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Natural Pain Killers In The Human Body: How
They Are Produced and How They Work (Part 1)

The human body is able to do so many incredible things automatically. For instance,
did you know that a womans breastmilk changes composition to fit the needs of the
baby as he or she grows? Like during the first few days after giving birth, the color of
the breastmilk is yellow, the so-called colostrum, which is packed-full of antibodies to
help the immune system of the newborn cope up. This is why breastmilk is considered
as the best nutrient source for all babies.

Did you also know that the acid in human stomachs are so strong that they can dis-
solve metals? Yes, stomach acids have an acidity of around 1.5 to 3 pH. While the level
is shockingly low, dont worry, as the acids are produced only when needed, like during
digestion. Plus, the gut is resilient to the acid itself due to its thick mucosal lining. It
also helps that the cells lining the stomach help in regenerating the mucosa every few
days.

It doesn't end there, as the human body is capable of

doing more

Our first instinct at the onset of pain is to reach for some medication to ease it. But be-
fore you do so, why not let your body do what it is capable of doing? After all, the hu-
man body also has natural pain killers. These natural pain killers are produced by the
body itself and unlike chemical medications, there are not much side eects. So if you
want to learn more about how your body copes with pain, keep on reading and enjoy
this informational journey.

1. Enkephalins

The first endogenous opioid peptides to have been discovered in the human body are
enkephalins. The first two kinds of enkephalins that were discovered are methionine
enkephalins and leucine enkephalins. The body, specifically the brain, automatically re-
leases these opioid peptides in times of pain or distress, much like the other neuro-
transmitters that we know of.

Enkephalins can be found in both the human brain and other parts of the nervous sys-
tem. Specifically, enkephalins bind to the delta receptors in areas of the brain like the
pontine nucleus, amygdala, olfactory bulbs and deep cortex. These opioid peptides
inhibit pain by binding to either delta opioid receptors or mu opioid receptors, with a
higher anity for the former.

According to the New Scientist Journal, enkephalins are produced by interneurons dur-
ing stimuli-induced situations. After their release, they bind to the specific receptors
and inhibit the production of substance P. Since this neurotransmitter, substance P, is a
mediator of inflammation, blocking it inhibits the pain pathway as well. Additionally,
enkephalins also modulate the firing of interneurons, thereby lessening the transmis-
sion of information from one nerve to the other.

The problem with enkephalins, and other endogenously-produced pain killers, is that
they work for the short-term only. This is perhaps the main reason why they aren't as
potent as other chemically-produced pain killers. Thats why some studies, like this
one, investigate on the eect of drugs that can potentiate the eect of enkephalins. In
the aforementioned study, it was found that with just one or two peptidase inhibitors,
the anti-nociceptive activity of enkephalins were greatly reduced. But with combina-
tions of three peptidase inhibitors, the eect is the opposite.

2. Endorphins

Endorphins are also endogenous opioid peptides and chances are, you might have
heard about them before. They are known as the feel-good peptides, as they naturally
give you that high after a workout or an intense run. There are various kinds of endor-
phins such as alpha endorphin, beta endorphin, gamma endorphin and sigma endor-
phin.

Endorphins can be found in the peripheral and central nervous system. In the brain,
they can be specifically found binding to the mu opioid receptors in the hypothalamus,
amygdala, cerebral cortex and olfactory bulb. They can also be found binding to the
mu opioid receptors in the pituitary gland, typically during stressful situations. They
also bind to delta opioid receptors and kappa receptors although at lower anities.

In the peripheral nervous system, endorphins bind to mu opioid receptors and also in-
hibit the release of substance P. This is the same mechanism of how enkephalins work,
since they are essentially in the same family. On the other hand, in the central nervous
system, endorphins bind to the same receptors but instead, inhibit GABA release. With
the suppression of GABA, dopamine can be produced increasingly and the pleasure
pathway is therefore enhanced.

Most of the opioid medications we known today work by binding to mu opioid recep-
tors and mimic the eects of endorphins. The problem is that many of these medica-
tions down regulate the production of endogenous endorphins in our body. Such med-
ications include fentanyl and diazepam, as highlighted by this study. In another clinical
trial on rats, it was found that chronic use of morphine can further lower the bodys in-
nate ability to produce endorphins.

3. Dynorphins

Yet another type of opioid peptides are the dynorphins. The name was derived from
two words, dynamis, which means power, and orphins, referring to their opioid-like
properties. Dynorphins can be released from either axon or dendritic terminals. Over
the years, various types of this opioid peptide has been isolated such as dynorphin a,
dynorphin b, dynorphin 1-17 and dynorphin 1-18, to name a few.

Dynorphins can usually be found in the brain and spinal cord. They usually bind to
kappa opioid receptors. Specifically, in the brain, these are the areas of the hy-
pothalamus, claustrum, locus coeruleus and peri-aqueductal gray. Aside from the
modulatory eects of dynorphins in the reception of pain, they also have roles in anxi-
ety control, body temperature regulation and even psychotic disorders.

The action of dynorphins on the brain is the same as the previously mentioned pep-
tides. They inhibit the release of GABA, thereby increasing the production of dopamine,
which helps in lowering the pain reception of the individual. The primary eect of
dynorphins are inhibitory, so they do not excite the nervous system, one of the reasons
why they can also work for anxiety or epilepsy patients. The other neurotransmitters
that dynorphins seem to have an eect on are serotonin, glutamate and nor-
epinephrine.

Perhaps the main problem with dynorphins is that they provide for conflicting results
when it comes to their eects. In other studies, like this one, dynorphins were found to
have significant eects on the feeling of stress in an animal clinical trial. In another
study, it was found that the kappa receptors themselves might be activated by opioid-
like drugs and it might be better to use antagonists for these receptors instead.

4. Endomorphins

Endomorphins are also opioid peptides that are produced by the body in times of pain.
They are classified into two types, namely: endomorphin-1 and endomorphin-2. The
name endomorphins signify the eects of these peptides, endo meaning endogenous
and morphins meaning like morphines. According to recent studies, endomorphins are
as eective as morphines but without the adverse side eects such as tolerance and
respiratory depression.

The subtype endomorphin-1 can be found in areas of the upper brain including the nu-
cleus accumbens, amygdala, cortex and hypothalamus. The subtype endomorphin-2
can be found in areas within the lower brainstorm and spinal cord. Endomorphins have
the highest binding anities for the mu opioid receptors. Aside from pain transmission,
these peptides are also involved in other bodily functions such as depression, sedation
and arousal.

The exact way of how endomorphins work to relieve pain in humans is not yet known.
There are many studies highlighting the dierent possible ways of how they work
though. For example, in this study, researchers proved that endomorphins inhibit the
calcium influx in cells, thereby attenuating the pain process. In another study, re-
searchers investigated the levels of endomorphins in patients with arthritis. They found
that theres a direct correlation between levels of endomorphins and inflammation.

The function of endomorphins with regards to pain and inflammation is still not conclu-
sive. This is the main downside with them, since they are still at their infancy when it
comes to researches, as compared to the other previously mentioned endogenous
peptides. However, the potential of endomorphins is quite high, as they can aect not
only the reception of pain but also the inflammation process. Hopefully, more research-
es would be done in the future for this field.

Never underestimate the power of your own body

Its amazing and it really knows how to heal itself. As you can see from the endogenous
pain killers above, we have more than one compound that aids our natural healing.
Science is on its way to enhancing these eects by preventing the breakdown of these
natural pain killers. On the second part of our blog post, we would uncover more of
these natural pain killers that are produced by our body. Yes, theres more, so stay
tuned and dont forget to like our Facebook and Twitter pages for more updates!