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UNDERSTANDING OF UNDERSTANDING OF PAINPAIN
“ Nociceptive, Neuropathic & Mixed “ Nociceptive, Neuropathic & Mixed Pain ”Pain ”
Department of Anesthesiology, Department of Anesthesiology, Intensive Care and Pain Management Intensive Care and Pain Management
Faculty of Medicine Faculty of Medicine University of Hasanuddin University of Hasanuddin
MakassarMakassar
ObjectiveObjectiveAfter this lecture, participants After this lecture, participants are able to understand :are able to understand :1.1.Definition of PainDefinition of Pain2.2.Mechanism of Pain perceptionMechanism of Pain perception3.3.Nociceptive PainNociceptive Pain4.4.Neuropathic PainNeuropathic Pain5.5.Mixed PainMixed Pain6.6.Chronic PainChronic Pain7.7.Take Home MessangeTake Home Messange
Before Eve was created from Adam's Rib, Adam was put into sleep
Pain was faithfully transmittedfrom periphery to brain
First ideas….
A pure stimulus response relationship
Descartes (17th Century)
Progress in understanding painProgress in understanding pain
1965-
MELZACK and WALL MELZACK and WALL ‘Gate Control Theory’ ‘Gate Control Theory’
DHN
GATE CONTROL SYSTEM
+
+ ACTIONSYSTEM
Brain
SG+
-
-
-
Aβ
C
1965 MELZACK and WALL 1965 MELZACK and WALL Introduce Hypothesis ofIntroduce Hypothesis of
““GATE CONTROL THEORY”GATE CONTROL THEORY”
The beginning of “MODULATION”
ScientificScientific :: Pain is unpleasant sensory and Pain is unpleasant sensory and emotional experience ascociated emotional experience ascociated
with with actual or potential tissue damage actual or potential tissue damage or or describe in term of such damage. describe in term of such damage.
(Merskey (Merskey ,accepted by IASP 1979),accepted by IASP 1979)
ClinicalClinical :: “Pain is whatever the “Pain is whatever the experiencing experiencing person says. (Mc Caffery 1997)person says. (Mc Caffery 1997)““Pain is whatPain is what ever ever the pateint says” the pateint says”
Definition of PainDefinition of Pain
From this definition, some conclusions can be From this definition, some conclusions can be obtained;obtained;
1.1. PHYSIOLOGICAL PAINPHYSIOLOGICAL PAIN, , is a normal sensation, elicited is a normal sensation, elicited by potential tissue damage by potential tissue damage Withdrawal reflex Withdrawal reflex
2.2. PATHOPHYSIOLOGICAL PAINPATHOPHYSIOLOGICAL PAIN, is an abnormal sensation :, is an abnormal sensation : Due to actual tissue damage Due to actual tissue damage inflamed pain = clinical inflamed pain = clinical
pain = acute pain e.g. : postoperative painpain = acute pain e.g. : postoperative pain Due to nervous system damage Due to nervous system damage neuropathic pain neuropathic pain
3.3. PATHOLOGICAL PAINPATHOLOGICAL PAIN,, Described in intern of such damage Described in intern of such damage CHRONIC PAIN CHRONIC PAIN Chronic pain is now consider as Chronic pain is now consider as ““a disease of entitya disease of entity””. .
Causing suffering, reducing QOLCausing suffering, reducing QOL
KLASIFIKASI NYERIKLASIFIKASI NYERI
Menurut waktu Nyeri akut & kronik
Menurut patofisiologinya : Nyeri fisiologik Nyeri klinis ( nyeri patofisiologik)
1. Nyeri nosiseptif2. Nyeri neuropatik
• Perifer• Sentral
3. Nyeri psikogenik / idiopatik
N Y E R I
Acute PainAcute Pain
Acute PainAcute Pain is is the normal the normal predicted physiological response predicted physiological response to an adverse chemical, thermal to an adverse chemical, thermal or mechanical stimulus …., or mechanical stimulus …., associated with surgery, trauma associated with surgery, trauma and acute illness.”“ and acute illness.”“
( Federation of State Medical Boards of US )
Acute painAcute pain
Acute onsetAcute onset, , localized, sharp and high localized, sharp and high intensity painintensity pain..
Usually self limitingUsually self limiting. . Signs of physiologic response of various Signs of physiologic response of various
organs or systems, e.g. sweating, palpitation organs or systems, e.g. sweating, palpitation and increased of blood pressureand increased of blood pressure. .
