‫بسم هللا الرحمن الرحيم‬
‫﴿و ما أوتيتم من العلم إال قليال﴾‬
‫صدق هللا العظيم‬
‫االسراء اية ‪58‬‬
By
Dr. Abdel Aziz M. Hussein
Assist. Prof. of Medical Physiology
Member of American Society of Physiology
• Reaction to pain includes all the following,
except :• a- increased heart rate
• b- depression
• c- withdrawal reflexes
• d- depressed transmission of pain impulses
along sensory pain fibers
• Pain receptors :• a- become more sensitive with prolonged
stimulation
• b- are stimulated by prostaglandins
• c- are more numerous in viscera than other
tissues
• d- include different morphological types
1) Def,
• System which control pain transmission in CNS or
inhibit pain transmission i.e. endogenous analgesia
system
N.B
• The activity of this system differs from one person to
another and from time to time in the same person.
2) Components :
1. Periventricular
hypothalamic area
2. Periaqueductal
area (PAG)
3. Nucleus raphe
magnus (NRM)
3. Nucleus reticularis
paragigantocellularis
(NRPG)
4. Pain Inhibitory
Complex (PIC)
Ascending
pathway
Glutamate
Substance P
Posterior horn of spinal cord
1st order
neuron of pain
Limbic system
RF
Hypothalamus
Cerebral cortex
PAG
NRM
Serotonin
++
Ascending
pathway
Encephalin
++
•Severe stress
•Strong emotions
NRPGC
Noradrenaline
++
Encephalins
Glutamate -Substance P
Posterior horn of spinal cord
1st order
neuron of pain
•Natural peptide substances produced inside the body and
have the ability to bind the opioids receptors (morphine
receptors) and produce analgesia.
Types: are 3 groups;
1. Enkephalins:
• Derived from proenkephalins
• Present in high conc. in brain stem and spinal cord
• Are 2 main types: leu-enkephalin and met enkephalin.
2. Endorphins:
• Derived from pre-opio-melanocortin “POMC”
• Present mainly in anterior pituitary and hypothalamus.
• Most common type is -endorphins.
3. Dynorphins: same sites of encephalins
•Are receptors which respond to opiates and endogenous
opioids
Types: are 4 subtypes;
1. Delta receptors () respond to enkephalins.
2. Kappa receptors (K) respond to dynorphins
3. Mu receptors (µ) respond to endorphins.
4. Sigma receptors () respond to (4-phenyl-1-(4-
phenylbutyl) piperidine) (4-PPBP)
N.B.
• Neurons in PAG and Raphi nuclei contain opioids
receptors which stimulated by exogenous or endogenous
opioids→ pain suppression
Other Mechanisms for Pain Control and inhibition
Stimulation of thick
myelinated N.F (Abeta)
Stimulation of A delta NF.
Rubbing method
Acupuncture
Interneuron
Rubbing of the skin
A beta fibers
Pain C fiber
Painful stimuli
Interneuron
Acupuncture
A delta fibers
Pain C fiber
Painful stimuli
•Acupuncture has been practiced in China for more than
4000 years as a method for pain relief.
Mechanism:
1- Needles in appropriate body regions are thought to excite
certain sensory neural pathways which
feed into
the
brain stem centers (such as the PAG) involved in the pain
control system, with release of endogenous opioid peptides.
2- Simultaneous suppression of pain transmission at the spinal
pain-gate by acupuncture
• The sites of synapses along the pain pathway are considered
as gates through which pain transmission can be;
 Facilitated (if the gate is open) or
 Blocked (if the gate is closed).
Sites:
 The main pain gates are:
1- Spinal gate: at the SGR.
2- Brain stem gate: at the nuclei of reticular formation.
3- Thalamic gate: At neurons of PVLNT & intalaminar thalamic
nuclei.
