SSRN Electronic Journal,
Год журнала:
2022,
Номер
unknown
Опубликована: Янв. 1, 2022
Although
itch
and
pain
have
many
similarities,
they
are
completely
different
in
perceptual
experience
behavioral
response.
In
recent
years,
we
a
deep
understanding
of
the
neural
pathways
sensation
transmission.
However,
there
few
reports
on
role
non-neuronal
cells
itch.
Microglia
known
to
play
key
chronic
neuropathic
acute
inflammatory
pain.
It
is
still
unknown
whether
microglia
also
involved
regulating
transmission
sensation.
present
study,
used
several
kinds
transgenic
mice
specifically
deplete
CX3CR1+
central
peripheral
macrophages
together
(whole
depletion),
or
selectively
alone
(central
depletion).
We
observed
that
responses
histamine,
compound
48/80
chloroquine
were
all
significantly
reduced
with
either
whole
depletion.
Spinal
c-fos
mRNA
assay
further
studies
revealed
histamine
48/80,
but
not
elicited
primary
signal
from
DRG
spinal
npr1-
somatostatin-positive
neurons
relied
microglial
CX3CL1-CX3CR1
pathway.
Our
results
indicated
multiple
types
chemical
transmission,
while
underlying
mechanisms
for
dependent
non-dependent
former
required
pathway.Funding
Information:
This
work
was
supported
by
Jiangxi
Province
“2000
talent
plan”
JP
(jxsq2018106039)
National
Natural
Science
Foundation
China
(32060199
J.P.,
82071245
H.P.,
81471116,
31771182
B.M.L.).Declaration
Interests:
The
authors
declare
no
competing
interests.Ethics
Approval
Statement:
All
experimental
procedures
approved
Institutional
Animal
Care
Use
Committee
Nanchang
University.
followed
guidelines
set
forth
Guide
Laboratory
Animals
8th
Edition.
Cell,
Год журнала:
2024,
Номер
187(6), С. 1508 - 1526.e16
Опубликована: Март 1, 2024
Dorsal
root
ganglia
(DRG)
somatosensory
neurons
detect
mechanical,
thermal,
and
chemical
stimuli
acting
on
the
body.
Achieving
a
holistic
view
of
how
different
DRG
neuron
subtypes
relay
neural
signals
from
periphery
to
CNS
has
been
challenging
with
existing
tools.
Here,
we
develop
curate
mouse
genetic
toolkit
that
allows
for
interrogating
properties
functions
distinct
cutaneous
targeting
subtypes.
These
tools
have
enabled
broad
morphological
analysis,
which
revealed
axon
arborization
areas
branching
patterns
transcriptionally
Moreover,
in
vivo
physiological
analysis
each
subtype
threshold
range
responses
mechanical
and/or
thermal
stimuli.
findings
support
model
morphologically
physiologically
sensory
tile
stimulus
space
collectively
encode
wide
natural
Abstract
For
decades,
great
strides
have
been
made
in
the
field
of
immunometabolism.
A
plethora
evidence
ranging
from
basic
mechanisms
to
clinical
transformation
has
gradually
embarked
on
immunometabolism
center
stage
innate
and
adaptive
immunomodulation.
Given
this,
we
focus
changes
immunometabolism,
a
converging
series
biochemical
events
that
alters
immune
cell
function,
propose
roles
played
by
diversified
metabolic
derivatives
enzymes,
emphasize
key
metabolism-related
checkpoints
distinct
types,
discuss
ongoing
upcoming
realities
treatment.
It
is
expected
future
research
will
reduce
current
limitations
immunotherapy
provide
positive
hand
responses
exert
broader
therapeutic
role.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Апрель 23, 2023
Summary
Mechanical
and
thermal
stimuli
acting
on
the
skin
are
detected
by
morphologically
physiologically
distinct
sensory
neurons
of
dorsal
root
ganglia
(DRG).
Achieving
a
holistic
view
how
this
diverse
neuronal
population
relays
information
from
to
central
nervous
system
(CNS)
has
been
challenging
with
existing
tools.
Here,
we
used
transcriptomic
datasets
mouse
DRG
guide
development
curation
genetic
toolkit
interrogate
transcriptionally
defined
neuron
subtypes.
Morphological
analysis
revealed
unique
cutaneous
axon
arborization
areas
branching
patterns
each
subtype.
Physiological
showed
that
subtypes
exhibit
thresholds
ranges
responses
mechanical
and/or
stimuli.
