SEROTONIN AND PAIN

LEARNING OBJECTIVES
At the end of lecture students should be able to know,
Chemistry of serotonin.
Understand the role of serotonin in CNS.
Understand the relationship of serotonin and pain.
Levels of serotonin.
Function of serotonin.
Serotonin toxicity.

INTRODUCTION

Serotonin or 5-hydroxytryptamine (5-HT) is

a monoamine neurotransmitter.

Biochemically derived from tryptophan, serotonin

is primarily found in the gastrointestinal (GI)
tract, platelets, and in the central nervous
system (CNS) of animals including humans.

It is thought to be a contributor to feelings of well-

being and happiness.
Approximately 90% of the human body's total
serotonin is located in the enterochromaffin
cells in the alimentary canal (gut), where it is
used to regulate intestinal movements.
 The remainder is synthesized
in serotonergic neurons of the CNS, where it has
various functions.
These include the regulation of mood, appetite,
and sleep.
Serotonin also has some cognitive functions,
including memory and learning.
Serotonin secreted from the enterochromaffin
cells eventually finds its way out of tissues into
the blood.
There, it is actively taken up by blood platelets,
which store it.

When the platelets bind to a clot, they disgorge

serotonin, where it serves as
a vasoconstrictor and helps to regulate
homeostasis and blood clotting.

EFFECT OF SEROTONIN ON PAIN

Serotonin is a chemical substance that is located in the
brain and a neurotransmitter that has an effect on the
amount of pain that a person can withstand.
Serotonin normally reduces the intensity of pain
signals sent to the brain.
Serotonin level, can have an effect on pain threshold
too.

Because serotonin helps keep pain gates closed, a

lack of it can make you feel more pain
 Serotonin blocks the perception of pain in the
brain.

It is dispatched to the area of the spinal cord

where substance P (neuropeptide) is being
released, helping to counteract it.

Low serotonin levels can cause elevated

substance P levels.
These elevated levels, sometimes three times
greater in patient suffering with fibromyalgia
syndrome (FM).

Its a physical suppressing of the pain signal.

 Serotonin also increases the flexibility of veins,
arteries and capillaries.

The more flexible they are, the less likely they are
to generate pain.

Serotonin has also been found to play an

important key role in sleep regulation.

Both sleep and serotonin have a positive impact

on pain.

Serotonin is linked in some way to sleep.

Regardless of which is accurate, both sleep and

serotonin have a positive impact on pain.
Serotonin levels are also naturally lower in
women as compared to men, possibly making
them more susceptible to developing chronic pain
symptoms.
The beneficial impact of serotonin could possibly
help back pain or pain in the neck or other
extremities, arthritis pain, fibromyalgia pain, or
neuropathic pain (nerve pain).
 Depression, anger, hostility, sleep disturbances
all result in increase pain transmission to the
brain.
Although a number of neurotransmitters,
neuromodulators, and receptors are likely
involved in modulating the ascending and
descending pain pathways, serotonin and nor
epinephrine have been implicated as principal
mediators of endogenous analgesic mechanisms
in the descending pain pathways .
 The imbalance of serotonin and nor epinephrine
in endogenous pain inhibitory pathways may
contribute to persistent pain.
Serotonin blocks the perception of pain in the
brain.
It is dispatched to the area of the spinal cord
where substance P is being released, helping to
counteract it.
This goes beyond mood it's a physical
suppressing of the pain signal.
LOW SEROTONIN LEVELS

During long bouts of stress, your body works

diligently to keep your brain's serotonin levels
high to protect you from burning out.

Serotonin, a chemical that regulates processes

like sleep and body temperature, is also
susceptible to wearing out over time.

This is especially true if your body is burning

through your serotonin levels are high.
Slightly Low Serotonin Levels - As your body
burns through its supply of serotonin and your
serotonin levels gradually drop, you may begin to
feel a bit scatterbrained.

