Dr Sajith Damodaran Pathophysiology of Pain Treatment of Acute
Postoperative Pain University College of Medical Sciences & GTB
Hospital, Delhi
Slide 2
Objectives: Definition of Pain Anatomy and Physiology of pain
perception Adverse effects of untreated postoperative pain
Modalities of treating postoperative pain Special patient
populations
Slide 3
Pain: Definition An unpleasant sensory and emotional experience
associated with actual or potential tissue damage, or described in
terms of such damage. [IASP] Subjective Sensation and emotion
Unpleasant Psychological, in absence of any stimulus or
pathophysiological cause
Slide 4
Pain: Definition Pain is what the patient says hurts [John
Bonica] Affected by the mental and emotional state,
preconditioning, past experiences and memories. Always subjective.
Varies from person to person Pain is the Fifth vital sign
[JCAHCO]
Slide 5
Acute Pain Normal predicted physiological response to an
adverse chemical, thermal or mechanical stimulus. Generally lasts
less than one month Poorly managed pain leads to chronicity
Pathophysiological changes in both PNS & CNS
Slide 6
Hyperalgesia and Allodynia
Slide 7
Anatomy and Physiology of Pain Nociceptive Receptors: Naked
Nerve Endings In all tissues Specific for pain Stimulus not
specific Pain is not produced by overstimulation of other
receptors
Slide 8
Anatomy and Physiology of Pain Nociceptive Pathways: Afferent
Three neuron First order neurons in Dorsal Root Ganglia Second
order neurons in Dorsal horn Third order neurons in Thalamic nuclei
Second order neurons include nociceptive specific and WDR Dual
ascending system Lateral corticospinal Dorsal column medial
leminiscal Descending modulation by cortex thalamus and brain
stem
Slide 9
Slide 10
Anatomy and Physiology of Pain Fast Pain or First Pain: Sharp
or stinging well localised By stimulation of thermo-mechanical
nociceptors Carried by A delta fibres Transmitted by the Lateral
spinothalamic tract Monosynaptic pathway Usually disappears when
stimulus ends
Slide 11
Anatomy and Physiology of Pain Slow Pain or Second Pain
Delayed, Diffuse Stimulation of polymodal nociceptors Carried by C
fibres Transmitted by the dorsalcolumn medial leminiscal tract
Polysynaptic pathway. Collaterals to midbrain, pontine and
medullary RF, PAG, Hypothalamus Engage Descending modulatory system
Involved in the reflex response to pain and emotional and
motivational aspect
Slide 12
Anatomy and Physiology of Pain Small Myelinated A Fibres Carry
Fast pain 2-5 m diameter 12-30 m/s End mainly in lamina I, II &
V of dorsal horn Small unmyelinated C Fibres Carry slow pain
0.4-1.2 m diameter 0.5-2 m/s End in Lamina I & II of dorsal
horn
Slide 13
Anatomy and Physiology of Pain Efferent modulation of pain:
Descending inhibition Cortex, thalamus, brain stem PAG, nucleus
raphe magnus, locus ceruleus Descend in dorsal column to dorsal
horn
Slide 14
Slide 15
Anatomy and Physiology of Pain Gate Control Theory: Explains
the highly variable and non linear relationship between pain and
injury Pain is gated at the Dorsal Horn Involves WDR neuron Excited
by nociceptors and also A fibres Inhibitory interneurons, excited
by A fibres, inhibited by A and C fibres MOA of TENS, Rubifascients
and counterirritants
Slide 16
1.The projection neuron (P) carries both nociceptive
stimulation from small fibers (S) and non-nociceptive simulation
from large fibers (L) on the way to the brain. 2.With no
stimulation, the inhibitory neuron (I) keeps the gate "closed," and
there is no painful sensation. 3.With painful stimulation, the
small fiber (S) blocks the inhibitory neuron (I), "opening" the
gate for the projection neuron (P) to send on the painful stimulus.
4.With the addition of non-painful stimulation, the large fiber (L)
activates the inhibitory neuron (I), partially or completely
closing the gate depending on the strength of the stimulation, and
competes with the painful stimulation for access to the projection
neuron (P).
