DR.%20MANSOOR%20AQIL

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PAIN PATHOPHYSIOLOGY MANAGEMENT DR.
MANSOOR AQIL
B.Sc., M.B.B.S.,
F.C.P.S ASSOCIATE PROFESSOR, KING SAUD
UNIVERSITY CONSULTANT KING KHALID UNIVERSITY
HOSPITAL,RIYADH.

• DR. MANSOOR AQIL
• 
  B.Sc., M.B.B.S., F.C.P.S
• ASSOCIATE PROFESSOR, KING SAUD UNIVERSITY
  CONSULTANT KING KHALID UNIVERSITY
  HOSPITAL,RIYADH.

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PAIN
PAIN

• Word pain is derived from Latin word Poena,
  meaning penalty, suffering or punishment

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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)

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CLASSIFICATION OF PAIN
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TYPES OF PAINAccording to duration

• Acute
• Chronic

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TYPES OF PAINAccording to Etiology

• Postoperative
• OR
• Cancer pain

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TYPES OF PAINAccording to Type of the organ
affected

• Toothache
• Earache
• Headache
• Low backache

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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.

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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.

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PHYSIOLOGICAL PROCESSES IN NOCICEPTION

• Transduction
• Transmission
• Modulation
• Perception

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Mechanisms in Nociception
If it were only that simple..
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Nociception
Transduction Conduction Modulation
Perception
Modulation
Noxious stimulus
Ouch Pain
primary sensory neuron central neuron
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TYPES OF ACUTE PAIN

• Somatic
• OR
• Visceral

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SOMATIC PAIN

• Superficial
• OR
• Deep

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SUBTYPES OF VISCERAL PAIN

• Localized visceral pain
• Referred Visceral pain
• True Localized parietal pain
• Referred parietal pain

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TRUE VISCERAL PAIN

• Dull, diffuse and in Midline
• Frequently associated with sympathetic or
  parasympathetic activity
• Nausea
• Vomiting
• Sweating
• Changes in HR and BP.

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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.

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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
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REFERRED PAIN
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• PAIN PATHWAY

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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

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Nociceptive pathways peripheral sensory nerves
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SPINOTHELAMIC TRACT

• Axons of the second order neurons cross the
  midline form spinothalamic tract Thalamus,
  Reticular formation, Nucleus Raphe Magnus and
  Periaquaductal gray matter.
• Medial tract Medial Thalamus
• Lateral tract Ventral
  Posterolateral Nucleus of Thalamus

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THALAMIC NUCLEI
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ALTERNATE PATHWAYS

1. Spinomesencephalic
2. Spinoreticular
3. Spinohypothalamic
4. Spinotelencephalic
5. Spinocervical
6. In the dorsal column

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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.

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PAIN CENTRE
Post Central Gyrus
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CINGULATE GYRUS
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Receptors ---Free nerve endings
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Receptors ---Free nerve endings

• Mechanoreceptors Pinch and Pinprick
• Silent Nociceptors Inflammation
• Polymodal mechanoheat nociceptors
• Excessive pressure, Extremes of Temperature and
  Alogens like Bradykinin, Serotonin, Histamine, H,
  K, Prostaglandins and ATP.

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Types of Peripheral Fibers
Pain Fibers
Ad and C
A. a, b, d, g
B.
C.

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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.

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PHYSIOLOGY OF NOCICEPTION

• Fast pain (First pain)
• Slow pain (Second pain)

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Peripheral Terminal Activation in Acute pain
Phase 1
First pain - sharp, pricking, localising Ad
fibres myelinated (12-30 m/s)

• Second pain - dull, burning, aching, not
  localised, diffuse
• C-fibres umyelinated slow conduction (0.5 - 2 m/s