The
somatosensory
toolbox
thus
enables
comprehensive
phenotyping
most
principal
Moreover,
our
findings
support
coding
scheme
in
which
activation
tile
multiple
dimensions
stimulus
space.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Апрель 4, 2024
Abstract
The
roles
of
Aβ
low-threshold
mechanoreceptors
(LTMRs)
in
transmitting
mechanical
hyperalgesia
and
alleviating
chronic
pain
have
been
great
interest
but
remain
contentious.
Here
we
utilized
intersectional
genetic
tools,
optogenetics,
high-speed
imaging
to
specifically
examine
functions
Split
Cre
labeled
mouse
Aβ-LTMRs
this
regard.
Genetic
ablation
-
increased
nociception
not
thermosensation
both
acute
inflammatory
conditions,
indicating
a
modality-specific
role
gating
nociception.
Local
optogenetic
activation
-Aβ-LTMRs
triggered
after
tissue
inflammation,
whereas
their
broad
at
the
dorsal
column
still
alleviated
hypersensitivity
inflammation.
Taking
all
data
into
consideration,
propose
model,
which
play
distinctive
local
global
or
pain,
respectively.
Our
model
suggests
strategy
plus
inhibition
for
treating
hyperalgesia.
International Journal of Molecular Sciences,
Год журнала:
2022,
Номер
23(17), С. 9935 - 9935
Опубликована: Сен. 1, 2022
Chronic
itch
is
one
of
the
most
prominent
clinical
characteristics
diverse
systematic
diseases.
It
a
devastating
sensation
in
pathological
Despite
its
importance,
there
are
no
FDA-labelled
drugs
specifically
geared
toward
chronic
itch.
The
associated
complex
pathogenesis
and
causes
escalate
to
being
top
challenges
healthcare.
Humanized
antibodies
against
IL-13,
IL-4,
IL-31
proved
effective
treatment
itch-associated
atopic
dermatitis
but
remain
be
validated
There
still
satisfactory
anti-itch
therapeutics
available
itch-related
neuropeptides
including
GRP,
BNP,
SST,
CGRP,
SP.
newly
identified
potential
targets
OSM,
NMB,
glutamate,
periostin,
Serpin
E1
have
opened
new
avenues
for
therapeutic
development.
Proof-of-principle
studies
been
successfully
performed
on
antagonists
these
proteins
their
receptors
animal
models.
Their
translational
interventions
humans
need
evaluated.
great
importance
summarize
compare
emerging
knowledge
pathways
promote
development
novel
therapeutics.
goal
this
review
analyze
different
physiologies
pathophysiologies
mediators,
whilst
assessing
suitability
as
discussing
future
Itch
is
a
cutaneous
sensation
that
critical
in
driving
scratching
behavior.
The
long-standing
question
of
whether
there
are
specific
neurons
for
itch
modulation
inside
the
brain
remains
unanswered.
Here,
we
report
subpopulation
itch-specific
ventrolateral
orbital
cortex
(VLO)
distinct
from
pain-related
neurons.
Using
Tet-Off
cellular
labeling
system,
showed
local
inhibition
or
activation
these
VLO
significantly
suppressed
enhanced
itch-induced
scratching,
respectively,
whereas
intervention
did
not
affect
pain.
Conversely,
suppression
pain-specific
affected
pain
but
itch.
Moreover,
fiber
photometry
and
immunofluorescence
verified
itch-
their
functional
activity
histological
location.
In
addition,
downstream
targets
were
different.
Together,
present
study
uncovers
an
important
specifically
modulates
processing.
Cell Reports,
Год журнала:
2023,
Номер
42(11), С. 113316 - 113316
Опубликована: Окт. 26, 2023
Pain
and
itch
coding
mechanisms
in
polymodal
sensory
neurons
remain
elusive.
MrgprD+
represent
a
major
population
mediate
both
mechanical
pain
nonhistaminergic
itch.
Here,
we
show
that
chemogenetic
activation
of
elicited
pain-
itch-related
behavior
dose-dependent
manner,
revealing
an
unanticipated
compatibility
between
neurons.
While
VGlut2-dependent
glutamate
release
is
required
for
transmission
from
neurons,
the
neuropeptide
neuromedin
B
(NMB)
selectively
signaling.
Electrophysiological
recordings
further
demonstrated
synergizes
with
NMB
to
excite
NMB-sensitive
postsynaptic
Ablation
these
spinal
abolished
signals
without
affecting
signals,
suggesting
dedicated
itch-processing
central
circuit.
These
findings
reveal
distinct
neurotransmitters
neural
circuit
requirements
signaling
providing
new
insights
on
processing