Slide 17
Anatomy and Physiology of Pain Other Types of Pain: Deep Pain
Poorly localised, nauseating eg: periosteal pain, pain from
ligaments Muscle Pain Due to ischemia P factor. ? Potassium
Relieved by restoration of blood supply
Slide 18
Anatomy and Physiology of Pain Visceral Pain Poorly localised
and dull sparse receptor concentration Usually felt in midline
Associated with nausea and autonomic disturbances Afferents carried
by ANS Spinal pathways are same as for somatic pain Referred to
other areas
Slide 19
Anatomy and Physiology of Pain Referred Pain Dermatomal Rule
Pain from visceral sites referred to the somatic structure that
developed from the same embryonic segment of dermatome Role of
experience: Pain from abdominal structures may be referred to site
of previous surgery Role of convergence Visceral and somatic
sensory input converge on Dorsal Horn. More fibres in the
peripheral nerve than the STT
Slide 20
Anatomy and Physiology of Pain Neuropathic Pain: Direct nerve
damage like entrapment, cutting, traction, compression etc.
Presents with burning, tingling and other unpleasant sensations in
addition to pain Common surgical procedures Limb amputations Breast
surgery Gall bladder surgery Thoracic surgery Inguinal hernia
repair Responds poorly to typical analgesics
Slide 21
Anatomy and Physiology of Pain Pain Processing - 4 Elements
Transduction Noxious mechanical, chemical and thermal stimuli are
converted to action potential Transmission AP conducted through
nervous system Modulation Alteration of neural transmission along
the pain pathway, principally at dorsal horn Perception Final
common pathway. Integration of painful input into somatosensory and
limbic cortex. Usual analgesic approaches target only
perception
Slide 22
Anatomy and Physiology of Pain Modulation: Augmentation:
Sensitisation due to neuronal plasticity (acute pain induced
changes in the CNS) Inhibition: GABA, Glycine by intrinsic neurons
NA, serotonin, Endorphins by descending efferent cortical and
subcortical input
Slide 23
Pain Processing
Slide 24
Anatomy and Physiology of Pain Chemical Mediators of Pain
Processing: Tissue damage and inflammation activate nociceptors
Release of numerous algogenic substances from the activated
macrophages, mast cells, platelets and lymphocytes Direct pain
transduction and facilitation of transduction by increasing the
excitability of nociceptors
Slide 25
Neurochemistry of impulse processing at peripheral nerve
ending
Slide 26
Anatomy and Physiology of Pain Neurotransmitters in Spinal
Cord: Excitatory Amino Acids Aspartate & Glutamate Excitatory
Neuropeptides Substance P, Neurokinin A Inhibitory Amino Acids
GABA, Glycine
Slide 27
Anatomy and Physiology of Pain Pain Receptors in Spinal Cord:
NMDA ( N-methyly-D-Aspartae ): Ca ++ channel dependent AMPA (
alpha-amino-3-hydroxy-5-methylisoxazole-4-propionicacid ): Na +
channel dependent Kainate: Na + channel dependent Metabotropic
Opioid Receptors: Inhibitory Alpha2 Adrenergic Receptors:
Inhibitory
Slide 28
Postoperative Pain Management: Why manage postoperative pain?
