PLoS Biology,
Journal Year:
2021,
Volume and Issue:
19(7), P. e3001337 - e3001337
Published: July 22, 2021
Peripheral
nerve
injury–induced
mechanical
allodynia
is
often
accompanied
by
abnormalities
in
the
higher
cortical
regions,
yet
mechanisms
underlying
such
maladaptive
plasticity
remain
unclear.
Here,
we
show
that
male
mice,
structural
and
functional
changes
primary
somatosensory
cortex
(S1)
caused
peripheral
injury
require
neuron-microglial
signaling
within
local
circuit.
Following
injury,
microglia
S1
maintain
ramified
morphology
normal
density
but
up-regulate
mRNA
expression
of
brain-derived
neurotrophic
factor
(BDNF).
Using
vivo
two-photon
imaging
Cx3cr1
CreER
;
Bdnf
flox
conditional
knockout
BDNF
from
prevents
synaptic
remodeling
pyramidal
neuron
hyperactivity
S1,
as
well
pain
hypersensitivity
mice.
Importantly,
S1-targeted
removal
microglial
largely
recapitulates
beneficial
effects
systemic
depletion
on
allodynia.
Together,
these
findings
reveal
a
pivotal
role
cerebral
hypersensitivity.
Physiological Reviews,
Journal Year:
2020,
Volume and Issue:
101(1), P. 259 - 301
Published: June 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
Nature Communications,
Journal Year:
2021,
Volume and Issue:
12(1)
Published: Sept. 29, 2021
Abstract
Single-cell
RNA
sequencing
data
can
unveil
the
molecular
diversity
of
cell
types.
Cell
type
atlases
mouse
spinal
cord
have
been
published
in
recent
years
but
not
integrated
together.
Here,
we
generate
an
atlas
types
based
on
single-cell
transcriptomic
data,
unifying
available
datasets
into
a
common
reference
framework.
We
report
hierarchical
structure
postnatal
relationships,
with
location
providing
highest
level
organization,
then
neurotransmitter
status,
family,
and
finally,
dozens
refined
populations.
validate
combinatorial
marker
code
for
each
neuronal
map
their
spatial
distributions
adult
cord.
also
show
complex
lineage
relationships
among
Additionally,
develop
open-source
classifier,
SeqSeek,
to
facilitate
standardization
identification.
This
work
provides
view
types,
gene
expression
signatures,
organization.
Nature,
Journal Year:
2022,
Volume and Issue:
606(7912), P. 137 - 145
Published: May 25, 2022
Abstract
Nerve
injury
leads
to
chronic
pain
and
exaggerated
sensitivity
gentle
touch
(allodynia)
as
well
a
loss
of
sensation
in
the
areas
which
injured
non-injured
nerves
come
together
1–3
.
The
mechanisms
that
disambiguate
these
mixed
paradoxical
symptoms
are
unknown.
Here
we
longitudinally
non-invasively
imaged
genetically
labelled
populations
fibres
sense
noxious
stimuli
(nociceptors)
(low-threshold
afferents)
peripherally
skin
for
longer
than
10
months
after
nerve
injury,
while
simultaneously
tracking
pain-related
behaviour
same
mice.
Fully
denervated
initially
lost
sensation,
gradually
recovered
normal
developed
marked
allodynia
aversion
several
injury.
This
reinnervation-induced
neuropathic
involved
nociceptors
sprouted
into
territories
precisely
reproducing
initial
pattern
innervation,
were
guided
by
blood
vessels
showed
irregular
terminal
connectivity
lowered
activation
thresholds
mimicking
low-threshold
afferents.
By
contrast,
afferents—which
normally
mediate
intact
4–7
—did
not
reinnervate,
leading
an
aberrant
innervation
tactile
end
organs
such
Meissner
corpuscles
with
alone.
Genetic
ablation
fully
abrogated
reinnervation
allodynia.
Our
results
thus
reveal
emergence
form
is
driven
structural
plasticity,
abnormal
malfunction
during
reinnervation,
provide
mechanistic
framework
sensory
manifestations
observed
clinically
can
impose
heavy
burden
on
patients.
Science,
Journal Year:
2022,
Volume and Issue:
377(6602), P. 198 - 204
Published: July 7, 2022
Sound-including
music
and
noise-can
relieve
pain
in
humans,
but
the
underlying
neural
mechanisms
remain
unknown.
We
discovered
that
analgesic
effects
of
sound
depended
on
a
low
(5-decibel)
signal-to-noise
ratio
(SNR)
relative
to
ambient
noise
mice.
Viral
tracing,
microendoscopic
calcium
imaging,
multitetrode
recordings
freely
moving
mice
showed
low-SNR
sounds
inhibited
glutamatergic
inputs
from
auditory
cortex
(ACxGlu)
thalamic
posterior
(PO)
ventral
(VP)
nuclei.
Optogenetic
or
chemogenetic
inhibition
ACxGlu→PO
ACxGlu→VP
circuits
mimicked
sound-induced
analgesia
inflamed
hindpaws
forepaws,
respectively.
Artificial
activation
these
two
abolished
analgesia.
Our
study
reveals
corticothalamic
sound-promoted
by
deciphering
role
system
processing.