Identifiable causes or related to injury or Identifiable causes or related to injury or diseasesdiseases
(Pain of recent onset and probable limited duration, IASP)
Causes of acute painCauses of acute pain
TraumaTrauma SurgerySurgery DeliveryDelivery Invasive medical Invasive medical
proceduresprocedures Acute illnessAcute illness..
Acute PainAcute Pain
constantconstant sharp achingsharp aching well localizedwell localized
constant dull aching poorly localized usually with nausea and
vomitoccasional colicky or cramp often referred to cutaneous sites
Somatic pain
Visceral pain
Referred PainReferred Pain
Figure 10-13: Referred pain
Dorsal HornDorsal root
ganglion
Peripheral sensoryNerve fibers
A
A
C
Largefibers
Smallfibers
There are two sensory afferent neurons1. Large myelinated A fibers, very fast conduction velocity.
Respond to innocuous stimuli 2. Small myelinated A & C unmyelinated fibers, have slow
conduction velocity. Respond to noxious stimuli
DHN
PAININNOCUOUS SENSATION
NOXIOUS STIMULUS
INNOCUOUS STIMULUS
DHN
TouchTactilePressure
Physiological Pain
A C fiber A
First PainSecond Pain
Pain Afferent neuronsPain Afferent neuronsA myelinated fiber
C unmyelinated fiberResponds to noxious stimuli
Both have free nerve endings
Naciceptors(receptor
Nyeri)
NociceptorsNociceptors1.1. Mechanothermal nociceptorsMechanothermal nociceptors
Respond to mechanical and thermal stimuli.Respond to mechanical and thermal stimuli. display rapid conduction.display rapid conduction. Produced first pain and well localized.Produced first pain and well localized. Ad fibers respond to this naciceptors.Ad fibers respond to this naciceptors.
2.2. Polimodal nociceptorsPolimodal nociceptors Respond to mechanical, thermal and chemical.Respond to mechanical, thermal and chemical. Slow conduction.Slow conduction. Produced second pain and diffuse.Produced second pain and diffuse. C fibers respond to this receptor.C fibers respond to this receptor.Exist in many tissues, skin, muscle, pariosteum, joints, and viscera, Exist in many tissues, skin, muscle, pariosteum, joints, and viscera, except brain. except brain.
Between noxious stimulus and Between noxious stimulus and perception of pain lies a complex perception of pain lies a complex series of electrophysioloc event, series of electrophysioloc event,
collectively termed collectively termed NOCICEPTIONNOCICEPTION 4 physiologic processes are 4 physiologic processes are
involved:involved:1. Transduction1. Transduction 2. Transmission2. Transmission
3. Modulation3. Modulation4. Perception4. Perception
NOCICEPTION
Process whereby Process whereby noxious stimuli noxious stimuli are translated are translated into electrical into electrical activity at the activity at the sensory endings sensory endings of nerveof nerve
Heat
Chemical
TRANSDUCTION
TRANSDUCTION
Pressure
K+ K+
Ca2+
Na+
1. Transduction
4. Transmitter Release2. Spike Initiation
3. Propagation
Modified Meliala, 2006
Transduction Process
Heat
Cold
Intense
ForceMechanical
Heat
Cold
PainAutonomic Response
Withdrawal Reflex
Nociceptor sensory neuron
NOCICEPTIVE PAINNoxious Peripheral Stimuli
Spinal cord
Brain
Modification Meliala, 2005
TRANSMISSIONTRANSMISSION Propagation of impulses Propagation of impulses
throughout the sensory throughout the sensory nervous system. Ornervous system. Or
Passage of signal from Passage of signal from periphery to the central periphery to the central NS.NS.
