Free Nerve Ending (FNE)

00:00 Free Nerve Endings.

00:03 Free nerve endings are important for specially temperature and pain modulation.

00:09 Let’s start off with pain.

00:11 Pain can be enacted by a number of substances and molecules released in the skin.

00:18 Mast cell are one of the most important.

00:20 And mast cells release histamine and prostaglandins.

00:26 These two things will cause a pain response.

00:31 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.

00:43 Besides mast cells, you can traumatize certain areas of skin.

00:47 What do I mean by traumatize it? –Agitate it, you can pinch it, you can rub it too much.

00:53 And that traumatized layers of skin will also produce prostaglandins that can cause pain.

00:59 Other ways that stressed skin releases substances are things like potassium, bradykinin, even hydrogen ions.

01:08 All of those substances can stimulate the free nerve endings to cause a painful response.

01:14 Even sensory afferents can release substance P which gives the perception of pain in that area.

01:22 And finally sometimes even cholinergic agonists.

01:26 These are things that you normally use in the skin to do things like cause sweat glands to sweat.

01:32 If they’re overactive or there is too much acetylcholine in the area.

01:36 That too can stimulate your free nerve ending pain receptor.

01:40 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.

01:52 Now, cutaneous nocireceptor or pain fibers can act in a few ways.

01:57 One is there is a response in which they are polymodal.

02:01 These means they may respond to one or more stimuli.

02:07 And why this is important is because you can have mechanical stimuli that cause nocireceptor responses.

02:15 Chemical reasons to cause nociceptor responses and thermal receptors that can cause nocireceptor responses.

02:23 So let me go through a couple of examples with you.

02:26 So if you have a mechanical issue, that might be something like if you took the skin and it was cut.

02:34 Or maybe a chemical component is you' re releasing local chemicals.

02:39 Or maybe you spilled something like acid on your skin.

02:43 However, sometimes you can have both mechanical and thermal components at the same time.

02:49 And that would be a polymodal type of a response.

02:55 So let’s go through this temperature aspect of causing pain.

03:00 There are nocireceptors for cold and nocireceptors for heat.

03:05 Now these are separate nocireceptors than the ones that cause sensations of cold or sensations of warm.

03:13 So these are separate population of free nerve endings.

03:18 The ones that respond to cold utilize these trip channels.

03:23 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.

03:40 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.

03:48 It can even feel like a burn when it’s get on some places in the skin as well.

03:54 A feeling of cold is a menthol feeling. And that is that feeling of evaporation or that cool.

04:02 That is not painful yet. To get to the painful cold response, you use a TRP 1 a channel.

04:10 This TRP 1 a channels are associated with things like mustard or horse radish.

04:16 That is the sensation one gets when whoa it’s so cold but hurts at the same time.

04:22 So you can see that TRPV1 and TRPA1 are the two things that mediate these noxious cold and noxious heat.

04:33 Itch Itch oddly we do not know a lot about.

04:38 It seem like, we should understand how itch works.

04:41 And we understand about it but really we can classify in broad terms.

04:46 Itch is from free nerve endings.

04:50 These are the same free nerve endings that might cause pain.

04:53 They might cause a change in temperature.

04:55 So we’re not, its hard to know when a lot of receptors can do similar things.

05:00 What we know is there are histamine mediated itch and non-histamine mediated itch.

05:07 These are the two classifications that we derive.

05:10 And we know these because if you infuse histamine in the skin, you get this feeling to want to itch.

05:16 And this is often times, what someone who is even doing things like an allergy test is looking for.

05:22 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.

05:29 There is non-histamine mediated but it doesn’t have the same classification because we don’t understand it as well.

05:38 And we don’t have good medications to fight it.

05:40 'Cause we for example have antihistamine, anti-age creams that we can apply.

05:45 And that takes away the histamine mediated itch but doesn’t touch the non-histamine mediated itch.

05:51 We’ll have to keep investigating that one.