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Welcome to this presentation about the skin as an endocrine organ.

Firstly I'd like to say thank you. It's a pleasure, a privilege and an honour

to be here at this conference that has been put on by the Madrid School of Osteopathy.

I'll start by giving an introduction to the skin as an endocrine organ.

I'll offer my opinion on this great organ and then support my opinion with some data.

One thing that I think is very important is the social phenomenon

we're starting to see in different types of treatments-

and I'd really like to underline the way the skin functions in relation to the body and especially the effect that touch,

contact and manual therapy can have.

The skin, as an organ, has properties that we are yet to discover.

It is a very complicated organ and during the process of evolution,

it has developed different kinds of functions.

Of course we know that it acts as the primary barrier

against the external environment and
against alterations that occur because of

infections, changes in temperature, thermoregulation, water regulation, protein regulation

among many others factors.

So manual treatment will have various effects on the skin,

one of which being that any physical contact we make will change the reorganisation

of the skin. In fact, anything that affects the skin:

the sun, erythema, temperature will change the proteins in the skin such as filaggrins,

which are long, very complicated proteins, among others.

Of course, if the production of proteins changes, the reaction of the fibroblasts will also change,

as will other things that we won't be able to discuss today

but it is worth noting that the change would have significant consequences.

So I'll continue now, analysing the evolutionary time-frame
of some of the different organs.

For example, the area I'm circling here with my cursor is the last phylogenetic line between us and chimpanzees.

This is where encephalisation began in homo sapiens or in the first human that was classified.

Of course there is still a great deal of anthropological information that is unknown in this area but,

with the information we do have, we can say that encephalisation began approximately 2 million years ago.

We have several different theories about encephalisation, some are to do with nutrition,

others are to do with genetic changes,

which are significant but what I want to focus on is that,

through evolution, our brains have been becoming more specialised over the course of 2 million years.

Of course, we bring with us characteristics from other phylogenetic lines, before speciation.

Some of the characteristics of the nervous system in our flower body

can be traced back to reptiles, while other structures

were developed later when we separated and became mammals, such as the midbrain.

So of course we bear characteristics from further back in history

but perhaps our most human characteristics date back 2 million years.

On the other hand, when it comes to the evolution of the skin,

we have characteristics that have been preserved, the majority of which date back,

as I'm showing you here with my cursor, 312 million years.

Looking at these characteristics that come from reptiles, some of them from frogs specifically.

This study, which is a wonderful study,

talks about the evolutionary process from the skin of frogs, or from reptiles,

to the skin that we have today

and it explains what neuroendocrinology has to do with the transduction,

activation and physiology of thyroid hormones,

thyrotropin-releasing hormone, prolactin, cholecystokinin,

insulin-like growth factors, pheromones- the very well known hormones associated

with mating and with falling in love,

as is the case with humans now- and other secretory activities

in the skin which are associated with molecular patterns

that send alarm signals responding to dangers in the world around us and the immunological functions of the skin.

There is a considerable number of dendritic cells,

which process antigen material. The most well known are mastocytes which

participate in the production of histamine and
everyone who uses manual

treatment will know this because when we touch the skin, it can turn red.

Histamine acts as a neurotransmitter but also as a hormone and can be used

in manual treatment to help us to analyse the treatment

we are using, assessing elasticity and other properties of the kin.

This is something we use a lot when practising manual therapy.

So, we share several functions with other mammals-

when mammals split from reptiles,

I'll indicate the section of the slide I'm referring to with my cursor,

and through the process of speciation, we became what we are today,

we continued sharing the functioning of the majority of our hormones.

Some hormones have specialised in other organs, such as cholecystokinin,

which we mentioned previously and which is now secreted

in our duodenum and delivers bile from the gallbladder but in the frog,

it was associated with the skin.

Characteristics of the skin in reptiles have specialised in other organs and other functions in humans.

But what do we share?

Well, the function of the skin as a barrier against pathogens,

against drastic changes in temperature and against psychosocial and emotional factors.

A very significant area of specialisation in the human skin is our response to physical contact- stroking

massage or any other kind of stimulus.

Of course, our immune system has been preserved- the skin has a very specific

immune system- we have the sebaceous gland,

we have mucus and we have a huge number of receptors in the skin,

which help to heal wounds and to restore the skin.

Ok so returning to what we spoke about at the beginning, look at he note that I have written

here at the bottom of the slide about another author- Johanson-

who won book award in science in 1981 for his discovery of the skeleton

that he called Lucy

which was a little over 3 million years old.

This is one of the earliest studies of the human skin.