A
A
CLateral
Nucleusproprius
Marginal layer Substantiagelatinosa
Medial
Afferent Synaptic in DHN
Medula SpinalisMedula SpinalisDahulu Dahulu :: dikenal sebagai dikenal sebagai
“SIMPLE RELAY STATION” Untuk “SIMPLE RELAY STATION” Untuk transmisi Nyeritransmisi Nyeri
SekarangSekarang :: Sebagai tempat Sebagai tempat interaksi yanginteraksi yangkompleks antara kompleks antara
Serabut-serabut Eksitatori Serabut-serabut inhibitori
MODULASI NYERIMODULASI NYERI
Serabut Eksitatori & Serabut Eksitatori & InhibitoriInhibitori
OTAKWDR & NS
Glutamate (Subs P)
GABAGlycineOpioidsNA, 5HT
C
Glutamate Glutamate
Serabut
Inhibitori
Serabut Eksitatori
MODULATIONMODULATION
The process whereby The process whereby endogenous analgesic system endogenous analgesic system (opioid, serotonergic, and (opioid, serotonergic, and noradrenergic) can modify noradrenergic) can modify nociceptive transmissionnociceptive transmission
Spinal CordSpinal CordSPINAL CORD (DHN)SPINAL CORD (DHN) is the key point of is the key point of
modulationmodulation The place where afferent input is processed.The place where afferent input is processed. Where interaction between excitatory and Where interaction between excitatory and
inhibitory system.inhibitory system. NOCICEPTION IS BORN IN DORSAL NOCICEPTION IS BORN IN DORSAL
HORN, BUT WE DON’T CALL IT PAIN TILL HORN, BUT WE DON’T CALL IT PAIN TILL IT REACHES THE BRAIN (Dr. Ken Casey)IT REACHES THE BRAIN (Dr. Ken Casey)
Modulation
Descending Modulating Descending Modulating PathwaysPathways
CEREBRAL CORTEXCEREBRAL CORTEX THALAMUSTHALAMUS MIDBRAIN/ BRAINSTEMMIDBRAIN/ BRAINSTEM
Periaqueductal gray (PAG)Periaqueductal gray (PAG) Nuclei raphe magnus (NRM)Nuclei raphe magnus (NRM) Locus ceruleus (LC)Locus ceruleus (LC) Sub ceruleusSub ceruleus
SPINAL CORDSPINAL CORD
Ascending pathways is modulated by descending modulating pathways in several higher centers;
SEROTONINNEOREPINEPHRINE
Noxious/ Innocuous
Modulation
InhibitoryFacilitatory/ excitatory
No PainPain
Two Kind Two Kind of Stimuliof StimuliNociceptor
DHN
Pain stimulus is not perfect terminology
Pain
CNS
Nociception
InhibitionExcitation
Pain
CNS
Nociception
InhibitionExcitation
Example: Stress Induced Analgesia
X
Nociception Without Nociception Without PainPain
Pain
CNS
Nociception
InhibitionExcitation
Example: Phantom ,neurophatic painX
Pain Without Pain Without NociceptionNociception
Depends on the balance between:Excitatory systemExcitatory systemInhibitory systemInhibitory system
(Cognitive, emotional, behavior)(Cognitive, emotional, behavior)
Pain PerceptionPain Perception
Beecher
Pain perception depend on the meaning of injury
Pain Pain PerceptionPerception
SpinothalamicSpinothalamictracttract PeripheralPeripheral
nervenerve
Dorsal HornDorsal Horn
Dorsal root Dorsal root ganglionganglion
PainPain
MedulationMedulation
TransductionTransduction
AscendingAscendinginputinput
DescendingDescendingmodulationmodulation
PeripheralPeripheralnociceptorsnociceptors
TraumaTrauma
Adapted from Gottschalk A et al. Am Fam Physician. 2001;63:1981, and Kehlet H et al. Anesth Analg. 1993;77:1049.
PerceptionPerception
transmissiontransmission
PainPerception Brain
PerceptionPerceptionFinal process Final process to create the to create the final subjective final subjective and emotional and emotional experience that experience that we call painwe call pain
Perception
How pain perception is processed, no body knows and Where pain perceptions in the brain still unclear.
What is nociceptive pain?What is nociceptive pain?
Painful region is typically localized at the site of injury – often described as throbbing, aching or stiffness
Usually time-limited and resolves when damaged tissue heals (e.g. bone fractures, burns and bruises)
A sensory experience that occurs when specific peripheral sensory neurons (nociceptors) respond to noxious stimuli
Responds to conventional analgesics
Can also be chronic (e.g. osteoarthritis)Can also be chronic (e.g. osteoarthritis)
Heat
Cold
Intense
ForceMechanical
Heat
Cold
PainAutonomic Response
Withdrawal Reflex
Nociceptor sensory neuron
NOCICEPTIVE PAINNoxious Peripheral Stimuli
Spinal cord
Brain
Modification Meliala, 2005
Histamine
Leukotriens
TISSUE INJURY
NSAID (Cox1 or Cox2)
PAIN
BradykininProstaglandins
ProstaglandinsProstaglandins produced in response produced in response to tissue injury; to tissue injury; increase sensitivity of increase sensitivity of nociceptor nociceptor ((pain)pain)
Nociceptor then releases substance P, which dilates blood vessels and increases release of inflammatory mediators, such as Bradykinin (redness & heat)
Substance P also promotes degranulation of mast cells, which release histamine (swelling)
1
2
3
Pain-sensitive tissue
Painful stimulus
Prostaglandin
Substance P
Histamine
Mast cellBlood vessel
Bradykinin
Nociceptor
Substance P
23
1
Inflammation TissueInflammation Tissue
SensitizationSensitization
Gottschalk A et al. Am Fam Physician. 2001;63:1979-84.
