Pain sensations

Dr Raghuveer Choudhary
Damaged tissues release proteolytic enzymes, K+
&histamine .Proteolytic enzymes act on globulins in the
interstitial Fluid to release kinins.
e.g bradykinin, K+ and histamine stimulate pain receptors
Pain is a protective sensation.
Pain receptors . Free nerve endings
Three types
1. Mechanical pain Receptors.: stimulated by
mechanical injurious stimuli.
2. Thermal pain Receptors. : discussed before.
3. Chemical pain Receptors.: stimulated by
chemical stimuli.
Chemical stimuli include:
bradykinin (most important) serotonin, histamine
& K+.
Distribution of pain receptors
- More : Skin, periosteum, arteries, joint surfaces, &
tentorium
cerebelli and cranial sinuses.
- Less : deep tissues.
- Absent : liver parenchyma, lung alveoli and brain.
►Nerve fibres: A delta and C fibres.
►Adaptation: Slowly (static-tonic) or nonadaptive
receptors.
 Types of pain
Pain is classified according to the:
(a) Site of pain
1. Cutaneous pain.
2. Deep pain.
3. Visceral pain.
(b) Quality of pain
1. Epicritic i.e sharp pricking pain.
2. Protopathic i.e dull aching pain.
3. Burning pain.
 (1) Cutaneous Pain

• Fast (Immediate, acute • Slow (Chronic, burning, aching

• sharp or pricking) throbbing nauseous)
• Felts within 0.1 sec ond . After one second .
• Short-duration. Prolonged;annoying,intolerable.
• Mechanical &ThermalR. Elicited by All types of R.
• A delta fibres. C fibres
• Ends in cerebral cortex. Ends in non specific thalamic
nuclei & Reticular formation.
• Well localized. Poorly localized .
• Not felt in deep tissues Occurs in skin & deep tissues
• Blocked by hypoxia & pressure Blocked by cocaine.
• Neospinothalamic tract Paleospinthalamic tract
• Neurotransmitter: Neurotransmitter
• Glutamate . Substance P.
 Nociceptive Pathways
• Fast • Slow
• A Delta Fibers • C Fibers
• Glutamate • Substance P
• Neospinothalamic • Paleospinothalamic
• Mechanical, Thermal • Polymodal/Chemical
• Good Localization • Poor Localization
• Sharp, Pricking • Dull, Burning, Aching
• Terminate in VB • Terminate; RF
Complex of Thalamus – Tectal Area of Mesen.
– Periaqueductal Gray
 Nociceptive Pathways
• Spinothalamic - Major
– Neo- Fast (A Delta)
– Paleo- Slow (C Fibers)
• Spinoreticular
• Spinomesencephalic
• Spinocervical (Mostly Tactile)
• Dorsal Columns (Mostly Tactile)
 PAIN

• A-DELTA→ Noxious Stimulation → change in

Membrane Potential → Receptor Potential → A. P.

• C-FIBERS: Damaged Cell → Proteolytic Enzymes

Circulating Gamma Globulins

Bradykinin, Substance P

Stimulation of Nerve Ending

Fast pain is transmitted by A delta fibers (5-15
m/sec.) from skin
(mainly), parietal pleura, peritoneum a &
Synovial membrane.
(1) Somatic (motor) reflexes:- Spinal reflexes.
Flexor withdrawal reflex.
(2) Autonomic reactions:-
Cutaneous pain: Pressor effects (increased heart rate & ABP).
DEEP & visceral pain: Depressor effects (decreased heart rate & ABP).
(3) Emotional reactions:-
-Acute pain: Crying and anxiety.
(4) Hyperalgesia:- mainly due to skin lesion. (increased pain sensibility).
Appreciation of pain
- Fast pain; is appreciated in thalamus and cortex.
- Slow pain; is appreciated mainly in thalamus.

Functions of the cortex in pain appreciation

1. Localization of pain 2. Discrimination of type of pain.
3. Modulation of pain by emotional and behavioral factors.
Arousal reaction to pain signals
The non specific thalamic nuclei (intra-laminar
nuclei) and reticular formation have a strong
arousal effect on the brain which prevents sleep
during pain.
Deep pain C. Fibres
Diffuse, Dull aching and Depressor effects.
Causes: - inflammation, ischaemia or muscle spasm.
- Bone fractures; due to stimulation of periosteal pain
receptors.
Characters of deep pain
1. Dull aching or rhythmic cramps.
2. Diffuse (poorly localized).