I mentioned on the previous slide that our brains date back 2 millions years,

since the closest characterisation to what we are today and now

we are seeing that the skin dates back another million years beyond that.

It is a very complicated organ and it is easy to see

how we have evolved from being worms to later developing brains.

Therefore, the composition- the extremely rich neuroendocrine composition of the skin,

is the product of thousands of years, or rather millions of years of evolution.

So simplifying it will be a bit tricky but this gives us an idea of how important it is.

So, as a neuroendocrine system, the functions of the skin are linked with the endocrinology of the epidermis,

which acts as a physical barrier,

it affects the colour or the levels of melanin in the skin and of course

different skin colours will have a different endocrinology,

which could affect for example absorption of vitamin D3.

It is has sensitivity receptors, it participates in metabolic conversion

and that is why I mentioned insulin-like growth factors

but I think it is also worth noting that it is capable of producing transport proteins.

This is amazing because the binding globulins

or binding proteins, are proteins which join together with
maybe sex hormones,

maybe with growth factors, such as insulin-like growth factors and they deactivate them.

They thereby perform a metabolic function,

which is normally performed by the liver but which can also be performed in the skin- they can change.

well the skin is responsible for rich metabolic conversion

and I will expand more on this later- of steroid hormones,

cortisol and elements related to cortisol into different types of cholesterol precursors,

producing a large number of hormones, secreted from adipose tissue,

including sex hormones and stress hormones among others.

Of course, it also has a significant effect on the production of vitamin D.

It can produce thousands and thousands of units of vitamin D

because of the effect of sunlight exposure on melanocyte.

So we can see in this lower section how the membrane affects the whole body

as these effects are systemic - i.e. the skin,

as an endocrine organ, produces vitamin D

and all of the hormones I have just mentioned, producing a change in general sensitivity.

All of these effects I have described are systemic including this integral structure providing, so to speak,

an immune system responsible, for regulation and scarring for the rest of the body.

It also controls thermoregulation

How? By identifying the environment around us but also by identifying

when we make contact with something cold or something hot,

when contact is heavy or light...

we then adapt to the external sensitivity or temperature in order to, what?

To maintain the homeostasis of ourinternal temperature.

It also produces exocrine secretions

and there is a great deal of vascular activity

which depends on the internal blood supply and which can change the deepest patterns of vascularisation.

Of course, it affects immunological and metabolic activity as well.

The box that you can see on the right shows that our bodies
function

according to a complicated system of both epidermal and dermal endocrine units.

What does this mean?

It means that changes in sensitivity, social behaviour and the way

that we feel is measured by the autonomic nervous system.

So, as you can see, we have- well there are many studies

on this subject but these studies are particularly interesting and
relevant for manual treatment,

showing that there are nerve fibres that we are very
familiar

with such as myelinated A-beta and A-delta afferent fibres,

which rapidly relay information regarding the location and physical characteristics

of contact with the skin- where we are being touched.

They are fibres that travel very very quickly to deliver information

regarding these specific characteristics. We also have unmyelinated afferent fibres -

the very well known C-fibres which are slow conducting

and are associated with emotional properties.

This means that C-fibre signals are integrated,

or have a connection or synapse
with the midbrain,

particularly with the amygdala,

giving us properties that we then categorise as being our emotions,

which means we all experience pain in slightly different ways.

This also of course gives us the sensation of itching.

So, recent studies- this one is from 1999,
from around the beginning of the century-

have described the properties of this third class of fibres,

called C-fibres, which encode the pleasurable properties of touch
and these are called C-tactile afferents or CT.

We know that this type of fibre has a strong connection with specific hormones

such as oxytocin and dopamine and they play a critical role

in the physical and cognitive development
of an individual for the rest of their life.

They can affect an individual's perceptions of life and their desire

to do exercises among other things that I will come on to mention.

So we've seen that pleasurable touch reduces stress,

so during any kind of intervention that you
are doing-

for example preoperative rehabilitation- you should use techniques aimed at improving circulation,

thereby stimulating these fibres to improve the patient's predisposition for recovery.

We also have studies that have looked at care homes for the elderly,

and how we can improve their eating habits.

When the person caring for them offers higher levels of physical touch,

for example in homes that offer physiotherapy, manual therapy, mobilisations etc,

this has been found to improve their social behaviour.

So we've seen that the circuits that transmit pain via touch activate the ‘reward system.’

The reward system is comprised of a set of mediating hormones,

which will mediate or compensate for, for example, a cause of stress.

When we need something, when we're presented with a threat to our immune system

or with pain or with a change in our physical homeostasis,
hunger,

thirst or any kind of stress, our bodies will need to resolve that situation.