Humanitarian consideration Improved quality of care Better patient
satisfaction Lesser morbidity ? Economic benefits due to enhanced
patient well being and early rehabilitation
Slide 29
CardiovasuclarTachycardia, Hypertension, increased cardiac work
RespiratorySplinting, Decreased VC, Atelectatsis, Hypoxia,
Increased risk of pulmonary infection GastrointestinalPostoperative
Ilieus RenalIncreased risk of oliguria and urinary retention
CoagulationIncreased risk of thromboemboli ImmunologicalImpaired
immune function MuscularMusce weakness and fatigue, increased risk
of DVT PsychologicalAnxiety, Fear, Frustration Consequences of
poorly managed postoperative pain
Slide 30
Assessment of pain Background Pain Pain that is persistant May
vary over time Background Pain Pain that is persistant May vary
over time Breakthrough Pain Pain that escalates above a persistant
Background pain Breakthrough Pain Pain that escalates above a
persistant Background pain Transitory and Intermittant Pain that is
episodic in the absence of background pain Transitory and
Intermittant Pain that is episodic in the absence of background
pain
Slide 31
Assessment of pain Simple Pain Scales: Useful for evaluation of
acute pain Visual Analouge Scale Validated for research Simple to
use Sensitive to small changes Not useful in visually impaired,
cognitively impaired and small children Numerical Rating Scale Less
sensitive Requires patient to be able to translate pain severity to
number. Not useful in visually impaired cognitively impaired and
children Verbal Rating Scale Easy to Use Useful in mildly
cognitively impaired Insensitive to small changes in pain
intensity
Slide 32
Assessment of pain
Slide 33
Useful in children
Systemic Medications: Opioids Transdermal Fentanyl Delivery
System (Ionsys) Needle free, patient activated system for
in-hospital use Iontophoresis Low intensity electrical field used
to transport fentanyl across skin into circulation Each double
click delivers 40mcg over 10 min For us in adults > 18 years
Used for 24 hours or 80 doses
Slide 46
Systemic Medications: Opioids Oral Transmucosal Fentanyl
(ACTIQ): To treat breakthrough cancer pain in opioid tolerant
patients To be sucked by placing in between cheek and lower gums
Each unit to be consumed in 15 minutes Supplied in strengths of
200, 400, 600, 800,1200 & 1600mcg
Slide 47
Systemic Medications: Opioids RoutesIM, IV, PO Duration of
Action2-4 hours Side effectsCNS excitation- seizures, myoclonus due
to nor- pethidine toxicity Interaction with MAO inhibitors,
antidepressants Dose100mg IV/IM q 4 hr 300 mg PO q 4 hr Watch
forNausea,vomiting, euphoria, ventillatory depression sedation
Pethidine: Phenylpiperidine derivative and receptor agonist. Also
has Na + channel blocking and Atopinergic action
Slide 48
Systemic Medications: Opioids Tramadol: Moderate affinity
receptor agonist. Acts on spinal modulating pathways Inhibition of
neuronal NA and Serotonin uptake Stimulation of presynaptic
serotonin release Adverse Effects: Nausea & Vomiting
Ondansetron interferes with analgesic effect Non addictive, less
sedation Dose: 3 mg/kg IM/IV/PO for moderate to severe pain
Slide 49
Systemic Medications: Opioids Pentazocin: Agonist-Weak
antagonist Dose 10-30 mg IV/ 50 mg PO for relief of moderate pain
Side Effects: Dysphoria Sedation Tachycardia, Hypertension
(catecholamine release)
Slide 50
Systemic Medications: Opioids Butorphanol: Agonist-Antagonist
Dose: 2-3 mg IM Also available as intranasal spray Side Effects:
Sedation Nausea Tachycardia, hypertension Less dysphoria than other
agonist antagonists Antagonise other opioids if used together
Slide 51
Systemic Medications: Opioids Buprenorphine: Semisynthetic,
