PAIN

Endorphin & Enkaphalin

Kelompok 6

Pain Pathway

Pain pathway

Different pain states

Acute nociception :
Activation of small high
Examples : hot
threshhold sensory
plates,
needle
afferents, A & C
prick, incisions
Spinothalmic tracts
anterior cingulate
cortex ( limbic system)

Different pain states

Tissue injury
example,: Burns,
abrasion, joint
inflamation,
musculoskeletal
injury

Nerve Injury
Activation of A

Examples : nerve
compression,
chemotherapy,
diabetes

Pain and the Endogenous Opioid

System
Pain is modulated by endogenous opioid
peptides
Opioid Classes

Opioid
Receptor
Types

Endorphins

Mu (Supraspinal)

Enkephalins

Delta (spinal, supraspinal)

Dynorphins

Kappa(spinal)

Endomorphins (?)

Mechanism analgesia
Supraspinal action

Mechanism analgesia
Spinal Opiate Action

Endorphins Endogenous Morphin

Endorphin produced in the brain and
aterior pituitary
Endorphin inhibits pain perception. It
is popularly called Bodys natural
analgesic or opiate

Types of Endorphin
alpha ()
endorphin
beta ()
endorphin
gamma ()
endorphin
Sigma ()
endorphin

Most
powerful
-

-endorphin
-endorphin is peptide hormones
released by pituitary (into blood) and
hypothalamus (into the spinal cor
and brain)
-endorphin is a cleavage product of
pro opiomelanocortin (POMC)

-endorphin

Receptor of endorphin
Mu receptor

Mechanism reseptor of
endorphin

Mechanism reseptor of
endorphin

Mechanism reseptor of endorphin

Can we get endorphin?

Effect by endorphin

Mood alterations

Mood alteration & rewarding

properties

CNS depression Respiration

Direct depression of rhythm
generation in ventolateral medulla
Desensitization of brainstem
chemoreceptors which normally
respond to rising PCO2
Also desensitize the carotid and
aortic chemosensors which usually
respond to hypoxia

Effect on Cough
Direct inhibitory effect on the
coughcentre of medulla
There is no relation between the
supression of cough and respiratory

Other effects
Effect on nausea and emesis
Direct stimulation of CTZ
Miosis :
parasimpathetic pathways by inhibition
of GABAergic tolerance
Motor tone :
high doses increase the muscle tone
chest wall rigidity, increased propensity
to myoclonus

Neuroendocrine Effects
Broadly opioids block the release of
many hormones of the HPA axis
Adrenal and sex steroid hormones
general decrease in the release of
testosteron, DHEA, cortisol and also
the gonadotrophins from the pituitary

Neuroendocrine Effects
Prolactin
Increased secretion due to loss of
inhibitory control of dipamine
Oxytocin and vasopressin
KOR agonists inhibit the release of
both the hormones

Cardiovascular Effects
Peripheral vasodilatation, reduced
peripheral resistance and inhibtion of
baroreceptor reflexes,
histamine release
Coronary artery desease
decreasing preload, inotropy and
chronotropy
decrease in O2 consumption, left
ventricular and diastolic volume and
cardiac work

Cardiovascular Effects
Respiratory depression
retention
cerebral vasodilatation
in ICT
Can be arrhythmogenic

CO2
increase

Effect on GI Tract
Opioid receptors dense distribution in the
enteric plexuses
Stomatch :
- delays gastrict emptying
- also decreases the secretion of HCl
Intestine
- diminishes propulsive activity in both SI & LI
- Intestinal secretions are reduced by
inhibitory effects on secretomotor neurons

Effect on other smooth

muscle
Ureter & Urinary Bladder
- inhibition of urinary voiding reflex
- increase in the tone of external
sphincter
increase the volume of the bladder
Uterus
restores the tone of hyperactive
bladder secondary to oxytocics

Effect on immune system

Opioid receptors are present on
different cells of the immune system
like neutrophils, natural killer cels
direct modulation of their function
Suppression of HPA axis.

Enkephalin
They are 5 amino acids long
Also have met enkephalin (methionine at 5
position) and leu enkephalin (leucine at 5
position)
Enkephalins are neuromodulators since
they are small peptides, it was found that
they came from larger peptides
(proenkephalins)
Cleavage of proenkephalin gives 4 to 5
pieces of activated enkephalins

Reseptor enkephalin
Delta reseptor
Delta agonists show poor analgesia
and little addictive potential
May regulate mu receptor activity

Delta reseptor

Analgesia
Release of growth hormone
Affective behavior
Present in limbic system

Mechanism reseptor of
enkephalin

Mechanism reseptor of
enkephalin

Mechanism reseptor of
enkephalin