So we begin with, for example, a cause of stress and the skin itself can then produce adrenalin and catecholamines and it can produce cortisol.

Our bodies are thereby searching for a a solution to the problem.

Certain hormones will need to mobilise, including hormones that transmit pain,

such as glutamate, which supports memory, learning and other functions.

Once we have gained what we need: when the immune system is repaired or when we find food

if we were hungry- whatever initiated the stress process,

we will have undergone a learning process.

The skin often serves as a medium or this kind of learning process-

the first time you are burned by a flame, you remember it and then you begin to associate heat and fire with burning.

So we need these kind of circuits of hormone connections which help us

by creating this learning process and, ultimately, the reward system.

A reward in this context will be the release of "happy" hormones, such as endorphins, GABA,

dopamine and serotonin and the skin is able to produce these hormones in its capacity as an endocrine organ.

This study on the right shows how different forms of contact release different amounts of endogenous opioids-

endorphins, again, serotonin which don't just help to control the pain but also improve the brain's ability to learn as well as improving your mood.

There are even some hormones, which I'll talk about now,

that can induce you to do exercises.

This means that those of us who offer manual therapy, osteopathy, techniques that involve using physical contact,

may find that our patients stick to changes in social behaviour,

exercise and are generally more likely to follow the strategies and advice that we give them,

post treatment than patients who are not treated with manual therapy.

We know that massage, or any kind of physical contact- and the more focused and specific we are,

making the fibres more efficient, the better- improves perception of the different areas of the body,

it improves integrity so that each biomechanical zone can move independently and it can be used to reduce stress,

not only treating the skin condition but releasing endorphins and oxytocin, improving the patient's quality of life,

level of happiness and general outlook on life.

"Touch therapy" can therefore be used to improve pre-frontal connectivity.

This study presents a question- the question is in the study itself-

and I think it's an extremely interesting and important question.

The purple line that we see in this diagram on the right represents pleasure pathways.

This can change our levels of nociception, learning and neurotransmission all via the endocrine system.

It's interesting because this is very much connected with the pre-frontal cortex of the brain

which is responsible for decision making.

It can influence the system of decision making, so that the patient

makes the correct decision to do their exercises and stick to the behavioural changes made following the treatment.

So we know that oxytocin- and this is a very interesting systematic review

which was published last year- it explains how oxytocin
changes and influences our behaviour,

provides a positive reinforcement and if we associate this positive reinforcement with the behaviour we want to carry out,

we will have better control of our emotions.

My point is that we can cause oxytocin to be released,

using physical touch, knowing that it has an analgesic effect and that when we give the patient cognitive instructions to reinforce a behaviour,

the patient will be more likely to carry out the behaviour and follow our advice post treatment.

Micro social behaviours like eye-contact, speech, touch and affection combine to create social synchrony and reciprocity.

This reciprocity from touch that we know exists is also expressed
in endocrine secretions.

What does this mean?

We know that the more specialised the manual treatment - the more physical,

skin-to-skin contact between the therapist and the patient,

the more the patient will trust us.

We see it every day in our clinical practice,

there is a level of social synchrony, right?

This increases the levels of oxytocin in both individuals.

But, it's worth saying- and the study mentions this- that there is a greater density of these T-fibres

areas of skin with more hair growth than there is in the palms of the hands,

which is interesting to note.

So when people ask me, Amaloha do both the therapist and the patient experience the same effects?

No. The patient will be affected to a greater extent, right?

So we know that physical contact with these fibres will have multiple effects on the patient,

including- as we've said- facilitating social behaviours,

improving the communication of relevant social information,

reducing pain, stimulating the production of oxytocin in the skin and even inhibiting pain.

All of this through well applied contact with the skin and, I repeat, it has been shown that physical,

social contact reduces, in many cases...

reduces, in many cases, stress-induced behaviours. What does this mean?

That we have a certain equilibrium in the endocrinology of our skin,

allowing us to release very complicated networks of hormones

but there has to be a decision made.

I'm going to give an example now
that's very didactic but also quite abstract.

We have to make a decision hormonally.

When a neuron is transmitting multiple different impulses,

it has to choose which one it's going to transmit. How does that work?

Well, the neuron, which fires the impulse, is making a choice.

I always say that if the brain decides to generate different emotions- for example fear,

rage, happiness- all at the same time, we'd be schizophrenic.

We prefer to be either sad or happy and for our hormones to match that- transmitting all of the impulses

that we are actually picking up interoceptively and exteroceptively

and it’s the same with the skin.

We know that endocrinologically, the skin is able to produce large amounts of stress hormones,

but we also know that it has to choose whether to induce calm by releasing oxytocin

So this means that, although this property can be lost

because one of the functions of these T-fibres or C-tactile afferents is to communicate

pleasure as a response to physical touch.

