Transcript 5- Pain_Management.ppt

PAIN
PATHOPHYSIOLOGY
&
MANAGEMENT
DR. MANSOOR AQIL
DR. MANSOOR
AQIL
B.Sc., M.B.B.S.,
F.C.P.S
B.Sc., M.B.B.S., F.C.P.S
ASSOCIATE PROFESSOR,
KING SAUD
&&
ASSOCIATE PROFESSOR,
KING UNIVERSITY
SAUD UNIVERSITY
CONSULTANT
KING
KHALID UNIVERSITY
UNIVERSITY HOSPITAL,
CONSULTANT
KING
KHALID
HOSPITAL,
RIYADH.
RIYADH.
PAIN
PAIN

Word pain is derived from
Latin word “Poena”,
meaning penalty, suffering or
punishment
PAIN

An unpleasant sensory and emotional
experience associated with actual or
potential tissue damage or described in
terms of such damage.
(International association of study of pain)
CLASSIFICATION OF PAIN
PAIN
ACUTE
SOMATIC
SUPERFICIAL
CHRONIC
VISCERAL
DEEP
TRUE VISCERAL
DE AFFERENTATION SYMPATHETICALLY
PAIN
MEDIATED PAIN
TRUE PARIETAL REFERED VISCERAL REFERED PARIETAL
TYPES OF PAIN
According to duration
 Acute
 Chronic
TYPES OF PAIN
According to Etiology
 Postoperative
OR
 Cancer pain
TYPES OF PAIN
According to Type of the organ affected
 Toothache
 Earache
 Headache
 Low
backache
TYPES OF PAIN
(According to Pathophysiology)

Nociceptive;
Due to activation or sensitization of peripheral
nociceptors.

Neuropathic:
Due to injury or acquired abnormalities of
peripheral or CNS.
ACUTE PAIN

Caused by noxious stimulation due to
injury, a disease process or abnormal
function of muscle or viscera

It is nearly always nociceptive
Nociceptive pain serves to detect, localize and limit the
tissue damage.

PHYSIOLOGICAL PROCESSES
IN NOCICEPTION

Transduction
 Transmission
 Modulation
 Perception
Mechanisms in Nociception
400 years ago Reneé Descartes described pain transmission:
The flame that burns the hand is transmitted along the nervous
system to the brain as a stimulus, where it torments man as a
small flame
Ouch!
1 Noxious stimulus
2 Activate nociceptors
3 Transmit to Brain
4 Perception of Pain
If it were only that simple…..
Nociception
Transduction
Conduction
Modulation
Perception
Modulation
Noxious
stimulus
“Ouch” Pain
primary sensory neuron
central neuron
TYPES OF ACUTE PAIN
 Somatic
OR
 Visceral
SOMATIC PAIN
 Superficial
OR
 Deep
SUBTYPES OF
VISCERAL PAIN

Localized visceral pain

Referred Visceral pain

True Localized parietal pain

Referred parietal pain
TRUE VISCERAL PAIN

Dull, diffuse and in Midline

Frequently associated with sympathetic or
parasympathetic activity
–
–
–
–
Nausea
Vomiting
Sweating
Changes in HR and BP.
PARIETAL PAIN
 Sharp
(stabbing sensation) either
localized or referred to a distant site.