Depressor autonomic changes: decreased heart rate,

decreased arterial
blood pressure ,nausea & vomiting.
 DEEP PAIN

• Arises from Periosteum & Ligaments

• Continuous Contraction of Muscles

• Poorly Localized

• Associated with Sweating & Changes in Blood

Pressure
• Often Nauseating

• Transmitted via Antero Lateral System

Ischaemic pain
Type of deep pain felt in muscles when their blood
supply is decreased.
The Patients complains of severe pain in the muscles
upon walking or running due to accumulation of pain
producing substances as lactic acid.
Examples
1. Cardiac muscle: angina pectoris.
2. Skeletal muscle: intermittent claudication.
Visceral pain C Fibres
Most of viscera contain only pain receptors.
Pain from viscera is carried a long; C fibres.
Pain from peritoneum, pleura or pericardium:Adelta.
It differs from cutaneous pain
. Sharp cut in the viscera does not cause pain (why).
. Diffuse stimulation of pain nerve ending ® severe pain.
Causes Of Visceral Pain
1. Ischaemia: increased acidic metabolites, bradykinin &
proteolytic enzymes.
2. Inflammation of peritoneal covering of viscera.
3. Irritation (chemical irritation by HCI in peptic ulcer).
4. Overdistension of a hollow viscus e.g urinary bladder.
5. Spasm of a hollow viscus e.g gut, gall bladder or ureter.
Both 4 & 5: Obliteration of blood vesssels ® Ischaemic
pain.
Characters of visceral pain
1. Dull aching or rhythmic cramps.
2. Diffuse (poorly localized).
3. Depressor autonomic changes: decreased heart rate, decreased
arterial
blood pressure ,nausea & vomiting.
4. Rigidity of the overlying muscles.
Limitation of the spread of infection.
Decrease the mobility of the diseased viscus for relief of pain.
5. Referred to the surface area i.e referred pain.
 VISCERAL PAIN
• Arises from Visceral Organs
• Receptors
– Free Nerve Endings of A Delta & C Fibers
– Sparsely Distributed
• Stimulus: Spasm, Distension, Ischemia, Chemical
• Ischemia
– Release Acid Metabolites
– Tissue Degeneration Products Produce Bradykinin &
Proteolytic Enzymes
• Chemicals
– Release of Proteolytic Acid Gastric Juice
 VISCERAL PAIN

• Input to CNS via Autonomic Nerves

• Cell Bodies of Ist Order Neuron

– DRG & Homologous Cranial Nerve Ganglia of VII,
IX , X & Trigeminal Nerve

• Afferent also Enters via Sympathetic Ganglia for

Reflex Control of Visceral Functions
 VISCERAL PAIN
• In CNS Fibers Follow Same Route as that of Other
Pain Fibers
– Poorly Localized, Unpleasant
– Associated with Autonomic Changes & Nausea
– Usually Referred to Superficial Parts of Body

• REFERRED PAIN
– Visceral Pain Usually Referred
– Deep Pain May Also be Referred
Referred pain
Definition
Pain originating from viscera but felt in somatic
structures which supplied by
the same spinal dorsal root ( the same dermatome)
of the diseased viscus.
 Referred pain

• Examples
• 1. Cardiac pain: is felt in left shoulder.
• 2. Gall bladder pain: is felt in tip of right shoulder.
• 3. Appendicular pain: is felt around the umbilicus.
• 4. Gastric pain: is felt between the umbilicus & xiphoid
process.
• 5. Renal pain: is felt in the back, inguinal region &
testicles.
• 6. Teeth pain: referred to other teeth.
 REFERRED PAIN
• Superficial Pain Never Referred
• Visceral Pain - Local & Referred
– May also Radiate to Distant Site
– Cardiac Pain
• Inner Aspect of Left Arm, Right Arm, even to Neck &
Abdomen
– Distension of Ureter
• Pain in Testicles
– Irritation of Parietal Plura & Peritoneum
• Pain Referred to Overlying Surface of Body
– Of Diaphragm
• Tip of Shoulder
 REFERRED PAIN
• Mechanism
– Dermatome Rule
• Parts Develop from Same Embryonic Segment or
Dermatome
• Diaphragm Migrate from Neck
• Heart & Arm have Same Segmental Origin
• Convergence
– Somatic and Visceral Pain Afferents Converge on
Same Second Order Neuron
– Brain Unable to Differentiate Site of Origin
• Hence Pain Felt at Somatic Sites
Mechanism of referred pain
a. Convergence – projection theory
Afferent pain fibres from the skin and viscous
converge on the same cells of SGR or thalamus
and will finally activate the same cortical
neurons. Whatever the source of pain, the
cortex will project it to the skin being
the commenst source of pain.
b. Facilitation theory
Afferents of diseased viscera, give
facilitation to cutaneous
pain cells in Substantia Gelatinosa of
Rolandi (SGR),
Which leads to facilitation of their
stimulation.
 REFERRED PAIN