3
2
1
At spinal gate pain transmission is blocked by;
1. Supraspinal pathways through the pain control system
activating enkephalin-secreting interneuron
2. Spinal inhibition: through;
• Stimulation of A beta (A beta) by skin rubbing
• Stimulation of A delta by acupuncture and counter irritants
3. Cortico-fugal fibers (as during thinking the pain is ).
• This theory provides basis for various methods of pain
relief
1. Massaging a painful area
2. Applying irritable substances to a painful area (counterirritation)
3. Transcutaneous Electrical Nerve Stimulation (TENS)
4. Acupuncture
TENS
• Are examples for cutaneous pain.
• Itching sense is the sense of desire to scratch the skin
usually accompanying the allergic diseases.
• Tickling sense is the sense of something crawling
through the skin leading to itching sense (e.g.) in case
of scabies.
• The receptors of both belong to the free nerve
endings.
• Both senses are transmitted by type C-non-myelinated
nerve fibers along the anterolateral system.
A) 1st order neuron:
• Afferents from face (ophthalmic N. from upper 1/3 of
face, maxillary N. from middle 1/3 of face, mandibular
from lower 1/3 of face) → to trunk of trigeminal N. →
mother cell in Gasserian Ganglia → central branches
divide into 2 branches
1. Ascending branch end in sensory nucleus (carry
touch and proprioception) and mesencephalic
nucleus (proprioception)
2. Descending branch end in spinal nucleus (carry
pain and temperature)
B) 2nd order neuron:
• From both sensory and spinal nuclei → cross to
opposite side and ascend as trigeminal leminiscus
• End in medial part of PVNT
C) 3rd order neuron:
• From PVNT of thalamus → sensory radiations →
primary somatic sensory area
Area 3,1,2
Sensory radiations
PVNMT
Trigeminal
leminiscus
• It carries the cutaneous sensations from the face,
forehead, and anterior part of the scalp, conjunctiva,
cornea and nasal mucosa
• Also, it carries the proprioceptive sensations from the
mandibular ms
Def:
• Pain felt in the head region
• It is an example of referred pain from deep structures
of head
Pain sensitive structures in the head
A) Extracranial structures
1. All structures in the scalp , covering skull including
skin, fasciae, ms, arteries and nerves
2. Eyes
3. Paranasal sinuses
4. Teeth
Pain sensitive structures in the head
B) Intracranial structures
• Brain is insensitive to pain
• Some structures are sensitive to pain e.g.
1. Arteries e.g. middle meninegial arteries
2. Venous sinuses
3. Parts of dura covering skull base
4. Cranial nerves carrying pain V,IX, X
Site of referral of intracranial headache :
A) Frontal headache:
• Due to stimulation of pain receptors above tentorium
(referred by trigeminal nerve)
B) Occipital headache:
• Due to stimulation of pain receptors below tentorium
(referred by 2nd cervical nerve)
Mechanism:
1. Irritation of pain sensitive structures e.g. in case of
meningitis
2. Pressure or traction on pain sensitive structures e.g.
in brain tumors
3. Dilatation of pain sensitive structures e.g. arterial
dilatation and brain tumors
4. Spasm of ms e.g. spasm of neck and head ms
Causes of Extracranial headache:
• Due to stimulation of pain receptors in extracranial
structures by;
1. Spasm of head and neck ms due to emotional tension
(psychogenic headache).
2. Sinusitis: inflammation of nasal sinuses
3. Eye diseases:
a) Glaucoma →increased intraocular pressure
b) Errors of refraction e.g. astigmatism and myopia
4. Oral causes: e.g. teeth caries.
Causes of Intracranial headache:
1. Meningeal irritation e.g. meningitis, trauma,
alcoholics and constipation (absorption of toxins from
rectum which cause meningeal irritation)
2. Brain tumours cause pressure, traction, or dilatation
of intracranial pain sensitive structures.
3. Changes in CSF pressure:
a) ↓ CSF pressure → compensatory dilatation of blood
vessels
Causes of intracranial headache:
3) Changes in CSF pressure:
b) ↑ CSF pressure → pressure and traction on pain
sensitive structures e.g. in hydrocephalus
4) Dilatation of intracranial arteries → pulsation of
arteries and severe headache as in migraine (due to
release of histamine)
• Hypertension also leads to dilatation of cerebral
vessels and headache
THANKS