Free Nerve Endings.
Free nerve endings are important for
specially temperature and pain modulation.
Let’s start off with pain.
Pain can be enacted by a number of
substances and molecules released in the skin.
Mast cell are one of the most important.
And mast cells release
histamine and prostaglandins.
These two things will cause a pain response.
How did they do it?
These substances can bind to a free nerve ending
and that free nerve ending senses
histamine or prostaglandins as painful.
Besides mast cells, you can
traumatize sort areas of skin.
What I mean by traumatized it, agitated.
You can pinch it. You can rub it too much
and that traumatized layers of skin will also
produce prostaglandins that can cause pain.
Other ways that stressed skin
released substances are things like
potassium, bradykinin, even hydrogen ions.
All of those substances can stimulate the free
nerve endings to cause a free nerve response.
Even sensory afferents can release substance P
which cause the perception of pain in that area.
And finally sometimes even cholinergic agonist.
These are things that you normally
use in the skin to do things like
cause sweat glands to sweat.
If they’re overactive or there is
too much acetylcholine in the area.
That too can stimulate your free
nerve ending pain receptor.
So all of these molecules are felt
or perceived by the body as painful
when they're in the skin and touching or
in close park semi to a free nerve ending.
Now, cutaneous nocireceptor or
pain fibers can act in a few ways.
One is there is a response
in which they are polymodal.
These means they may respond
to one or more or stimuli.
And why this is important is because
you can have mechanical stimuli
that cause nocireceptor responses.
Chemical reasons to cause nociceptor
responses and thermal receptors
that can cause nocireceptor responses.
So let me go through a couple
of example with you.
So if you have a mechanical issue,
that might be something like
if you were took the skin and it was cut.
Or maybe a chemical component is
your releasing local chemicals.
Or maybe you spilled something
like acetone on your skin.
However, sometimes you can have both mechanical
and thermal components at the same time.
And that would be a polymodal type of a response.
So let’s go through this temperature
aspect of causing pain.
There are nocireceptors for
cold and nocireceptors for heat.
Now these are separate nocireceptors than the ones
that cause sensations of
cold or sensations of warm.
So these are separate population
of free nerve endings.
The ones that respond to cold
utilize these trip channels.
And these trip channels are
ones for heat using trip one
which is also known as a capsaicin sensitive
channel because if capsaicin is around,
it will bind to it and you’ll get
that feeling of noxious heat.
What is capsaicin?
It is the same thing that’s in chili oil or hot peppers
feels like it burns when it’s all on the tongue.
It can even feel like a burn when it’s
get on some places in the skin as well.
A feeling of cold is a menthol feeling.
And that is that feeling of evaporation or that cool.
That is not painful yet. To get to the painful
cold response, you use a TRP 1 a channel.
This TRP 1 a channels are associated
with things like mustard or horse radish.
That is the sensation one gets when
whoa it’s so cold but hurts at the same time.
So you can see that TRPV1 and
TRPA1 are the two things that mediate
these noxious cold and noxious heat.
Itch oddly we do not know a lot about.
It seem like, we should understand how itch works.
And we understand about it but
really we can classify in broad terms.
Itch is from free nerve endings.
These are the same free nerve
endings that might cause pain.
They might cause a change in temperature.
So we’re not, its hard to know when
a lot of receptors can do similar things.
What we know is there are histamine
mediated itch and non-histamine mediated itch.
These are the two classifications that we derive.
And we know these because if you infuse histamine in the skin,
you get this feeling to want to itch.
And this is often times, what someone who is even
doing things like an allergy test is looking for.
They’re looking for a little bit of
raise in the skin, a little bit of edema
and that feeling of wanting to itch a certain spot.
There is non-histamine mediated but
it doesn’t have the same classification
because we don’t understand it as well.
And we don’t have good medications to fight it.
'Cause we for example have antihistamine,
anti-age creams that we can apply.
And that takes away the histamine mediated itch
but doesn’t touch the non-histamine mediated itch.
We’ll have to keep investigating that one.