Molecular Brain,
Journal Year:
2023,
Volume and Issue:
16(1)
Published: May 25, 2023
Abstract
Delta-9-tetrahydrocannabinol
(Δ
9
-THC)
is
known
to
produce
systemic
analgesia
that
involves
CB
1
and
2
cannabinoid
receptors.
However,
there
compelling
evidence
Δ
-THC
can
potently
inhibit
Cav3.2T-type
calcium
channels
which
are
highly
expressed
in
dorsal
root
ganglion
neurons
the
horn
of
spinal
cord.
Here,
we
investigated
whether
produced
by
Cav3.2
vis
a
We
show
spinally
delivered
dose-dependent
long-lasting
mechanical
anti-hyperalgesia
neuropathic
mice,
showed
potent
analgesic
effects
models
inflammatory
pain
induced
formalin
or
Complete
Freund’s
Adjuvant
(CFA)
injection
into
hind
paw,
with
latter
showing
no
overt
sex
differences.
The
mediated
reversal
thermal
hyperalgesia
CFA
model
was
abolished
null
but
unaltered
animals.
Hence,
due
an
action
on
T-type
channels,
rather
than
activation
British Journal of Pharmacology,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 19, 2024
Background
and
Purpose
The
chemotherapy
agent
oxaliplatin
can
give
rise
to
oxaliplatin‐induced
peripheral
neuropathy
(OIPN).
Here,
we
investigated
whether
T‐type
calcium
channels
(Ca
v
3)
contribute
OIPN.
Experimental
Approach
We
chronically
treated
mice
with
assessed
pain
responses
changes
in
expression
of
Ca
3.2
channels.
also
tested
the
effects
channel
blockers
on
cold
sensitivity
wild‐type
null
mice.
Key
Results
Oxaliplatin
treatment
led
mechanical
hypersensitivity
male
female
Mechanical
persisted
both
sexes.
Intraperitoneal
or
intrathecal
delivery
pan
inhibitors
attenuated
but
not
Remarkably
occurred
even
without
treatment.
Unexpectedly,
intrathecal,
intraplantar
intraperitoneal
Z944
TTA‐P2
transiently
induced
Acute
knockdown
specific
3
isoforms
revealed
that
depletion
3.1
males
either
females
triggered
hypersensitivity.
Finally,
reducing
by
disrupting
interactions
between
deubiquitinase
USP5
small
organic
molecule
II‐2
reversed
importantly
did
trigger
allodynia.
Conclusion
Implications
Altogether,
our
data
indicate
differentially
regulation
hypersensitivity,
raise
possibility
could
promote
Molecular Brain,
Journal Year:
2023,
Volume and Issue:
16(1)
Published: May 25, 2023
Abstract
Delta-9-tetrahydrocannabinol
(Δ
9
-THC)
is
known
to
produce
systemic
analgesia
that
involves
CB
1
and
2
cannabinoid
receptors.
However,
there
compelling
evidence
Δ
-THC
can
potently
inhibit
Cav3.2T-type
calcium
channels
which
are
highly
expressed
in
dorsal
root
ganglion
neurons
the
horn
of
spinal
cord.
Here,
we
investigated
whether
produced
by
Cav3.2
vis
a
We
show
spinally
delivered
dose-dependent
long-lasting
mechanical
anti-hyperalgesia
neuropathic
mice,
showed
potent
analgesic
effects
models
inflammatory
pain
induced
formalin
or
Complete
Freund’s
Adjuvant
(CFA)
injection
into
hind
paw,
with
latter
showing
no
overt
sex
differences.
The
mediated
reversal
thermal
hyperalgesia
CFA
model
was
abolished
null
but
unaltered
animals.
Hence,
due
an
action
on
T-type
channels,
rather
than
activation