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• MODULATION

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MODULATION OF PAIN

• Peripheral Modulation
• Central modulation

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PERIPHRAL MODULATION

• Primary Hyperalgesia
• Secondary Hyperalgesia

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PRIMARY HYPERALGESIA

1.    Decrease threshold
2.     Increase in frequency of response
3. Spontaneous discharge

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State of normosensitivity
Low intensity stimulation
High intensity (noxious) stimulation
Innocuous sensation
PAIN
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State of Normosensitivity Response proportional
to stimulus
Response
Noxious stimulus
DRG
Pain neuron
Central nervous system
Peripheral tissue
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MAST CELLS BASOPHILLS PLATELETS
DAMAGED TISSUE
MAST CELLS PLEATELETS
ACTIVATED FACTOR XII
ALOGENS
HISTAMINE
SEROTONIN
BRADY- KIANIN
PRIMARY HYPRALGESIA STIMULATION OF C- FIBERS
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SENSITIZARION(STIMULATION)
RECEPTOR
PC
G-RPOTEIN
PLC
PIP2
DAG
ARACHADONIC ACID
PKC
IP3
LIPOXY- GENASE
COX
RELEASE INTRACELLULAR CALCIUM
PROSTAG- LANDINS
LEUKOTRINES
THROM- BOXANE
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Peripheral Sensitization
Reduced Transduction Threshold
Primary hyperalgesia
Innocuous/Noxious stimulus
Inflammation
primary sensory neuron central neuron
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Peripheral Sensitization
Tissue damage
Macrophage
IL1b, IL6TNFa
Mast cell

Cox-2
PGS
PG
AA
COX-2 Sensitive
VR1
EP/IP
H
Ca2
PKC
PKA
(SNS/SNS2)
Primary sensory neuron peripheral terminal
There are prostanoid and non-prostanoid
sensitizers
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SECONDRY HYPERALGESIA
SECONDRY 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.

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ANTI- DROMIC CONDUCTIONTRIPPLE RESPONSE

• To spinal cord activation
  of nociceptors
• SP SP SP CGRP?
• Histamine, Serotonin, Oedema
• VASODILATION

INJURY
BLOOD VESSEL
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CENTRAL MODULATION

• STIMULATION
• INHIBITION

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CENTRAL SENSITIZARION(STIMULATION)

• Wind up Sensitization
• Receptor Field Expansion
• Hyperexcitabality of flexion reflexes

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CENTRAL SENSITIZARION(STIMULATION)

• Chemical mediators
• sP,
• CGRP,
• VIP, Angiotensin
• Cholecystokinin
• L- Aspartate L- glutamate
• Galanin
• Substance Y

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Wind up phenomenon
C fibre activation will stimulate mild pain
C-Fibre
NORMAL
Mild pain stimulus
Mild pain
C-Fibre
Mild pain stimulus
Severe pain
Increased nociceptor drive leads to central
sensitisation
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Central Sensitization Receptor field expansion
A? fibre mechanoreceptor
Weak synapse
innocuous stimulus
non-painful sensation
Increased synaptic strength
innocuous stimulus
painful sensation
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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
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SENSITIZARION(STIMULATION)
RECEPTOR
PC
G-RPOTEIN
PLC
PIP2
DAG
ARACHADONIC ACID
PKC
IP3
LIPOXY- GENASE
COX
RELEASE INTRACELLULAR CALCIUM
PROSTAG- LANDINS
LEUKOTRINES
THROM- BOXANE
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Central Sensitization - Acute Phase
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NMDA receptors contribute to spinal cord
sensitisation
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NMDA Receptor Antagonists

• Ketamine
• Amantadine
• Dextromethorphan
• Methadone
• Dextropropoxephene

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INHIBITION
CENTRAL SENSITIZATION (INHIBITION)

•     Segmental inhibition (Gate theory)
• Superaspinal Inhibition

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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

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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

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GATE THEORY OF PAIN
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• 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.

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TRANSCUTANEOUS NERVE STIMULATION (TENS)

• Asymmetric biphasic waveform of
• 12-20mA at 50-100Hz via 1000 ohms resistance
  has proved successful for post operative analgesia

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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

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TENS Advantages

• Noninvasive
• Patient controlled
• No side effects
• Non-addictive
• Decreased analgesic needs

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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

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SUPRASPINAL INHIBITION
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Supraspinal /Modulation
GABA Adensosine Opiate Dopamine Nor-Ephinephrine
VGCC
NMDA
Activity
Glutamate
AMPA
Sub P
mGluR
NK1
Afferent Central Terminal
Dorsal Horn Neuron
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Modulation - Inhibitory

• Supraspinal
• Endorphins,
• Enkephalins,
• Dynorphins,
• Norepinephrine (alpha 2),
• GABA,
• Somatostatin (5HT1),
• Neurotensin

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PAIN NEUROTRANSMITTERS
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• PRE EMPTIVE ANALGESIA

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PRE EMPTIVE ANALGESIA

• Administration of local anesthetics/ analgesics
  may reduce the post operative requirement of
  analgesics due to reduction in pain intensity.

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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.