Of course, they inhibit pain but when the pain is pathological,

their ability to produce oxytocin is lost.

That's what I've written in this box at the bottom of the slide.

And what is the impact of that?

When someone has a condition like fibromyalgia, chronic pain, chronic fatigue syndrome,

mitochondrial disorders or any condition like that,
the fibres lose all of the functions

that are described in this box at the top that I'm pointing at- inducing spontaneous action,

social participation and enabling cognitive, social and pain rehabilitation.

Once these functions are lost, we will need to restore the patient's physiology

with stimulation and rehabilitation, applying different manual vascularisation techniques to the skin.

Now, almost all of our techniques we apply to the skin- not the internal techniques

and not the oral techniques although the internal part of the skin,

though lined with mucus, can still act as a mechanical stimulus and it is very parasympathetic,

which means that it regenerates very quickly so this does also apply to oral techniques.

Using these techniques then, we are able to recreate the impulses

fired by these fibres, thereby replicating the activity of the C-fibre.

Good. So, we know that in endocrinology of the skin, elasticity,

hydration, changes in thickness and vascular changes are all heavily influenced by the endocrinological ability of the skin to,

for example, produce oestrogen or oestrogen signalling.

For example, we know that psychosocial or physical stress or stress caused by an infection,

a mechanical problem, surgery- surgery produces significant stress in the skin.

Just imagine, you're going to have a knee operation-

there is nothing more aggressive than that- they cut you open,

they insert the prosthesis or whatever it is they're doing but the skin is broken.

And there is a molecular pattern that expresses damage,

as you can see in this box at the bottom of the slide, we begin to produce substance P,

which is a protein, a neuropeptide, released by stress brought on by inflammation

caused by a surgery for example or by scarring.

This produces a variety of chemical substances: chemokines, cytokines, prostaglandins,

which participate in repairing the skin.

But it also produces significant endocrine activity where the corticotrophin

releasing hormone takes fat from the skin and begins to produce cortisol,

activating the mastocytes, producing histamine and- I haven't got time to go into this now but- then epinephrine and adrenaline.

Adrenaline are produced and this will stimulate the receptors in the body more generally.

So in the moments after surgery,

the skin itself will alter the internal environment of the body,

both through inflammatory responses and neurogenic responses,

changing the patient's behaviour at a systemic level,

affecting their circulation and sending signals to the brain.

So all of these hormones, some that I've mentioned,

others that I haven't from adrenaline,

noradrenaline, cortisol, peptides, the precursors for all of these hormones,

inflammatory substances or inflammatory or anti-inflammatory cascades which signal as hormones,

oestreogen and many many other hormones.

This section refers to what I was saying earlier about growth factors-

these are specific hormones which stimulate growth and repair but which are also closely linked

to resistance to insulin for example with metabolic syndrome or blood sugar disorders.

If the skin loses its capacity to produce transport proteins,

other pathologies may occur as well as there will be nothing in place to stop them.

Transport proteins act as a brake for proliferative activity and proliferative activity

is not something we want because it can bring increased inflammation and increased growth.

This can cause diseases such as endometriosis or cysts or other similar diseases

that occur when this activity isn't inhibited and tissue proliferation occurs.

This can be mediated through changes in the condition of the skin.

So, we know that the skin is an independent endocrine organ,

with the ability to metabolise hormones, to activate hormones and to deactivate hormones.

It isn't just responsible for perception of our external environment, it is a peripheral organ,

the largest organ in the body and able to function independently.

This slide, again, shows all of the different hormones that can be released

and the role that they play in the body as a whole.

The last thing I would like to say is that we shouldn't just talk about the skin as an endocrine organ.

We can perhaps say that the skin is one of the organs with the most endocrine functions and,

although it produces smaller quantities of hormones than other organs,

it does produce the majority of the hormones that we have in our bodies and converts them

into different proteins or fats.

As well as this, the skin has an incredible capacity to-

and this box here shows the CYPs (cytochromes P450 - a superfamily of enzymes)

and each of these either converts one hormone into another, metabolises different types of fat or is responsible for toxicity.

When we improve the physiology of the skin, of the proteins that I mentioned at the beginning,

the physiology around stress, we increase the capacity to experience pleasure,

which in turn improves detoxification both at an immunological level and by converting and eliminating toxic substances.

Ok then, thank you very much. That's the end of my presentation on the skin as an endocrine organ,

I hope to have persuaded you that manual treatment is highly effective and produces positive results on the brain,

behaviour, learning processes, treatment adherence and,
of course, pain management.