Scientific Reports,
Journal Year:
2019,
Volume and Issue:
9(1)
Published: July 26, 2019
The
infrapatellar
fat
pad
(IFP)
serves
as
a
reservoir
of
Mesenchymal
Stem
Cells
(MSC),
and
with
adjacent
synovium
plays
key
roles
in
joint
disease
including
the
production
Substance
P
(SP)
affecting
local
inflammatory
responses
transmitting
nociceptive
signals.
Here,
we
interrogate
human
IFP-derived
MSC
(IFP-MSC)
reaction
to
pro-fibrotic
environments
(cell
priming
by
TNFα/IFNγ
TNFα/IFNγ/CTGF
exposure
respectively),
compared
bone
marrow-derived
(BM-MSC).
Naïve
IFP-MSC
exhibit
increased
clonogenicity
chondrogenic
potential
BM-MSC.
Primed
cells
experienced
dramatic
phenotypic
changes,
sharp
increase
CD10,
upregulation
immunomodulatory
transcripts,
secreted
growth
factors/cytokines
pathways
(IL-10,
TNF-α,
MAPK,
Ras
PI3K-Akt).
Naïve,
more
so
primed
(both)
induced
SP
degradation
vitro,
reproduced
their
supernatants
abrogated
thiorphan,
CD10
inhibitor.
These
findings
were
vivo
rat
model
acute
synovitis,
where
transiently
engrafted
reduction.
Functionally,
demonstrated
sustained
antagonism
activated
peripheral
blood
mononuclear
(PBMC)
proliferation,
significantly
outperforming
declining
dose-dependent
effect
naïve
cohorts.
Collectively,
our
vitro
data
supports
cell
way
enhance
immunoregulatory
properties
IFP-MSC,
which
selectively
engraft
areas
active
synovitis/IFP
fibrosis
inducing
degradation,
resulting
cell-based
product
alternative
BM-MSC
potentially
treat
degenerative/inflammatory
diseases.
International Journal of Molecular Sciences,
Journal Year:
2019,
Volume and Issue:
20(13), P. 3130 - 3130
Published: June 26, 2019
Chronic
pain
is
a
condition
in
which
progresses
from
an
acute
to
chronic
state
and
persists
beyond
the
healing
process.
impairs
function
decreases
patients’
quality
of
life.
In
recent
years,
efforts
have
been
made
deepen
our
understanding
develop
better
treatments
alleviate
pain.
this
review,
we
summarize
results
previous
studies,
focusing
on
mechanisms
underlying
development
identification
neural
areas
related
We
review
association
between
negative
affective
states.
Further,
describe
structural
functional
changes
brain
structures
that
accompany
chronification
discuss
various
neurotransmitter
families
involved.
Our
aims
provide
guidance
for
future
therapeutic
approaches
could
be
used
management
Bone Research,
Journal Year:
2023,
Volume and Issue:
11(1)
Published: Aug. 4, 2023
Abstract
Low
back
pain
(LBP)
is
the
world’s
leading
cause
of
disability
and
increasing
in
prevalence
more
rapidly
than
any
other
condition.
Intervertebral
disc
(IVD)
degeneration
facet
joint
osteoarthritis
(FJOA)
are
two
common
causes
LBP,
both
occur
frequently
elderly
women
populations.
Moreover,
(OA)
OA
pain,
regardless
joint,
experienced
by
up
to
twice
as
many
men,
this
difference
amplified
during
menopause.
Changes
estrogen
may
be
an
important
contributor
these
states.
Receptors
for
have
been
found
within
IVD
tissue
nearby
joints,
highlighting
potential
roles
surrounding
IVDs
joints.
In
addition,
supplementation
has
shown
effective
at
ameliorating
progression,
indicating
its
use
a
therapeutic
agent
people
with
LBP
pain.
This
review
comprehensively
examines
relationship
between
conditions
summarizing
recent
preclinical
clinical
findings.
The
molecular
mechanisms
which
relieve
associated
FJOA
discussed.
Frontiers in Neuroscience,
Journal Year:
2019,
Volume and Issue:
13
Published: Nov. 20, 2019
Tachykinins
(TKs)
are
ancient
neuropeptides
present
throughout
the
bilaterians
and
are,
with
some
exceptions,
characterized
by
a
conserved
FX1GX2Ramide
carboxy
terminus
among
protostomes
FXGLMamide
in
deuterostomes.
The
best-known
TK
is
vertebrate
substance
P,
which
mammals,
together
other
TKs,
has
been
implicated
health
disease
important
roles
pain,
inflammation,
cancer,
depressive
disorder,
immune
system,
gut
function,
hematopoiesis,
sensory
processing,
hormone
regulation.
invertebrate
TKs
also
known
to
have
multiple
functions
central
nervous
system
intestine
these
investigated
more
detail
fly
Drosophila
arthropods.
Here,
we
review
protostome
deuterostome
organization
evolution
of
precursors,
peptides
their
receptors,
as
well
functions,
appear
be
partly
across
Bilateria.
We
outline
distribution
brains
representative
organisms.
In
Drosophila,
recent
studies
revealed
early
olfactory
neuromodulation
circuits
controlling
locomotion
food
search,
nociception,
aggression,
metabolic
stress,
release.
signaling
regulates
lipid
metabolism
intestine.
crustaceans,
an
neuromodulator
rhythm-generating
motor
stomatogastric
presynaptic
modulator
photoreceptor
cells.
Several
additional
functional
can
inferred
from
various
brain
circuits.
addition,
there
few
interesting
cases
where
injected
into
prey
animals
vasodilators
salivary
glands
or
paralyzing
agents
venom
glands.
cases,
produced
predator
sequences
mimicking
TKs.
