<s>
A	O
nociceptor	B-Algorithm
(	O
"	O
pain	B-Algorithm
receptor	I-Algorithm
"	O
from	O
Latin	O
nocere	O
'	O
to	O
harm	O
or	O
hurt	O
 '	O
)	O
is	O
a	O
sensory	B-Architecture
neuron	I-Architecture
that	O
responds	O
to	O
damaging	O
or	O
potentially	O
damaging	O
stimuli	O
by	O
sending	O
"	O
possible	O
threat	O
"	O
signals	O
to	O
the	O
spinal	O
cord	O
and	O
the	O
brain	O
.	O
</s>
<s>
Nociceptors	B-Algorithm
were	O
discovered	O
by	O
Charles	O
Scott	O
Sherrington	O
in	O
1906	O
.	O
</s>
<s>
The	O
specific	O
receptors	O
for	O
these	O
intense	O
stimuli	O
were	O
called	O
nociceptors	B-Algorithm
.	O
</s>
<s>
In	O
mammals	O
,	O
nociceptors	B-Algorithm
are	O
found	O
in	O
any	O
area	O
of	O
the	O
body	O
that	O
can	O
sense	O
noxious	O
stimuli	O
.	O
</s>
<s>
External	O
nociceptors	B-Algorithm
are	O
found	O
in	O
tissue	O
such	O
as	O
the	O
skin	O
(	O
cutaneous	O
nociceptors	B-Algorithm
)	O
,	O
the	O
corneas	O
,	O
and	O
the	O
mucosa	O
.	O
</s>
<s>
Internal	O
nociceptors	B-Algorithm
are	O
found	O
in	O
a	O
variety	O
of	O
organs	O
,	O
such	O
as	O
the	O
muscles	O
,	O
the	O
joints	O
,	O
the	O
bladder	O
,	O
the	O
visceral	O
organs	O
,	O
and	O
the	O
digestive	O
tract	O
.	O
</s>
<s>
Nociceptors	B-Algorithm
develop	O
from	O
neural-crest	O
stem	O
cells	O
.	O
</s>
<s>
The	O
neural-crest	O
stem	O
cells	O
split	O
from	O
the	O
neural	O
tube	O
as	O
it	O
closes	O
,	O
and	O
nociceptors	B-Algorithm
grow	O
from	O
the	O
dorsal	O
part	O
of	O
this	O
neural-crest	O
tissue	O
.	O
</s>
<s>
All	O
neurons	O
derived	O
from	O
the	O
neural	O
crest	O
,	O
including	O
embryonic	O
nociceptors	B-Algorithm
,	O
express	O
the	O
TrkA	O
,	O
which	O
is	O
a	O
receptor	O
to	O
nerve	O
growth	O
factor	O
(	O
NGF	O
)	O
.	O
</s>
<s>
However	O
,	O
transcription	O
factors	O
that	O
determine	O
the	O
type	O
of	O
nociceptor	B-Algorithm
remain	O
unclear	O
.	O
</s>
<s>
Following	O
sensory	O
neurogenesis	O
,	O
differentiation	O
occurs	O
,	O
and	O
two	O
types	O
of	O
nociceptors	B-Algorithm
are	O
formed	O
.	O
</s>
<s>
They	O
are	O
classified	O
as	O
either	O
peptidergic	O
or	O
nonpeptidergic	O
nociceptors	B-Algorithm
,	O
each	O
of	O
which	O
express	O
a	O
distinct	O
repertoire	O
of	O
ion	O
channels	O
and	O
receptors	O
.	O
</s>
<s>
The	O
nonpeptidergic	O
nociceptors	B-Algorithm
switch	O
off	O
the	O
tropomyosin	O
receptor	O
kinase	O
A	O
or	O
TrkA	O
and	O
begin	O
expressing	O
Ret	O
,	O
which	O
is	O
a	O
transmembrane	O
signaling	O
component	O
that	O
allows	O
the	O
expression	O
of	O
glial	O
cell	O
line-derived	O
neurotrophic	O
factor	O
(	O
GDNF	O
)	O
.	O
</s>
<s>
This	O
transition	O
is	O
assisted	O
by	O
Runx1	O
which	O
is	O
vital	O