• Facilitation Effect:

– ↑ Activity in Visceral Pain Afferents Collaterals

Fibers → EPSP in Spinal Neurons Receiving Somatic

Inputs → ↑ Activity in Somatic Neurons →

Continuous Pain
 PAIN
• Intensity of Pain is Proportional to Degree of Tissue
Damage
• Ischemic Pain → Lactic Acid → Nerve Ending
Stimulation
• Muscle Spasm Mechanoreceptor Stimulation
Ischemia
• Transmission of Pain
– A – Delta Fibers: 6 to 30 M/Sec
– C – Fibers: 0.5 to 2 M/Sec
 PAIN
• Mixed Spinal Nerve

• Dorsal Root Ganglia Dorsal Root Dorsal Horn

• A – Delta Fibers
– Terminate in Lamina I of Dorsal Horn Gray Matter (Fast
Pain)Give Local Collateral Branch for Spinal Reflexes
• Second Order Neuron
– Cross to Opposite Side
– Form Anterior Spino-Thalamic Tract (Neospinothalamic Tract)
• Joins Medial Laminiscus → Few Collaterals to R.F.
 PAIN
• Second Order Neuron Thalamus

Post Central Gyrus

• Localization is Good
• Neurotransmitter is Glutamate
• Few Fibers Ascends in Dorsal Column
• Slow pain: C –Fibers Ist Order Neuron

Lamina II and III

 PAIN

• Substantia Gelatinosa of Rolando

• Interneuron Lamina V Second Order

Neuron Cross → Lateral Spinothalamic Tract
• (Paliospinothalamic Tract → Brain Stem Joins →
Medial Leminiscus → Thalamus → Cortex
 Pain
• Brain Stem: Collaterals Given to:
– Reticular Formation at All Levels of Brain Stem
– Hypothalamus
– Peri Ventricular Gray Matter
– Peri Aqueduct Gray Matter
– Most Fibers End in Intralaminar and Reticular Nuclei
of Thalamus
– Non Specific Thalamo Cortical Projections to All Part
of Cerebral Cortex
– To Somato Sensory Cortex SI and SII
 PAIN

• While Entering Spinal Cord

– Fibers Ascends or Descends Few Segments → Enters
Spinal Cord

• Through Many Inter-Neurons

– Information Relayed to Anterior Horn Cells of Same &
Opposite Side for Local & Segmental Reflexes of Spinal
Cord
 PAIN
• Pain & Other Crude Sensations
– Perceived Even in Absence of Cerebral Cortex
• Cortex is Concerned With
– Discriminative, Exact & Meaningful Interpretation of Pain
– Emotional Components of Pain
• Post Injury Pain
– Irritation of Nerve Endings
• Allodynia
– Minor Touch Causes Pain
• Neuropathic Pain
– Occur at Sites Even after Healing of Injury
– Often Resistant to Analgesics
 PAIN
• Mechanism
– Release of Sensitizing Substance
– ↑ Transmission at Synaptic Junctions
– At Finer Level
• ↑ Activity of Pre-Synaptic NMDA Receptors of Primary
Nerve Ending → ↑ Release of Substance P
– Gene Switch
• Sub Population of A-Beta Fibers from Mechanoreceptors
Inputs Start Producing Substance P
• NMDA(N-methyl-D-aspartate)
– Ion Channels Allow Entry of Ca++
 Pain Control Mechanisms
• Peripheral • Central
• Gating Theory • Direct Electrical + to
– Involves Inhibitory brain → Analgesia
Inter-Neuron in Cord • Nociceptive control
impacting
Pathways Descend to
Nociceptive
Projection Neurons
Cord
• Inhibited by C Fibers • Endogenous Opioids
• Stimulated by A
Alpha & Beta Fibers
• TENS
 Pain Modulation
• Examples
– Stress Analgesia