Low serotonin levels, may lead to feel worn out

by small tasks like walking out to your mailbox.
Moderately Low Serotonin Levels - As serotonin
levels continue to decrease, patient may begin to
feel so sleepy that he want to go to sleep at dusk
and wake up at noon.

During this sleep, though, he may wake up a lot

and worry about small things.
 He may not feel quite up to hanging out with his
friends after work.
Patient hungry all the time or have no appetite at
all, and everything family says to him seems to
make him feel angry or hurt.

In addition to all this, if moderately low serotonin

levels, he may have unexplained body
sensations like hot flashes, stomach pains and
headaches.

Overall, he feel sad and insecure, but he can't

always put your finger on the reason why.
Extremely Low Serotonin Levels - As low
serotonin levels begin to decrease out, patient
may feel a shift in his thinking patterns.

He may begin to think on super speed about

thoughts you can't control.

These thoughts may be about horrible scenes

from past or they may be imagined.

In addition to this, he may feel numb to

everything around him.
Extremely low serotonin levels can cause patient
to overreact to small problems.

If serotonin levels are this low, it is likely to have

scary ("evil") fantasies, feel like need to escape
by taking off in car.
 When there is extremely low serotonin levels
body may continue to feel terrible or worsen
temperature fluctuates, stomach hurts, and head
feels like it's about to explode.
Lowest Serotonin Levels - When serotonin levels
drop dangerously low, it is most likely be
suicidal.
It will feel as though the world would be better off
without you, and you consider ways to end your
life.
If those around you begin to wonder if you are
depressed, seek help as soon as you can.
Depression is extremely common but it is very
treatable.

SEROTONIN TOXICITY

Serotonin syndrome is a potentially life-

threatening drug reaction that may occur
following therapeutic drug, overdose or the
recreational use of certain drugs.
Serotonin syndrome is a predictable
consequence of excess serotonergic activity
at central nervous system (CNS) and
peripheral serotonin receptors.
For this reason, some experts strongly prefer the
terms serotonin toxicity because these more
 accurately reflect the fact that it is a form of
poisoning.
It may also be called serotonin sickness,
serotonin poisoning, hyperserotonemia,
or serotonergic syndrome.
The excess serotonin activity produces a
spectrum of specific symptoms
including,cognitive,autonomic,
and somatic effects. The symptoms may range
from barely perceptible to fatal.
Numerous drugs and drug combinations have
been reported to produce serotonin syndrome.
Diagnosis of serotonin syndrome includes
observing the symptoms produced and a
thorough investigation of the patient's history

The syndrome has a characteristic picture but

can be mistaken for other illnesses in some
people, particularly those with neuroleptic
malignant syndrome.
No laboratory tests can currently confirm the
diagnosis.
Treatment consists of discontinuing medications
which may contribute and in moderate to severe
cases administering a serotonin antagonist.
An important treatment includes controlling
agitation with benzodiazepine sedation.

SIGN AND SYMPTOMS

 Symptom onset is usually rapid, often occurring
within minutes.
Serotonin syndrome encompasses a wide range
of clinical findings.
Mild symptoms may only consist of increased
heart rate, shivering, sweating, dilated
pupils, intermittent tremor or twitching, as well
as over responsive reflexes.
Moderate intoxication includes additional
abnormalities such as hyperactive bowel
sounds, high blood pressure and hyperthermia; a
temperature as high as 40 C (104 F) is
common in moderate intoxication.
The overactive reflexes in moderate cases may
be greater in the lower limbs than in the upper
limbs.
Mental status changes include hyper
vigilance and agitation.
Severe symptoms include severe increases in
heart rate and blood pressure that may lead
to shock.
Temperature may rise to above 41.1
C (106.0 F) in life-threatening cases.
Other abnormalities include metabolic
acidosis, seizures, renal failure, and
disseminated intravascular coagulation these
effects usually arise as a consequence of
hyperthermia.