in	O
the	O
development	O
of	O
nonpeptidergic	O
nociceptors	B-Algorithm
.	O
</s>
<s>
On	O
the	O
contrary	O
,	O
the	O
peptidergic	O
nociceptors	B-Algorithm
continue	O
to	O
use	O
TrkA	O
,	O
and	O
they	O
express	O
a	O
completely	O
different	O
type	O
of	O
growth	O
factor	O
.	O
</s>
<s>
There	O
currently	O
is	O
a	O
lot	O
of	O
research	O
about	O
the	O
differences	O
between	O
nociceptors	B-Algorithm
.	O
</s>
<s>
The	O
peripheral	O
terminal	O
of	O
the	O
mature	O
nociceptor	B-Algorithm
is	O
where	O
the	O
noxious	O
stimuli	O
are	O
detected	O
and	O
transduced	O
into	O
electrical	O
energy	O
.	O
</s>
<s>
When	O
the	O
electrical	O
energy	O
reaches	O
a	O
threshold	O
value	O
,	O
an	O
action	B-Algorithm
potential	I-Algorithm
is	O
induced	O
and	O
driven	O
towards	O
the	O
central	O
nervous	O
system	O
(	O
CNS	O
)	O
.	O
</s>
<s>
The	O
sensory	O
specificity	O
of	O
nociceptors	B-Algorithm
is	O
established	O
by	O
the	O
high	O
threshold	O
only	O
to	O
particular	O
features	O
of	O
stimuli	O
.	O
</s>
<s>
Only	O
when	O
the	O
high	O
threshold	O
has	O
been	O
reached	O
by	O
either	O
chemical	O
,	O
thermal	O
,	O
or	O
mechanical	O
environments	O
are	O
the	O
nociceptors	B-Algorithm
triggered	O
.	O
</s>
<s>
The	O
majority	O
of	O
nociceptors	B-Algorithm
are	O
classified	O
by	O
which	O
of	O
the	O
environmental	O
modalities	O
they	O
respond	O
to	O
.	O
</s>
<s>
Some	O
nociceptors	B-Algorithm
respond	O
to	O
more	O
than	O
one	O
of	O
these	O
modalities	O
and	O
are	O
consequently	O
designated	O
polymodal	O
.	O
</s>
<s>
Other	O
nociceptors	B-Algorithm
respond	O
to	O
none	O
of	O
these	O
modalities	O
(	O
although	O
they	O
may	O
respond	O
to	O
stimulation	O
under	O
conditions	O
of	O
inflammation	O
)	O
and	O
are	O
referred	O
to	O
as	O
sleeping	O
or	O
silent	O
.	O
</s>
<s>
Nociceptors	B-Algorithm
have	O
two	O
different	O
types	O
of	O
axons	O
.	O
</s>
<s>
They	O
are	O
myelinated	O
and	O
can	O
allow	O
an	O
action	B-Algorithm
potential	I-Algorithm
to	O
travel	O
at	O
a	O
rate	O
of	O
about	O
20	O
meters/second	O
towards	O
the	O
CNS	O
.	O
</s>
<s>
Thermal	O
nociceptors	B-Algorithm
are	O
activated	O
by	O
noxious	O
heat	O
or	O
cold	O
at	O
various	O
temperatures	O
.	O
</s>
<s>
There	O
are	O
specific	O
nociceptor	B-Algorithm
transducers	O
that	O
are	O
responsible	O
for	O
how	O
and	O
if	O
the	O
specific	O
nerve	O
ending	O
responds	O
to	O
the	O
thermal	O
stimulus	O
.	O
</s>
<s>
Mechanical	O
nociceptors	B-Algorithm
respond	O
to	O
excess	O
pressure	O
or	O
mechanical	O
deformation	O
.	O
</s>
<s>
These	O
mechanical	O
nociceptors	B-Algorithm
frequently	O
have	O
polymodal	O
characteristics	O
.	O
</s>
<s>
Chemical	O
