Frontiers in Cellular Neuroscience,
Год журнала:
2020,
Номер
14
Опубликована: Апрель 15, 2020
Initially
developed
with
the
aim
of
generating
new
treatments
for
epilepsy,
gabapentin
and
pregabalin
("gabapentinoids")
were
engineered
to
mimic
action
GABA
modulate
metabolism.
Rather
than
their
intended
pharmacological
on
neurotransmission,
instead
they
exhibit
a
high
affinity
α2δ-1and
-2
subunits
voltage-activated
calcium
channels,
wherein
binding
gabapentinoids
inhibits
cellular
influx
attenuates
neurotransmission.
Despite
lack
activity
levels,
are
effective
at
suppressing
seizures
subsequently
approved
as
class
antiepileptic
therapy
partial-onset
epilepsy.
Through
same
hypothesized
molecular
mechanism
by
controlling
neuronal
hyperexcitability,
demonstrate
clear
efficacy
in
pain
management,
which
has
arguably
been
most
extensively
prescribed
application
date.
In
this
review,
we
focus
second-generation
gabapentinoid
widely
employed
treatment
variety
conditions.
We
also
discuss
wider
functional
roles
contributions
that
might
play
affecting
physiological
pathophysiological
processes.
Physiological Reviews,
Год журнала:
2020,
Номер
101(1), С. 259 - 301
Опубликована: Июнь 25, 2020
Neuropathic
pain
caused
by
a
lesion
or
disease
of
the
somatosensory
nervous
system
is
common
chronic
condition
with
major
impact
on
quality
life.
Examples
include
trigeminal
neuralgia,
painful
polyneuropathy,
postherpetic
and
central
poststroke
pain.
Most
patients
complain
an
ongoing
intermittent
spontaneous
of,
for
example,
burning,
pricking,
squeezing
quality,
which
may
be
accompanied
evoked
pain,
particular
to
light
touch
cold.
Ectopic
activity
in,
nerve-end
neuroma,
compressed
nerves
nerve
roots,
dorsal
root
ganglia,
thalamus
in
different
conditions
underlie
Evoked
spread
neighboring
areas,
underlying
pathophysiology
involves
peripheral
sensitization.
Maladaptive
structural
changes
number
cell-cell
interactions
molecular
signaling
sensitization
nociceptive
pathways.
These
alteration
ion
channels,
activation
immune
cells,
glial-derived
mediators,
epigenetic
regulation.
The
classes
therapeutics
drugs
acting
α
2
δ
subunits
calcium
sodium
descending
modulatory
inhibitory
Pharmacological Reviews,
Год журнала:
2018,
Номер
70(2), С. 315 - 347
Опубликована: Март 2, 2018
Injury
to
or
disease
of
the
nervous
system
can
invoke
chronic
and
sometimes
intractable
neuropathic
pain.
Many
parallel,
interdependent,
time-dependent
processes,
including
neuroimmune
interactions
at
peripheral,
supraspinal,
spinal
levels,
contribute
etiology
this
"disease
pain."
Recent
work
emphasizes
roles
colony-stimulating
factor
1,
ATP,
brain-derived
neurotrophic
factor.
Excitatory
processes
are
enhanced,
inhibitory
attenuated
in
dorsal
horn
throughout
somatosensory
system.
This
leads
central
sensitization
aberrant
processing
such
that
tactile
innocuous
thermal
information
is
perceived
as
pain
(allodynia).
Processes
involved
onset
differ
from
those
its
long-term
maintenance.
Opioids
display
limited
effectiveness,
less
than
35%
patients
derive
meaningful
benefit
other
therapeutic
approaches.
We
thus
review
promising
targets
have
emerged
over
last
20
years,
Na+,
K+,
Ca2+,
hyperpolarization-activated
cyclic
nucleotide–gated
channels,
transient
receptor
potential
channel
type
V1
adenosine
A3
receptors.
Despite
progress,
gabapentinoids
retain
their
status
first-line
treatments,
yet
mechanism
action
poorly
understood.
outline
recent
progress
understanding
show
how
has
provided
insights
into
cellular
actions
pregabalin
gabapentin.
Interactions
with
α2δ-1
subunit
voltage-gated
Ca2+
channels
produce
multiple
neuron
type-specific
cord
higher
centers.
suggest
drugs
affect
rather
a
single
specific
target,
greatest
promise
for
future
development.
Science,
Год журнала:
2019,
Номер
363(6424), С. 276 - 281
Опубликована: Янв. 18, 2019
The
emotional
dimension
of
pain
unpleasantness
is
an
phenomenon
distinct
from
pain's
sensory
qualities.
To
study
how
the
brain
processes
pain-related
emotions,
Corder
et
al.
used
in
vivo
neural
calcium
imaging
freely
behaving
mice.
They
identified
circuits
that
respond
to
and
directly
tested
their
causal
role
motivational
behaviors
associated
with
acute
chronic
pain.
Science
,
this
issue
p.
276