Phenomenon of visceral pain or parietal pain
referred to cutaneous area results from
embryologic development and migration.
PATTERNS OF REFERRED PAIN
Lungs
T2 – T6
Heart
T1 –T4
Aorta
T1 –L2
Esophagus
T3 – T8
Pancreas & Spleen
T5 –T10
Stomach, liver and gall bladder
T6 –T9
Adrenals
T6 – L1
Small intestine
T6 – T9
Colon
T10 – L1
Ureters
T10 – T12
Uterus
T11 – T12
Bladder and prostate
S2 – S4
Urethra & Rectum
S2 – S4
Kidneys, Ovaries & Testis
T10 – L1
REFERRED PAIN
PAIN PATHWAY
FIRST ORDER NEURON
Reach the spinal cord through dorsal spinal root.
– Some through ventral root
–
–
–
–
Trigeminal N
Gasserian ganglion
Facial N
Geniculate ganglia
Glossopharyngeal N
Superior and Petrosal ganglia
Vagus
Ganglion Nodosum and Jugular ganglia
Nociceptive pathways:
peripheral sensory nerves
Dorsal horn of
spinal cord
Spinothalamic
tract
Nociceptive
Dorsal Root
Ganglion
Peripheral
nerve
Sympathetic ganglion
Viscera
Blood vessels
Skeletal
muscle
Tendon
bundle
Muscle and skin Nociceptive
terminals
receptors
C and Ad
fibres
sensory fibres are
C-fibres and Ad
fibres
C-fibres
umyelinated
Ad myelinated
Slow conduction
velocity
Signal variety of
noxious stimuli polymodal
SPINOTHELAMIC TRACT
Axons of the second order neurons cross
the midline form spinothalamic tract
Thalamus, Reticular formation, Nucleus
Raphe Magnus and Periaquaductal gray
matter.
1. Medial tract
Medial Thalamus
2. Lateral tract:
Ventral
Posterolateral Nucleus of Thalamus
THALAMIC NUCLEI
ALTERNATE PATHWAYS
1.
2.
3.
4.
5.
6.
Spinomesencephalic
Spinoreticular
Spinohypothalamic
Spinotelencephalic
Spinocervical
In the dorsal column
THIRD ORDER NEURON
Located in Thalamus.
Send projections to sensory area 1 &II and
Superior wall of Sylvian fissure.
Interlaminar and medial nuclei
Anterior
Cingulate Gyrus.
PAIN CENTRE
Post Central Gyrus
CINGULATE GYRUS
Receptors ---Free nerve endings
Receptors ---Free nerve endings

Mechanoreceptors: Pinch and Pinprick

Silent Nociceptors:

Polymodal mechanoheat nociceptors:
Inflammation
Excessive pressure, Extremes of Temperature and Alogens like
Bradykinin, Serotonin, Histamine, H, K, Prostaglandins and ATP.
Types of Peripheral Fibers
Pain Fibers Ad and C
A. a, b, d, & g
B.
C.
Classification & Function of
Peripheral Nerve Fibers
A. Myelinated A- Fibers:
 a: Motor , Proprioception (afferent)
 b: Motor, Touch (afferent)
 g: Muscle spindles (efferent)
 d: Pain, Temperature (afferent)
B. Myelinated B-Fibers:
 Pre-ganglionic Sympathetic Fibers
C. Non-Myelinated C- Fibers: Pain, Temperature.
PHYSIOLOGY OF
NOCICEPTION
 Fast
pain (First pain)
 Slow
pain (Second pain)
Peripheral Terminal Activation in
Acute pain: Phase 1
Pain Intensity
First pain - sharp,
pricking, localising
Ad fibres myelinated (1230 m/s)
Second pain - dull, burning,
aching, not localised, diffuse
C-fibres umyelinated slow
conduction (0.5 - 2 m/s
Time
MODULATION
MODULATION OF PAIN