– War Situation When Person Emotionally Charged

– Pain Relieved by
• Acupressure & Acupuncture and Electrical Vibrator

• Gate Control Mechanism

– Proposed by Malzek & Wall
Pain Control Systems
(I) Analgesic system
a) The neurons of the periaqueductal gray area are stimulated by
B endorphin reaching them from hypothalamus (neurons of
periventricular area) or pituitary (through blood).
b) Fibres of periaqueductal and interneurones of sp.cd. Secrete
(Enkephalin)
c) Fibres of raphe magnus nucleus secrete (Serotonin)
d) Inhibitory interneurones in spinal cord secrete (Enkephalin).
 PAIN

• DESCENDING PAIN INHIBITING SYSTEM:

• Fibers Arise from: Peri-Aqueductal Gray matter
Peri-Ventricular Gray Matter
Hypothalamus
Medial Forebrain Bundle
Neurons around IIIrd & IV ventricle
Encephalins
Nucleus Reticularis in Medulla
Spinal Cord Nucleus Raphe
Magnus
 PAIN

• Nucleus Raphe Magnus

Serotonergic
Neurons

• Dorsal Horn of Spinal Cord in Substantia Gelatinosa

• Pre-Synaptic and Direct Inhibition by Blocking Ca ++
Channels
• Blocking of Pain Signals
(II) Brain Opiate System

Opiate receptors in the brain cause pre and postsynaptic

inhibition of the nociceptive pathway.

Sites of opiate receptors

1. Periaqueductal gray area
2. Periventricular aea.
3. Raphe magnus nucleus in medulla.
4. Substantia nigra.
 Opioid peptides
(1) Enkephalins.
Act as neurotransmitters at the analgesic system.
(2) Endorphins
-In hypothalamus act as neurotransmitters.
-In pituitary act as hormone.
Release during stress leading to stress analgesia.
(3) Dynorphin
Very potent analgesic.

Types of opiate receptors

Delta, Mu, Kappa, Sigma & Epislon.
 BRAIN OPIOID SYSTEM
• Opium
– Alkaloid
– Morphine Derived from Opium → Analgesia
– Receptors are Opioid Receptors
• Found in Many Areas of Brain
– Limbic System Hypothalamus, Peri-Ventricular Areas, Pituitary &
Spinal Cord

• Endogenous Substances which Mimic Action of

Opium → Opioid Peptides
– Brain’s Own Morphine
– Act like Neurotransmitter on Opioid Receptors
 BRAIN OPIOID SYSTEM
• Opioid Peptides
– Beta Endorphins
• Derived from Pro-opiomelanocortin
– Met-and Leu-Encephalins
• Derived from-Proencephalins
– Dynorphin
– Derived from Prodynorphin
• Opioid Peptides Cause Pre-synaptic Inhibition
– At Spinal Cord to Block Pain
• Inhibit Release of Substance P
 BRAIN OPIOID SYSTEM
• Cause Post Synaptic Inhibition
– Produce IPSP
• In Limbic Areas & Hypothalamus
– Pain Modulation
• Act Peripherally at Site of Injury
• Opioid Mediated Endogenous Analgesia System →
Activated by Administration of Exogenous Morphine
• Descending Analgesia System
– Under Tonic Inhibitory Control of Mid Brain & Medulla
– Opiates Inhibit these Inhibitory Inter-Neurons
(III) Gate theory
1) Spinal gate:

SGR (substantia gelatinosa of Rolandi) in layers II & III acts as gate. At

this level, there is a group of inhibitory enkephalinergic interneurons
which form the "Pain Inhibitory complex, PIC". When stimulated,
these interneurons block the transmission of pain
sensation by presynaptic inhibition of pain-conducting fibers.
This gate can be closed by:
Impulses from
1. A beta fibres: (rubbing of skin inhibits pain).
2. A delta fibres; counter irritant and acupuncture inhibit
pain. They stimulate cutaneous receptors which send
impulses through A delta fibres stimulate the PIC.
3. Cortico-fugal fibres: (thinking decrease pain).
All these fibers causes presynaptic inhibition of pain by
activating an interneurone which secrete (GABA).
2)Thalamic gate:
The same "gating" mechanism for pain is found also at the
thalamus where
pain signals could be blocked by corticofugal fibers or
facilitated by
intralaminar thalamic nuclei. In this way,
the thalamus considered as a secondary gate far pain
transmission.
Stress analgesia; During stress, Pain is blocked at
two levels :

A) At the thalamus: (the second gate of pain transmission ).

