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