
CaV
particularly
CaV2.2
subunit
CaVα2δ,
whose
overexpression
increases
influx,
neurotransmitter
release,
hyperexcitability,
thus
maintaining
persistent
states.
Furthermore,
KV
channels
(particularly
KV7
channels)
brakes
excitability,
facilitates
development
maintenance
Therefore,
targeting
restore
also
promising
therapeutic
strategy
for
alleviating
symptoms.
On
other
hand,
recent
advances
small
molecules
selective
modulators
or
inhibitors
voltage-gated
are
discussed.
These
agents
have
improved
efficacy
safety
profiles
preclinical
clinical
studies
attenuating
pathophysiological
activity
restoring
function.
seeks
contribute
guiding
future
research
drug
toward
more
effective
mechanism-based
treatments
discussing
underlying
highlighting
translational
opportunities.
The Journal of General Physiology,
Год журнала:
2025,
Номер
157(4)
Опубликована: Март 26, 2025
Nav1.8
sodium
channels
are
expressed
in
pain-sensing
neurons,
and
some
inhibitors
significantly
reduce
pain
clinical
trials.
Several
have
an
unusual
state
dependence
whereby
inhibition
is
relieved
by
depolarization.
We
compared
the
state-dependent
action
of
several
channel
to
test
whether
during
potential
(AP)
firing
under
physiological
conditions
produce
“reverse
use
dependence.”
A-887826
was
substantially
AP
waveforms
applied
at
20
Hz
37°C.
In
contrast,
there
no
relief
trains
with
suzetrigine
(VX-548)
or
LTGO-33,
even
though
could
be
effectively
removed
long,
strong
depolarizations.
These
differences
were
explained
voltage
kinetics
which
compounds
dissociate
from
depolarized
rebind
resting
channels.
Suzetrigine
required
strongest
depolarizations
for
(midpoint
+33
mV)
slow
(tau
>300
ms
+20
mV),
so
almost
occurred
waveform.
Relief
weaker
+13
much
faster,
each
waveform
accumulated
20-Hz
trains.
LTGO-33
weakest
−11
faster
than
A-887826,
but
reinhibition
between
far
that
did
not
accumulate
Hz.
The
results
show
that,
unlike
use-dependent
temperatures,
different
reasons.
The Journal of General Physiology,
Год журнала:
2025,
Номер
157(4)
Опубликована: Апрель 28, 2025
Voltage-gated
sodium
channels
underpin
electrical
signaling
in
sensory
neurons.
Their
activity
is
an
essential
element
the
vast
majority
of
pain
conditions,
making
them
significant
drug
targets.
Sensory
neuron
play
roles
not
only
afferent
but
also
a
range
efferent
regulatory
mechanisms.
Side
effects
through
actions
on
other
cell
types
and
are
thus
important
issues
to
address
during
analgesic
development.
As
example,
human
genetic
evidence
for
NaV1.7
as
ideal
target
contrasts
with
side
antagonists.
In
this
review,
we
describe
history
progress
toward
development
useful
drugs
renewed
focus
NaV1.8
key
treatment.
antagonists
alone
or
combination
analgesics
likely
provide
new
opportunities
relief
number
people
(about
33%
population)
impacted
by
chronic
pain,
particularly
present
aging
populations.
Pharmaceuticals,
Год журнала:
2025,
Номер
18(3), С. 386 - 386
Опубликована: Март 8, 2025
The
neurological
effects
of
opium
were
first
described
over
8000
years
ago.
Morphine
was
isolated
in
1803
and
by
the
mid-1800s
had
become
both
a
pain-relieving
blessing
an
addictive
curse.
As
part
crusade
to
identify
safer
more
reliable
alternatives
morphine,
dezocine
(Dalgan®)
marketed
US
1986.
Its
use
discontinued
2011
without
revealing
reasons,
but
it
remains
one
most
widely
used
analgesic
agents
China
today.
Dezocine’s
unique
pharmacology
makes
effective
with
limited
opioid-associated
side
little
or
no
reported
potential
for
dependence
addiction.
In
addition,
dezocine’s
blocking
effect
on
serotonin
norepinephrine
transporters
recommends
its
further
exploration
as
treatment
various
chronic
neuropathic
pain
conditions.
Most
recently,
data
suggest
that
might
represent
viable
addiction
management.
This
report
focuses
supporting
non-addictive
profile
treat
opioid
withdrawal,
well
recent
efforts
generate
formulations
support
sub-chronic
dosing.
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Апрель 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.