Corticofugal fibers to the thalamus block by presynaptic inhibition the
transmission of pain signals in the thalamus before they reach the cerebral cortex.

B) At the dorsal horn of the spinal cord: (the first gate of pain
transmission).
The hypothalamus, and other parts of the central analgesia system, activate the
spinal PIC which blocks the transmission of pain signals at the dorsal horn.
Melzack and Wall (1965, 1988) developed a comprehensive
theory of pain (‘gate-control theory’) which has generally
received wide support

• Fast ‘touch’ fibres and slow ‘pain’ fibres

connect with substantia gelatinosa (SG) and transmission cells (T
cells) in spinal cord
• T cells send pain information to the brain
• SG acts as “gate” to allow or inhibit T cells
 GATE CONTROL MECHANISM

Type II Fibers
Spino
Thalamic (-) (+)
Pathway (-)

S.G.Cells
T- Cells

(-) A-DELTA &

(+) (-)
C Fibers
Activity in fast fibers tends to close the gate (touch but
no pain) and slow fibers open the gate (pain)

A light touch accompanying a noxious stimulus partially closes

gate (reduces pain) — rub skin to alleviate pain

Psychological factors? Modify gate via descending pathway

and/or release of endogenous opiates (e.g. endorphins) in the CNS
producing analgesic effects.
Ignore pain to escape from greater danger (e.g. death!)
 Headache
• Brain is insensitive to pain.
• Pain sensitive intracranial structure;
• (Arteries, Veins, Nerves and Dura at the base of
the brain)
• Headache is referred pain
• a. Supratenterial is referred along the ophthalmic
n ® frontal Head ache.
• b. Infratentorial is referred along Cervical 2 ®
occipital Headache.
Causes of intracranial headache: 5%
1. Meningeal irritation; me nin gitis ; gen eral ize d.
Br ain tum our; loca lize d.
2. Migraine headache; Abn orma l va scul ar phe nom eno n.
3. Hypertension: He ada che a pu lse Pre ssur e.
4. Low CSF pressure: Rem oval of 20 ml of CS F.
® bra in desc ent ® tra ctio n of th e d ura & h ead ache .
5. Alcoholic headache
al coh ol pr odu ces dir ect meni nge al irrita tio n.
6. Constipation.
Ab sorp tion of tox ins pro duce s di rect me nin geal irri tati on.
 Causes of intracranial headache: 5%

• 1. Meningeal irritation; meningitis ; generalized.

• Brain tumour; localized.
• 2. Migraine headache; Abnorma l vascular phenomenon.
• 3. Hypertension: Headache a pulse Pressure.
• 4. Low CSF pressure: Removal of 20 ml of CSF.
• ® brain descent ® traction of the dura & headache .
• 5. Alcoholic headache
• alcohol produces direct meningeal irritation.
• 6. Constipation.
• Absorption of toxins produces direct meningeal irri tation.
 Causes of extra-cranial headache
95%
• 1. Muscular spasm of scalp and neck
muscles due to emotions .
• 2. Irritation of the nasal sinuses.
• 3. Errors of refraction .
• 4. Otitis media.
• 5. Toothache.
 Hyperalgia(increased pain
sensation)
• 1. primary hyperalgesia;
• It occurs in the inflammed skin due to
decreased threshold of pain receptors
• by bradykinin, K, Histamine and
prostaglandins.
• So non painful stimuli become painful.
 Hyperalgia
Secondary hyperalgesia;
It occurs in normal skin due to increased
threshold of pain receptors. So pain receptors
need stronger stimulus, but once pain is elicited ,it is very
severe
It can be explained by (Convergence facilitation theory).
Impulses from the injured area facilitate a central neuron.
Impulses from the area of
secondary hyperalgesia converge on same central neuron.
The convergence on a central
facilitated neuron explains the exaggerated pain sensibility.
Why the threshold of pain is increased in the area of secondary
hyperalgesia.
The facilitator neuron which arises from the area of primary
hyperalgesia exerts lateral inhibition on the stimulator neuron
which arises from the area of secondary hyperalgesia.