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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

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SYSTEMIC RESPONCES TO ACUTE PAIN
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Cardiovascular effects

•         Tachycardia
•         Hypertension
•         Increased SVR

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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

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GASTROINTESTINAL AND URINARY EFFECTS

• Sympathetic tone
• Motility, ileus and urinary retention
• Secretion of stomach
• Chance of aspiration
• Abdominal distension leads to decreased
  chest excursion

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ENDOCRINE EFFECTS

• Catecholamine, Cartisol and Glucagon
• Insulin and Testosterone
• Increased Aldosterone
• Increased ADH
• Increased Angiotensin

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HEMATOLOGICAL EFFECTS

• Platelet adhesiveness
• Fibrinolysis leading to
• Hypercoagulatability

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IMMUNE EFFECTS

• Leukocytosis
• Lymphopenia
• Reduce T killer cell cytotoxicity
• Depression of Reticuloendothetial system

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GENERAL SENSE OF WELL-BEING

• Anxiety
• Sleep disturbances
• Depression

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PAlN MEASUREMENT

• Descriptive scales such as
• Mild.
• Moderate.
• Severe
• Generally unsatisfactory.

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Numerical scaleVAS (Visual Analogue scale)
0 1 2 3 4 5 6
7 8 9 10

• 0 corresponds to No pain
• 10 designates Worst possible pain.

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Wong Baker faces rating scale
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• Wong Baker faces rating scale

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POSTOPERATIVE PAlN

• OUTPATIENTS
• 1 Oral Analgesics
• Cyclooxygenase Inhibitors
• Opioids
• 2. Infiltration of Local Anesthetic

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POSTOPERATIVE PAlN

• INPATIENTS
• 1. Opioids
• Subcutaneous Intramuscular Injections
• Patient-Controlled Analgesia
• 2. Peripheral Nerve Blocks

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I/M or I/V I N J E C T I O N S
HYPNOSIS
SEDATION
ANALGESIA
PAIN
TIME
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POSTOPERATIVE PAlN

• INPATIENTS
• 3. Central Neuraxial Blockade Intraspinal drugs
• Local Anesthetics
• Opioids
• Local Anesthetic Opioid Mixtures

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HYPNOSIS
SEDATION
DESIRED ANALGESIA
PAIN
TIME
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PCA (patient controlled analgesia)
PCA analgesia has been used successfully in
patients ranging in age from 7-90 years of age.
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PCA (patient controlled analgesia)
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HYPNOSIS
SEDATION
PCA IV, Epidural, Transdermal patch
ANALGESIA
PAIN
TIME
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Anesthesia
HYPNOSIS
SEDATION
Overdose
Naloxone
ANALGESIA
PCA IV, Epidural, spinal Transdermal patch
PAIN
TIME
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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

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• Chronic pain

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PATHOPHYSIOLOGY OF CHRONIC PAIN

• Chronic pain may be caused by a combination of
• Peripheral,
• Central,
• Or psychological mechanisms.
• Sensitization of nociceptors plays a major role

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EVALUATING THE PATIENTWITH PAlN

• Why?

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EVALUATING THE PATIENTWITH PAlN

• Acute pain is primarily therapeutic
• Chronic pain additionally involves investigative
  measures.

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EVALUATING THE PATIENTWITH PAlN

• A written questionnaire
• Nature of the pain,
• Onset
• Duration,
• Previous medication and treatments.
• Diagrams can be useful in defining patterns of
  radiation.

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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.

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• 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

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DIAGNOSTIC THERAPEUTICNEURAL 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

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• 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.

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Cervicothoracic (Stellate) Block
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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.

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PHARMACOLOGICALINTERVENTIONS

• Pharmacological interventions in pain management
  include
• COX inhibitors,
• Opioids,
• Antidepressants,
• Neuroleptic agents,
• Anticonvulsants,
• Corticosteroids,
• Systemic administration of local anesthetics
• Alpha 2 agonists
• Botulinum toxin

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THERAPEUTIC ADJUNCTS

• PSYCHOLOGICAL INTERVENTIONS
• PHYSICAL THERAPY
• Heat and cold
• ACUPUNCTURE

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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)

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Permanent Implantable IPG
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CANCER PAIN

• ORAL OPlOlD THERAPY
• TRANSDERMAL OPlOlDS
• PARENTERAL THERAPY
• INTRASPINAL OPlOlDS
• NEUROLYTIC TECHNIQUES

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Transdermal patchFentanyl 50 mic/hr
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ALCOHOL PHENOLNEUROLYTIC BLOCKS

• Neurolytic blocks are indicated for patients with
  severe intractable cancer pain

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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.

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Radiofrequency Neurotomy
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