Agonist-Antagonist Routes of administration: IV, IM, Neuraxial, SC,
SL, Trasdermal Useful in morphine intolerant patient Ceiling effect
for respiratory depression, but not for analgesia. Antiflammatory
action Useful in intra-articular injections Prolongs duration of
analgesia in peripheral nerve blocks with LA
Systemic Medications: Opioids Methadone: Synthetic broad
spectrum opioid Mu receptor agonist NMDA antagonist Inhibitor of
monoamine transmitters Useful in treatment of neuropathic pain
Orally well absorbed No dose adjustment in renal disease Drug most
commonly used for opioid rotation
Slide 54
Mechanism of Action Inhibition of Cyclo-oxygenase enzymes (type
1 & 2) Reduce concentrations of PGE2 PGE2 Sensitise peripheral
nociceptors to histamine and bradykinin Centally Increase Substance
P and Glutamate Increase sensitivity of second order neurons
Decrease NTs from descending pathway Centally Increase Substance P
and Glutamate Increase sensitivity of second order neurons Decrease
NTs from descending pathway Systemic Medications: NSAIDs
Slide 55
Adverse Effects: Platelet Dysfunction Gastrointestinal
Ulceration Nephrotoxicity Impaired bone healing Hypersensitivity
Benefits: Opioid Sparing Reduced incidence of opioid side effects
Anti-inflammatory effects
Slide 56
Systemic Medications: NSAIDs DrugRoute & Dose
(mg)Precautions Acetaminophen500-1000 4-6 Hr PO Hepatotoxicity
Aspirin500-1000 q4-6 Hr POReyes syndrome Variable half life
Ibuprofen400 mg q 4-6 Hr, PO Naproxen250mg 6-8 Hr, PO
Indomethacin25 mg 8-12 Hr, PO Ketorolac30 mg initialy, followed by
15-30 mg q 6-8 Hr, IV Correct hypovolumia Elderly Diclofenac50 mg 8
Hr, PO Piroxicam20-40 mg q 24 Hr, PO
Systemic Medications: NMDA Antagonists Ketamine: NMDA receptor
antagonism theoretically reduces central sensitisation,
hyperalgesia and opioid tolreance Currently role in postoperative
pain relief is uncertain Insignificant difference in pain
Clinically insignificant opioid sparing Psychomimetic side effects
hallucination, nighmares
Slide 59
Neuraxial Analgesia: Epidural Analgesia Superior to systemic
opioids Efficacy determined by Catheter-incision site congruency
Choice of analgesic drugs LA+Opioid Rates of infusion Duration of
epidural analgesia At least 2-4 days Type of pain assessment
Dynamic Vs Rest
Slide 60
Neuraxial Analgesia: Epidural Analgesia Dermatomal Guide to
placement Of epidural cathetres
Neuraxial Analgesia: Epidural Analgesia Local Anaesthetics Act
on spinal nerve roots, dorsal root ganglion or spinal cord itself.
High incidence of motor block Hypotension Sign \\\ificant failure
rate due to regression and inadequate analgesia Opioids: Site of
action: Lipophilic: systemic Hydrophilic: spinal Cathetre-Site
congruency not essential No motor blockade No hypotension Analgesia
superior to systemic opioids
Slide 63
Neuraxial Analgesia: Epidural Analgesia PropertyLipophilic
OpioidsHydrophilic Opioids Common DrugsFentayl, SufentanylMorphine,
Hydromorphone Onset of analgesiaRapid (5-10 min)Delayed (30-60min)
Duration of analgesiaShorter (2-4 Hrs)Longer (6-24 hrs) CSF
SpreadMinimalExtensive Site of actionSpinal SystemicSpinal Side
EffectsLower nausea and vomiting, pruritus Early respiratory
depression Nausea & vomiting, pruritus Early ( 6 Hr)
respiratory depression Differences between lipophilic and
hydrophilic opioids
Slide 64
Neuraxial Analgesia: Epidural Analgesia Local
Anaesthetic-Opioid Combinations Additive Effect Superior analgesia,
including dynamic pain relief Limits regression of sensory blockade
Decreased LA dose requirement Analgesia superior to IV PCA with
opioids
Slide 65
Neuraxial Analgesia: Epidural Analgesia Adjuvants: Clonidine:
5-20 g/Hr Dose dependent hypotension, bradycardia Epinephrine conc.