Peripheral Modulation

Central modulation
PERIPHRAL MODULATION

Primary Hyperalgesia

Secondary Hyperalgesia
PRIMARY
HYPERALGESIA
1.
2.
3.
Decrease threshold
Increase in frequency of response
Spontaneous discharge
State of normosensitivity
Low intensity stimulation
Innocuous sensation
High intensity (noxious)
stimulation
PAIN
State of Normosensitivity
Response proportional to stimulus
Response
Noxious
stimulus
DRG
Pain neuron
Peripheral tissue
Central nervous
system
DAMAGED
TISSUE
MAST CELLS
BASOPHILLS
PLATELETS
HISTAMINE
ALOGENS
MAST CELLS
PLEATELETS
ACTIVATED
FACTOR XII
SEROTONIN
BRADYKIANIN
PRIMARY HYPRALGESIA
STIMULATION OF C- FIBERS
SENSITIZARION
(STIMULATION)
RECEPTOR
PC
G-RPOTEIN
PLC
ARACHADONIC
ACID
COX
THROMBOXANE
PIP2
DAG
IP3
PKC
LIPOXYGENASE
PROSTAGLANDINS
LEUKOTRINES
RELEASE
INTRACELLULAR
CALCIUM
Peripheral Sensitization
Reduced Transduction Threshold
Primary hyperalgesia
Innocuous/Noxious
stimulus
Inflammation
primary sensory neuron
central neuron
Peripheral Sensitization
Macrophage
Mast
cell
PGS
VR1
Tissue
damage
Cox-2
AA
PG
EP/IP
H+
IL1b, IL6
TNFa
Ca2+
COX-2
Sensitive
PKC
PKA
(SNS/SNS2)
Primary sensory neuron
peripheral terminal
There are prostanoid and non-prostanoid sensitizers
SECONDRY
SECONDRY
HYPERALGESIA
HYPERALGESIA
“Triple response”
(Neurogenic Inflammation)
 sP and CGRP from collateral axons.

sP degranulates Histamine and 5HT,
vasodilates causing tissue edema and
induces formation of Leukotrines.
ANTI- DROMIC CONDUCTION
“TRIPPLE RESPONSE”
To spinal cord
activation of nociceptors
SP
SP SP CGRP?
BLOOD VESSEL
Histamine, Serotonin, Oedema
VASODILATION
INJURY
CENTRAL MODULATION
 STIMULATION
 INHIBITION
CENTRAL SENSITIZARION
(STIMULATION)

Wind up & Sensitization

Receptor Field Expansion

Hyperexcitabality of flexion reflexes
CENTRAL SENSITIZARION
(STIMULATION)
Chemical mediators:







sP,
CGRP,
VIP, Angiotensin
Cholecystokinin
L- Aspartate & L- glutamate
Galanin
Substance Y
Wind up phenomenon
C fibre activation will stimulate mild pain
NORMAL
C-Fibre
Mild pain
stimulus
Mild pain
C-Fibre
Mild pain
stimulus
Increased nociceptor drive leads to central sensitisation
Severe
pain
Central Sensitization
Receptor field expansion
Ab fibre mechanoreceptor
innocuous
stimulus
innocuous
stimulus
Weak
synapse
Increased
synaptic
strength
non-painful
sensation
painful
sensation
Receptor field expansion
ACQUISITION BY A- FIBRES OF C-FIBRE-PHENOTYPE
A beta fibre
Substance P, BDNF
innocuous
stimulus
Central sensitisation
nociceptor
noxious
stimulus
Post-inflammation & after nerve damage, (2) Phenotype switch, (3)
NGF dependent (4) NK1 & NMDA receptors involved (5) GABA
inhibition (6) induction sensitive to MO
SENSITIZARION
(STIMULATION)
RECEPTOR
PC
G-RPOTEIN
PLC
ARACHADONIC
ACID
COX
THROMBOXANE
PIP2
DAG
IP3
PKC
LIPOXYGENASE
PROSTAGLANDINS
LEUKOTRINES
RELEASE
INTRACELLULAR
CALCIUM
Central Sensitization - Acute Phase
src
NMDA
Activity
Glutamate
Tyr
S/T
pERK
PKC
AMPA
S/T
mGluR
Ca2+
PKA
Sub P
Central Terminal
NK1
IP3
NMDA receptors contribute to spinal
cord sensitisation
EAA receptors:
Na+
AMPA
Na+
Glut
mGluR
NMDA
Glut
Na+
Ca2+
+
Mg2+
Brief
Depolarisation
iCa2+
Sustained
Depolarisation
EXCITATION
EXCITATION
PKC, NOS
NMDA Receptor Antagonists