InjuryInjury
Pain
Inte
nsity
10
8
6
4
2
0
Stimulus Intensity
NormalPain
Response
Allodynia
Hyperalgesia
Hyperalgesia—heightened sense of pain to noxious stimuli
Allodynia—pain resulting from normally painless stimuli
DHN
PAIN
CLINICAL PAIN
PNSCNS
Ab FiberAd Fiber
Hyperexitable DHN
(INFLAMATION PAIN)Low Intensity Stimulus
What is neuropathic What is neuropathic pain?pain?
Pain caused by a primary lesion or dysfunction in the peripheral or Pain caused by a primary lesion or dysfunction in the peripheral or central nervous systemcentral nervous system
Pain often described as shooting, electric shock-like or burning.
The painful region may not necessarily be the same as the site of injury.
Almost always a chronic condition (e.g. postherpetic neuralgia, poststroke pain)
Responds poorly to conventional analgesics
Neurophatic Pain Neurophatic Pain is……?is……?
1.1. No pain mechanism is inevitable No pain mechanism is inevitable consequence of a particular diseaseconsequence of a particular disease
2.2. One mechanism could be responsible One mechanism could be responsible of many different symptomsof many different symptoms
3.3. Same symptom may be caused by Same symptom may be caused by different mechanismdifferent mechanism
4.4. More one mechanism can operate in More one mechanism can operate in a single patient a single patient (There mechanism may change (There mechanism may change with time)with time)
Ectopic dischargesEctopic dischargesNerve lesion induces hyperactivity due to changes in ion channel function
Ectopic discharges
Nerve lesion
Spinal cordNociceptive afferent fiber
Descendingmodulation
Ascendinginput
Perceived pain
Loss of inhibitory Loss of inhibitory controlscontrols
Loss of descending modulation causes exaggerated pain due to an imbalance between ascending and descending signals
Nociceptive afferent fiber
Noxiousstimuli
Ascendinginput
Spinal cord
Loss ofdescendingmodulation
Exaggerated painperception
Intact tactile fiber
Central sensitizationCentral sensitizationAfter nerve injury, increased input to the dorsal horn can induce central sensitization
Perceived pain
Ascendinginput
Descendingmodulation
Nerve lesion
Nociceptive afferent fiber
Tactilestimuli
Perceived pain(allodynia)
Ascendinginput
Descendingmodulation
Abnormal discharges induce central sensitization
Recognition of neuropathic Recognition of neuropathic painpain
Examples• Diabetic peripheral neuropathy (DPN)• Postsurgical nerve injury• Postherpetic neuralgia (PHN)• Lumbar radiculopathy• Poststroke pain
Common descriptors• Shooting• Electric shock-like• Burning• Tingling• Numbness
Neuropathic painPain initiated or caused by a primary
lesion or dysfunction in the peripheral or central nervous system
The co-presentation of The co-presentation of nociceptive and neuropathic nociceptive and neuropathic
painpain
Both types ofpain co- exist in
many conditionsNeuropathic painNociceptive pain
Co-existence of Co-existence of nociceptive and nociceptive and
neuropathic painneuropathic pain
• Examples include low back pain associated with radiculopathy, cancer pain and carpal tunnel syndrome
• Effective management requires a broader therapeutic approach to relieve both the nociceptive and neuropathic pain components
• Co-existence of pain types has been referred to as eithera “mixed” or “combined” pain state
Example of co-existing pain: Example of co-existing pain: herniated disc causing low herniated disc causing low
back pain and lumbar back pain and lumbar radiculopathyradiculopathy
Lumbarvertebra
Disc herniation
Activation of peripheral nociceptors –cause of nociceptive pain component
Compression and inflammation of nerve root – cause of neuropathic pain component
Example of co-existing pain: Example of co-existing pain: herniated disc causing low herniated disc causing low
back pain and lumbar back pain and lumbar radiculopathyradiculopathy
Lesion
Activationof local
nociceptors
Constant ache, throbbingpain in the low back
Patient presentswith both types
of pain
Shooting, burningpain in the foot
Ectopic dischargesfrom nerveroot lesion
Example of co-existing pain: Example of co-existing pain: herniated disc causing low herniated disc causing low
back pain and lumbar back pain and lumbar radiculopathyradiculopathy
Nociceptive and neuropathic Nociceptive and neuropathic pain maypain may
co-exist in low back pain co-exist in low back pain conditionsconditions Neuropathic pain componentNociceptive pain component
ExamplesPeripheral• Postherpetic neuralgia• Trigeminal neuralgia• Diabetic peripheral neuropathy• Postsurgical neuropathy• Posttraumatic neuropathyCentral• Poststroke painCommon descriptors2
• Burning• Tingling• Hypersensitivity to touch or cold
Examples • Pain due to inflammation• Limb pain after a fracture• Joint pain in osteoarthritis• Postoperative visceral pain Common descriptors2
• Aching• Sharp• Throbbing
Examples • Low back pain with
radiculopathy• Cervical
radiculopathy• Cancer pain• Carpal tunnel
syndrome
Mixed PainPain with
neuropathic and nociceptive components
Neuropathic PainPain initiated or caused by a
primary lesion or dysfunction in the nervous system (either peripheral or
central nervous system)1
Nociceptive PainPain caused by injury to
body tissues (musculoskeletal,
cutaneous or visceral)2
PRESENTATION ACROSS PAIN STATES VARIESPRESENTATION ACROSS PAIN STATES VARIES
1. International Association for the Study of Pain. IASP Pain Terminology.2. Raja et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed. 1999.;11-57
Chronic pain ?Chronic pain ?