Of 2.5 g/ml Ketamine Theoretically useful in attenuating central
sensitisation
Epidural Analgesia: Adverse Effects Hypotension0.7 3 % with
epidural LAs Motor Block2 3 % with epidural LAs More with
cathetre-incision incongruence Resolves within 2 hours of stopping
infusion If persistant, think of Spinal hematoma/abscess, cathetre
migration Nausea & vomiting 20 50 % with single dose neuraxial
opioid 45 80 % with continuous opioid infusion Dose depdndent. Due
to cephalad migration Less with fentanyl than morphine Treated with
Naloxone, Ondansetrone, Droperidol, Metoclopramide,
Dexamethasone
Slide 68
Epidural Analgesia: Adverse Effects Pruritus60% with Opioids;
15-18 % with LAs Due to cephalad migration and activation of
trigeminal nucleus. ?? Itch centre Treated with Naloxone,
Droperidol Respiratory Depression Incidence 0.1 0.9 % with opioids
Equivalent to systemic administration of opioid Early 6 hr Delayed
depression with Morphine. Due to cephalad spread Risk Factors:
Increasing dose, increasing age, concomitant sedatives, prolonged
and extensive surgery, thoracic surgery Treatment: Naloxone 0.5 5
g/kg/hr Urinary RetentionHigher than with systemic opioids 10 30%
with epidural Las Higher with higher infusion rates of LA
Slide 69
Epidural Analgesia Benefits: (LA based epidurals) Better
attenuation of stress response to surgery Earlier return of GI
function without contributing to bowel dehiscence Decreased
postoperative pulmonary complications Decreased incidence of postop
MI with thoracic epidural Better postop analgesia Risks: Higher
incidence of spinal hematoma with LMWHs Infections: Meningitis,
Spinal Abscess (1/10000 with catheter < 4 days) Superficial
cellulitis: 4-14 % Catheter migration: Intrathecal, Intravascular,
subcutaneous
Neuraxial Analgesia: Intrathecal Analgesia DrugDosingComments
Clonidine 15-45 g Improves quality of blockade Epinephrine0.1-0.6
mgProlongs motor block & urinary retention Neostigmine 6.5 50 g
Motor blockade Nausea & vomiting Intrathecal Adjuvants:
Dosing
Slide 72
Peripheral Regional Analgesia Pain control superior to systemic
opioids Fewer side effects compared to systemic opioids Fewer
neurologic and infectious complications compared to neuraxial block
Prolonged duration Single injection and continuous catheter
techniques
Slide 73
Peripheral Regional Analgesia Peripheral Nerve Blockade
Indications InterscaleneRotator cuff repair, Shoulder arthroplasty,
ORIF SupraclavicularAnaesthesia to entire upper limb with single
injection Risk of pneumothorax InfraclavicularSurgery on distal
upper arm, forearm, wrist and hand AxillarySurgery distal to elbow
Separate block for musculocutaneous and intercostobrachial nerves
required MidhumeralSurgery of forearm, wrist and hand Provides
better block of radial nerve than axillary Indications of
peripheral Nerve Blocks
Peripheral Regional Analgesia Paravertebral Block: Suited for
thoracic, breast surgery, VATS, cholecystectomy, nephrectomy etc
Used to treat rib fracture pain Potential space, contains anterior
and posterior ramus of the spinal nerve root with white and grey
rami communicantes Single injection or continuous catheter
technique Comparable to thoracic epidural blockade No hypotension,
PONV, urinary retention
Slide 76
Peripheral Regional Analgesia Paravertebral Block
Slide 77
Peripheral Regional Analgesia Other Techniques: Rectus Sheath
Block Transversus abdominis plane block Placement of continuous
wound catheter Continuous intra-articular infusion of LA
Periarticular soft tissue injection of LA Intrapleural or
Intraperitoneal Analgesia
Slide 78
Peripheral Regional Analgesia Complications: Intravascular
injection Unintentional neuraxial spread Scalene block Lumbar
plexus block Paravertebral block Nerve Damage Incidence 1:10000
1:30000 Significant nerve damage 1:1 00 000 Direct injury,
hematoma, infection, ischemia >90% recover within 1 week 92 -97%
within 4-6 weeks, 99% within 1 year
Slide 79
Patient Controlled Analgesia Definition: Any technique of pain
management that allows the patients to manage their own analgesia
on demand Compensates for interpatient and intrapatient variability
in analgesic needs, variability of serum drug levels,
administrative delays
Slide 80