nociceptors	B-Algorithm
have	O
TRP	O
channels	O
that	O
respond	O
to	O
a	O
wide	O
variety	O
of	O
spices	O
.	O
</s>
<s>
Apart	O
from	O
these	O
external	O
stimulants	O
,	O
chemical	O
nociceptors	B-Algorithm
have	O
the	O
capacity	O
to	O
detect	O
endogenous	O
ligands	O
,	O
and	O
certain	O
fatty	O
acid	O
amines	O
that	O
arise	O
from	O
changes	O
in	O
internal	O
tissues	O
.	O
</s>
<s>
Like	O
in	O
thermal	O
nociceptors	B-Algorithm
,	O
TRPV1	O
can	O
detect	O
chemicals	O
like	O
capsaicin	O
and	O
spider	O
toxins	O
and	O
acids	O
.	O
</s>
<s>
Although	O
each	O
nociceptor	B-Algorithm
can	O
have	O
a	O
variety	O
of	O
possible	O
threshold	O
levels	O
,	O
some	O
do	O
not	O
respond	O
at	O
all	O
to	O
chemical	O
,	O
thermal	O
or	O
mechanical	O
stimuli	O
unless	O
injury	O
actually	O
has	O
occurred	O
.	O
</s>
<s>
These	O
are	O
typically	O
referred	O
to	O
as	O
silent	O
or	O
sleeping	O
nociceptors	B-Algorithm
since	O
their	O
response	O
comes	O
only	O
on	O
the	O
onset	O
of	O
inflammation	O
to	O
the	O
surrounding	O
tissue	O
.	O
</s>
<s>
Nociceptor	B-Algorithm
neuron	O
sensitivity	O
is	O
modulated	O
by	O
a	O
large	O
variety	O
of	O
mediators	O
in	O
the	O
extracellular	O
space	O
.	O
</s>
<s>
Peripheral	O
sensitization	O
represents	O
a	O
form	O
of	O
functional	O
plasticity	O
of	O
the	O
nociceptor	B-Algorithm
.	O
</s>
<s>
The	O
nociceptor	B-Algorithm
can	O
change	O
from	O
being	O
simply	O
a	O
noxious	O
stimulus	O
detector	O
to	O
a	O
detector	O
of	O
non-noxious	O
stimuli	O
.	O
</s>
<s>
Inflammation	O
is	O
one	O
common	O
cause	O
that	O
results	O
in	O
the	O
sensitization	O
of	O
nociceptors	B-Algorithm
.	O
</s>
<s>
Allodynia	O
can	O
also	O
be	O
caused	O
when	O
a	O
nociceptor	B-Algorithm
is	O
damaged	O
in	O
the	O
peripheral	O
nerves	O
.	O
</s>
<s>
With	O
this	O
situation	O
,	O
surviving	O
dorsal	O
root	O
axons	O
of	O
the	O
nociceptors	B-Algorithm
can	O
make	O
contact	O
with	O
the	O
spinal	O
cord	O
,	O
thus	O
changing	O
the	O
normal	O
input	O
.	O
</s>
<s>
Although	O
these	O
neurons	O
may	O
have	O
different	O
pathways	O
and	O
relationships	O
to	O
the	O
central	O
nervous	O
system	O
than	O
mammalian	O
nociceptors	B-Algorithm
,	O
nociceptive	B-Algorithm
neurons	I-Algorithm
in	O
non-mammals	O
often	O
fire	O
in	O
response	O
to	O
similar	O
stimuli	O
as	O
mammals	O
,	O
such	O
as	O
high	O
temperature	O
(	O
40	O
degrees	O
C	O
or	O
more	O
)	O
,	O
low	O
pH	O
,	O
capsaicin	O
,	O
and	O
tissue	O
damage	O
.	O
</s>
<s>
Due	O
to	O
a	O
historical	O
misunderstanding	O
of	O
pain	O
,	O
nociceptors	B-Algorithm
are	O
also	O
inappropriately	O
referred	O
to	O
as	O
pain	B-Algorithm
receptors	I-Algorithm
.	O
</s>