Chronic painChronic pain is a pain that persists is a pain that persists beyond normal tissue healing time, beyond normal tissue healing time, which is assumed to be three months.which is assumed to be three months.
The International Association for study of pain (IASP)The International Association for study of pain (IASP)
panthom pain
Pathophysiology in CNS - Pathophysiology in CNS - ““central central sensitizationsensitization””
““RewiringRewiring” ” in spinal cord dorsal hornin spinal cord dorsal horn Genetic changesGenetic changes in dorsal horn neurons in dorsal horn neurons Death of neuronsDeath of neurons: inhibitory deficit: inhibitory deficit InhibitionInhibition of normal motor activity, muscle of normal motor activity, muscle
wastingwasting Sympathetic dysfunctionSympathetic dysfunction, tropic changes, tropic changes
PATHOPHYSIOLOGY PATHOPHYSIOLOGY OF CHRONIC PAINOF CHRONIC PAIN
CONSEQUENCE of CONSEQUENCE of CHRONIC PAINCHRONIC PAIN
Fear - Fear - avoidance behaviouravoidance behaviour AnxietyAnxiety and sleep disturbance and sleep disturbance DepressionDepression, helplessness, irritability, , helplessness, irritability,
suicidal risksuicidal risk CNS toxicityCNS toxicity due to inappropriate drug due to inappropriate drug
useuse Loss of jobLoss of job, family and community status, family and community status
CHRONIC PAIN IS A CHRONIC PAIN IS A DISEASE ENTITYDISEASE ENTITY
Is a major problem of public healthIs a major problem of public health lead to emotional distress and suffering lead to emotional distress and suffering
(insomnia, anxiety, depression,can not work, etc)(insomnia, anxiety, depression,can not work, etc)
Is really a killer for quality of lifeIs really a killer for quality of life
ConclutionConclution1.1. -Pain is a very subjective feeling-Pain is a very subjective feeling
-Pain is what ever the patient says-Pain is what ever the patient says2.2. -Only nociceptive pain is respond to NSAID -Only nociceptive pain is respond to NSAID
(cox1 or cox2)(cox1 or cox2)3. 3. -Neurophatic pain do not respond to NSAID -Neurophatic pain do not respond to NSAID
but it may respond to antidepressants or but it may respond to antidepressants or anticonvulsants may be opioid.anticonvulsants may be opioid.
4. 4. - Chronic pain, is pain beyond naciceptive, - Chronic pain, is pain beyond naciceptive, occur after healing process, difficult to occur after healing process, difficult to treat and reduced quality of life.treat and reduced quality of life.
It’s important to more It’s important to more understanding PAIN, type and understanding PAIN, type and characteristic of pain..characteristic of pain..
Because…Because…
In many parts of Indonesia : In many parts of Indonesia : Many people may die in pain, but Many people may die in pain, but Many more people dying with pain, Many more people dying with pain, Even many more people living in painEven many more people living in pain
This is our task to help them as a Doctor This is our task to help them as a Doctor
Take Home Message
TO CURE IS SOMETIMESTO CURE IS SOMETIMES TO TREAT IS OFTENTO TREAT IS OFTEN TO COMFORT IS ALWAYSTO COMFORT IS ALWAYS
The task of a doctor:The task of a doctor:
A. Pare (1598)A. Pare (1598)