Patient Controlled Analgesia Benefits: Better patient
satisfaction Better analgesia Equivalent side effects Less demand
on nursing time Variables programmed with PCA: Bolus Dose
Incremental (demand) dose Lockout interval Background infusion
rate
Patient Controlled Analgesia Risk Factors: Pulmonary disease
OSA Renal or Hepatic dysfunction CHF Closed head injury Altered
mental status Lactating mothers
Slide 84
Non Pharmacological Methods: Benefits: Reduce opioid
requirement/side effects Attenuate activation of sympathoadrenal
system May provide postoperative analgesia Devoid of any side
effects Methods TENS Acupuncture/Acupressure Psyhological
Approaches Mechanism Spinal cord modulation Endogenous enkephalins
Useful adjuvants to pharmacological therapy
Slide 85
Special Populations: Pediatric Patients Barriers to effective
pain control in children: Myths about pain and children: Children
and infants do not feel pain Pain is not remembered Unable to tell
where it hurts Dont tell the truth about pain Difficulty in
assessment Developmental, emotional and cognitive differences
Difficulty in conceptualising and quantifying pain Fear of side
effects: Respiratory depression, addiction
Slide 86
Special Populations: Pediatric Patients Pain Assessment CRIES
scale Crying O2 requirement for SP)2 > 95% Increased vital signs
Expressions Sleeplessness Each parameter score 0-2 Useful for
neonatal postoperative pain Behavioural Observational Tools: For
neonates and children < 3 yrs Neonatal-Infant Pain Scale (NIPS)
Facial Expression Cry Breathing Pattern Arms Legs State of Arousal
Observed for 1 minute before, during & after a procedure and
numeric score applied to each NIPS > 3 implies pain Useful for
children < 1 year
Slide 87
Special Populations: Pediatric Patients Pain Assessment
Behavioural Observational Tools: For neonates and children < 3
yrs FLACC Scale Face Legs Activity Crying Consolability Each
component scored 0-2 Validated for 2 mo 7 yrs Childrens Hospital of
Eastern Ontario Scale (CHEOPS) Cry Facial Expression Verbalisation
Touching of affected part Torso movement Position of legs Validated
for children 1-7 yrs Score 4 implies pain Self report :Children
> 3 yrs Wong-Baker Faces Scale VAS
Slide 88
Special Populations: Pediatric Patients Treatment:
Pharmacological interventions similar to adults PCA/NCA Non
Pharmacological Interventions Sensory Rocking,cuddling, touching,
massaging, dim lighting, pacifiers, heat/cold application
Behavioural Distraction toys, music, videos Security object:
blanket, stuffed animals Play therapy Imagery Cognitive Prayers,
humor, relacation techniques
Slide 89
Special Populations: Elderly Patients Special Considerations:
Clinically significant reduction in intensity of pain perception
Communication, Affective, Cognitive, Social and Ideological
barriers Difficulty in assessing pain Comorbid conditions Increased
adverse effects due to untreated pain and interventions Decreased
analgesic requirement Increased sensitivity and decreased clearance
Untreated pain is an important contributor to postopearive
delerium
Slide 90
Summary Pain is both a sensation and an emotion with wide
interpersonal variations and the fifth vital sign. Untreated acute
pain leads to many detrimental physiological effects and to
chronicity. Treatment should include assessment, intervention and
reassessment. A multimodal approach targeting the various elements
of pain processing should be tried in all patients. LA based
epidural analgesia has many advantages over systemic opioid
analgesia. Inspite of the various interventions available,
postoperative pain is undertreated in a majority of patients, more
so in pediatric and geriatric populations.
Slide 91
Referrences Barash, Stoelting et al, Clinical Anaesthesia, 6 th
ed Millers anaesthesia, 6 th ed Anaesthesia and Intensive Care
Medicine. Volume 6:1 Jan 2005 Recent Advances in Anaesthesia, No.
22. Chapter 74. management of Acute Postoperative Pain Practice
Guidelines for Acute Pain management in perioperative setting.
Report by ASA task force on acute pain management. Anesthesiology
2004; 100:157381 Pharmacology and Physiology in Anaesthetic
practice, Stoelting and Miller, 4 th Edition Ganongs Review of
Medical Physiology, 22 nd edition