Ketamine
Amantadine
Dextromethorphan
Methadone
Dextropropoxephene
INHIBITION
CENTRAL SENSITIZATION
(INHIBITION)

Segmental inhibition (Gate theory)

Superaspinal Inhibition
GATE CONTROL OF PAIN

Stimulation of Ab fibers
segmental
inhibition of small primary pain afferents
and reduce response to painful stimuli in
dorsal horn secondary afferents
MECHANISM OF ACTION


Exact mechanisms of actions are as yet unknown and certainly
unproven
1965- Melzack and Wall proposed the Gate Theory of Pain
– Nociceptive A delta/C fibres project in SC to second-order
projection neuron but also send fibres to inhibit an
inhibitory interneuron
– Large myelinated A alpha neurons in DC send collaterals to
activate these same interneurons thereby inhibiting (closing
the gate) the pain sensory action potentials
GATE THEORY OF PAIN

Glycine and GABA are inhibitory transmitters.

GABA A and GABAB
Muscimol and Beclofen.



GABAB increases K conductance
GABAA increases Cl conductance
Glycine also increases Cl conductance
Strychnine and Tetanus toxide are Glycine receptor antagonists
Glycine is facilitatory on NMDA receptors

Adenosine has two types of receptors A1 and A2

A1 inhibits adenyl cyclase and A2 stimulates adenylcyclase.
A1 mediate antinociceptive action.




TRANSCUTANEOUS
NERVE STIMULATION (TENS)

Asymmetric biphasic waveform of
12-20mA at 50-100Hz via 1000 ohms
resistance has proved successful for post
operative analgesia
TRANSCUTANEOUS ELECTRICAL
NERVE STIMULATION (Tens)

Effective

Over all analgesic effect is modest

Absolutely safe for the fetus

Usually causes electrical interference with fetal heart rate when used
concurrently with internal fetal scalp electrode
TENS Advantages
 Noninvasive
 Patient
controlled
 No side effects
 Non-addictive
 Decreased analgesic needs
SUPRASPINAL INHIBITION
Originate from



Cerebral cortex
Thalamus
Reticular formation of brain stem (Ventro-median
Medulla VMM).
 Neurotransmitter is Serotonin.
 NMR & Locus Ceruleu

Nor Adrenaline containing fibers from
SUPRASPINAL INHIBITION
Supraspinal /Modulation
GABA
VGCC
Adensosine
Opiate
Dopamine
Nor-Ephinephrine
Glutamate
Activity
Sub P
NMDA
AMPA
mGluR
NK1
Afferent Central
Terminal
Dorsal Horn
Neuron
Modulation - Inhibitory
Supraspinal
– Endorphins,
– Enkephalins,
– Dynorphins,
– Norepinephrine (alpha 2),
– GABA,
– Somatostatin (5HT1),
– Neurotensin
-
PAIN
NEUROTRANSMITTERS
NEUROTRANSMITTER
RECEPTOR
EFFECT ON NOCICEPTION
Substance P
NK-1
Excitatory
CGRP
Excitatory
Glutamate
NMDA, AMPA,
Kinate, quisqualate
Excitatory
Aspartate
NMDA, AMPA,
Kinate, quisqualate
Excitatory
ATP
P1, P2
Excitatory
Somatostatin
inhibitory
Acetylcholine
Muscarinic
Inhibitory
Enkephalins
,,d
Inhibitory
b -Endorphin
,,d
Inhibitory
Norepinephrine
a
Inhibitory
Adenosine
A1
Inhibitory
Serotonin
5-HT, (5HT3)
Inhibitory
-Aminobutyric Acid
GABA
A, B
Inhibitory
Glycine
Inhibitory
PRE EMPTIVE ANALGESIA
PRE EMPTIVE ANALGESIA

“Administration of local anesthetics/
analgesics may reduce the post operative
requirement of analgesics due to reduction
in pain intensity.”
PRE EMPTIVE ANALGESIA

Pain after surgery is possibly amplified by
noxious events induced by surgical incision
(sensitization).