Lastly,
TK-signaling
appears
duplicated
Panarthropoda
(comprising
arthropods,
onychophores,
tardigrades)
give
rise
novel
type
peptides,
natalisins,
distinct
receptor.
natalisins
general,
it
that
widely
distributed
act
at
short
range
neuromodulators
cotransmitters.
Molecular Therapy — Methods & Clinical Development,
Journal Year:
2020,
Volume and Issue:
17, P. 771 - 784
Published: April 11, 2020
The
identification
of
the
most
efficient
method
for
whole
central
nervous
system
targeting
that
is
translatable
to
humans
and
safest
route
adeno-associated
virus
(AAV)
administration
a
major
concern
future
applications
in
clinics.
Additionally,
as
many
AAV
serotypes
were
identified
gene
introduction
into
brain
spinal
cord,
another
key
human
gene-therapy
success
determine
serotype.
In
this
study,
we
compared
lumbar
intrathecal
through
catheter
implantation
intracerebroventricular
cynomolgus
macaque.
We
also
evaluated
two
are
currently
used
clinical
trials:
AAV9
AAVrh10.
demonstrated
delivery
using
achieved
consistent
transgene
expression
motor
neurons
cord
neurons/glial
cells
several
regions,
whereas
led
brain.
contrast,
AAVrh10
rare
neuron
targeting.
Finally,
found
efficiently
targets
respiratory
skeletal
muscles
after
injection
cerebrospinal
fluid
(CSF),
which
represents
an
outstanding
new
property
can
be
useful
treatment
diseases
affecting
both
muscle.
Journal of Clinical Medicine,
Journal Year:
2022,
Volume and Issue:
11(9), P. 2609 - 2609
Published: May 6, 2022
Musculoskeletal
pain
is
a
condition
that
characterises
several
diseases
and
represents
constantly
growing
issue
with
enormous
socio-economic
burdens,
highlighting
the
importance
of
developing
treatment
algorithms
appropriate
to
patient’s
needs
effective
management
strategies.
Indeed,
algic
must
be
assessed
treated
independently
underlying
pathological
process
since
it
has
an
extremely
negative
impact
on
emotional
psychic
aspects
individual,
leading
isolation
depression.
A
full
understanding
pathophysiological
mechanisms
involved
in
nociceptive
stimulation
central
sensitization
important
step
improving
approaches
musculoskeletal
pain.
In
this
context,
bidirectional
relationship
between
immune
cells
neurons
nociception
could
represent
key
point
these
mechanisms.
Therefore,
we
provide
updated
overview
magnitude
problem,
terms
prevalence
costs,
summarise
role
most
molecular
players
development
maintenance
Finally,
based
mechanisms,
propose
model,
called
“musculoskeletal
cycle”,
which
useful
tool
counteract
resignation
starting
for
algorithm
patient
International Journal of General Medicine,
Journal Year:
2023,
Volume and Issue:
Volume 16, P. 3247 - 3256
Published: July 1, 2023
Background:
Pain
management
is
a
critical
aspect
of
healthcare,
aimed
at
alleviating
discomfort
and
improving
the
quality
life
for
individuals
experiencing
acute
or
chronic
pain.
Pharmacological
methods
constitute
primary
approach
to
pain
management,
including
diverse
array
drugs
that
work
through
different
mechanisms.
Aim:
Identifying
medications
commonly
employed
in
focusing
on
their
mechanism
actions,
uses,
efficacy
pharmacological
applications.
Methods:
The
methodology
involved
systematic
search
scientific
literature
using
various
databases,
PubMed,
Scopus,
Google
Scholar.
Relevant
articles
published
between
2000
2023
were
screened
inclusion.
selected
studies
encompassed
original
research,
review
articles,
therapeutic
guidelines
randomized
controlled
trials.
Results:
findings
this
suggest
multimodal
combining
analgesics
can
enhance
relief
while
minimizing
adverse
effects.
It
emphasizes
importance
assessing
intensity,
determining
underlying
etiology,
utilizing
evidence-based
optimize
outcomes.
Conclusion:
are
an
essential
component
strategies
achieve
optimal
article
concludes
with
discussion
emerging
trends
future
directions
novel
drug
targets
advances
delivery
systems.
Keywords:
pain,
pharmacology,
neuroscience,
analgesia,
hypersensitivity
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(5), P. 4811 - 4811
Published: March 2, 2023
Mast
cells
(MCs)
are
tissue
that
derived
from
bone
marrow
stem
contribute
to
allergic
reactions,
inflammatory
diseases,
innate
and
adaptive
immunity,
autoimmunity,
mental
disorders.
MCs
located
near
the
meninges
communicate
with
microglia
through
production
of
mediators
such
as
histamine
tryptase,
but
also
secretion
IL-1,
IL-6
TNF,
which
can
create
pathological
effects
in
brain.
Preformed
chemical
inflammation
tumor
necrosis
factor
(TNF)
rapidly
released
granules
MCs,
only
immune
capable
storing
cytokine
although
it
be
produced
later
mRNA.
The
role
nervous
system
diseases
has
been
extensively
studied
reported
scientific
literature;
is
great
clinical
interest.
However,
many
published
articles
concern
studies
on
animals
(mainly
rats
or
mice)
not
humans.
known
interact
neuropeptides
mediate
endothelial
cell
activation,
resulting
central
(CNS)
In
brain,
neurons
causing
neuronal
excitation
release
cytokines
chemokines.
This
article
explores
current
understanding
MC
activation
by
neuropeptide
substance
P
(SP),
corticotropin-releasing
hormone
(CRH),
neurotensin,
pro-inflammatory
cytokines,
suggesting
a
therapeutic
effect
anti-inflammatory
IL-37
IL-38.