Idea by Crile and later on by Wall.
PRE EMPTIVE ANALGESIA
Promising results from
experimental studies
•
• Prospective studies in humans show conflicting results
• No ultimate understanding of the nature of pre-emptive
measures needed
SYSTEMIC RESPONCES TO
ACUTE PAIN
Cardiovascular effects



Tachycardia
Hypertension
Increased SVR
RESPIRATORY SYSTEM





O2 demand and consumption
M .V
Splinting and Guarding and decreased
chest excursion
Atelactasis, increased shunting,
hypoxemia
V.C, retention of secretions and chest
infection
GASTROINTESTINAL AND
URINARY EFFECTS




Sympathetic tone
Motility, ileus and urinary retention
Secretion of stomach
Chance of aspiration
Abdominal distension leads to decreased
chest excursion
ENDOCRINE EFFECTS





Catecholamine, Cartisol and Glucagon
Insulin and Testosterone
Increased Aldosterone
Increased ADH
Increased Angiotensin
HEMATOLOGICAL EFFECTS

•
Platelet adhesiveness
Fibrinolysis leading to
Hypercoagulatability
IMMUNE EFFECTS
Leukocytosis
Lymphopenia
Reduce T killer cell cytotoxicity
Depression of Reticuloendothetial system
GENERAL SENSE OF
WELL-BEING

Anxiety
 Sleep disturbances
 Depression
PAlN MEASUREMENT

Descriptive scales such as
– Mild.
– Moderate.
– Severe
Generally
unsatisfactory.
Numerical scale
VAS (Visual Analogue scale)
0
1
2
3
0 corresponds to
10 designates
4
5
6
7
8
9
10
No pain
Worst possible pain.
Wong Baker faces rating scale
Wong Baker faces rating scale
POSTOPERATIVE PAlN
OUTPATIENTS
1 : Oral Analgesics


Cyclooxygenase Inhibitors
Opioids
2. Infiltration of Local Anesthetic
POSTOPERATIVE PAlN
INPATIENTS
1. Opioids

Subcutaneous & Intramuscular Injections

Patient-Controlled Analgesia
2. Peripheral Nerve Blocks
HYPNOSIS
I/M
or
I/V
SEDATION
I
N
J
E
C
T
I
O
N
S
ANALGESIA
PAIN
TIME
POSTOPERATIVE PAlN
INPATIENTS
3. Central Neuraxial Blockade & Intraspinal drugs

Local Anesthetics

Opioids

Local Anesthetic & Opioid Mixtures
HYPNOSIS
SEDATION
DESIRED ANALGESIA
PAIN
TIME
PCA
(patient controlled analgesia)
PCA analgesia has been used successfully
in patients ranging in age from 7-90 years
of age.
PCA
(patient controlled analgesia)
HYPNOSIS
SEDATION
PCA IV, Epidural, Transdermal patch
ANALGESIA
PAIN
TIME
Anesthesia
HYPNOSIS
SEDATION
Overdose
Naloxone
PCA IV, Epidural, spinal
Transdermal patch
ANALGESIA
PAIN
TIME
Potential Benefits of Epidural Analgesia

Superior “dynamic” pain relief (while coughing, deep breathing and
ambulating)

Decreased pulmonary complications

Decreased cardiovascular complications

Attenuated neuroendocrine/metabolic response to surgical stress

Lower incidence of DVT and vascular graft occlusion

Earlier return of bowel function

Decreased time on ventilator

Shorter postoperative stay in ICU

Decreased length of hospitalization

Decreased cost of health care
Chronic pain
PATHOPHYSIOLOGY OF CHRONIC PAIN

Chronic pain may be caused by a
combination of
1. Peripheral,
2. Central,
3. Or psychological mechanisms.

Sensitization of nociceptors plays a major
role
EVALUATING THE PATIENT
WITH PAlN
Why?
EVALUATING THE PATIENT
WITH PAlN

Acute pain is primarily therapeutic

Chronic pain additionally involves
investigative measures.
EVALUATING THE PATIENT
WITH PAlN
A written questionnaire
– Nature of the pain,
– Onset
– Duration,
– Previous medication and treatments.
Diagrams can be useful in defining patterns of radiation.
Investigations

Plain radiographs,
 Computed tomography (CT),
 Magnetic resonance imaging (MRI),
 Bone scans.

MRI is particularly useful for soft tissue analysis
and can show nerve compression.

ELECTROMYOGRAPHY & NERVE
CONDUCTION STUDIES

For confirming the diagnosis of entrapment
syndromes, radicular syndromes, neural
trauma, and polyneuropathies

Can often distinguish between neurogenic
and myogenic disorders
DIAGNOSTIC & THERAPEUTIC
NEURAL BLOCKADE

Can be useful in delineating pain mechanisms,
but, more importantly, it plays a major role in the
management of patients with acute or chronic
pain.

SOMATIC BLOCKS
–
–
–
–
Trigeminal Nerve Blocks
Facial Nerve Block
Glossopharyngeal Block
Cervical Paravertebral Nerve Block

SYMPATHETIC BLOCKS
– Cervicothoracic (Stellate) Block
 A. INDICATIONS  This block is often used in patients with head, neck,
arm, and upper chest pain.
– Intravenous Regional
 Sympathetic Blockade
 A Bier block utilizing guanethidine
 (20-40 mg) can selectively interrupt sympathetic
innervation to an extremity.
Cervicothoracic (Stellate)
Block
DIFFERENTIAL NEURAL BLOCKADE

Pharmacological or anatomic differential neural
blockade has been advocated as a method of
distinguishing somatic, sympathetic, and
psychogenic pain mechanisms.
 The pharmacological approach relies on the
differential sensitivity of nerve fibers to local
anesthetics
 Preganglionic sympathetic (B) fibers are reported to
be most sensitive, closely followed by pain
somatosensory C and A delta fibers and finally motor
fibers (Aa).
 By using different concentrations of local anesthetic,
it may be possible to selectively block certain types
of fibers while preserving the function of others.
PHARMACOLOGICAL
INTERVENTIONS
Pharmacological interventions in pain management
include
–
–
–
–
–
–
–
–
–
COX inhibitors,
Opioids,
Antidepressants,
Neuroleptic agents,
Anticonvulsants,
Corticosteroids,
Systemic administration of local anesthetics
Alpha 2 agonists
Botulinum toxin
THERAPEUTIC ADJUNCTS
PSYCHOLOGICAL INTERVENTIONS
PHYSICAL THERAPY
Heat and cold
ACUPUNCTURE
THERAPEUTIC ADJUNCTS
ELECTRICAL STIMULATION
– Transcutaneous Stimulation
– Spinal Cord Stimulation (SCS)
Proposed mechanisms include activation of descending
modulating systems and inhibition of sympathetic
outflow
– lntracerebral Stimulation
Deep brain stimulation may be used for intractable
cancer pain (periaqueductal and periventricular
gray areas for nociceptive pain)
Permanent Implantable IPG
CANCER PAIN

ORAL OPlOlD THERAPY

TRANSDERMAL OPlOlDS

PARENTERAL THERAPY

INTRASPINAL OPlOlDS

NEUROLYTIC TECHNIQUES
Transdermal patch
Fentanyl 50 mic/hr
ALCOHOL & PHENOL
NEUROLYTIC BLOCKS

Neurolytic blocks are indicated for patients
with severe intractable cancer pain
RADIOFREQUENCY ABLATION &
CRYONEUROLYSIS

Percutaneous radio-frequency ablation relies on the
heat produced by current flow from an active
electrode that is incorporated at the tip of a special
needle. The needle is positioned under fluoroscopy.

Electrical stimulation A z (2'Hz for motor responses
and 50 Hz for sensory responses) via the electrode
and impedance measurement prior to ablation also
help confirm correct positioning.
Radiofrequency Neurotomy
Clinic Programmer