the evolving concept of pain dr e. frohlich march 2005 gemp iii
TRANSCRIPT
The evolving The evolving concept of painconcept of pain
Dr E. FrohlichDr E. FrohlichMarch 2005March 2005GEMP IIIGEMP III
Pain Pain
most frequent cause of suffering andmost frequent cause of suffering and
Disability.Disability.
Seriously impairing quality of life inSeriously impairing quality of life in
millions of people around the globe. millions of people around the globe.
Acute easy to understand.Acute easy to understand.
Chronic ? Chronic ?
Epidemiological data:Epidemiological data:
Annually in the USAAnnually in the USA
15-20% population 15-20% population suffer acute pain suffer acute pain
25-30% -suffer chronic 25-30% -suffer chronic painpain
Traditional Clinico - pathological training Traditional Clinico - pathological training PAIN = SYMPTOMPAIN = SYMPTOM warning of serious illness or pathology.warning of serious illness or pathology.
Chronic pain = Often no pathology foundChronic pain = Often no pathology found
Examinations, investigations to establish Examinations, investigations to establish
responsible pathologyresponsible pathology
time consuming expensivetime consuming expensive delay treatment.delay treatment.
Pain Pain Universal described throughout historyUniversal described throughout history
Egyptians related pain to Egyptians related pain to injuryinjury
Plato - referred to pain as an Plato - referred to pain as an EMOTIONEMOTION
GENESIS GENESIS Pain = grief, sorrowPain = grief, sorrow Linking physical to emotionalLinking physical to emotional
Decartes-(17Decartes-(17thth century) century)
Separate biological fromSeparate biological from
EmotionalEmotional
Nociceptors Nociceptors →→
RopeRope → →
BellBell
19 th century19 th century 2 physiological2 physiological theories developed theories developed 1. Specificity (sensory) 1. Specificity (sensory) 2. Intensity (summation) 2. Intensity (summation)
BY end of the 19th centuryBY end of the 19th century
physiologistsphysiologists
MIND AND BODY ARE SEPARATE MIND AND BODY ARE SEPARATE
PSYCHOLOGY PSYCHOLOGY
separated from separated from
NEUROLOGY NEUROLOGY psychologistspsychologists
Unfortunate separation (Bio-Psycho-Social)Unfortunate separation (Bio-Psycho-Social)BUT BUT leading to the leading to the differentiationdifferentiation between between NOCICEPTION and PAINNOCICEPTION and PAIN
NOCICEPTION NOCICEPTION ≠ ≠ PAIN PAIN
-GA, LA-GA, LA-Trauma (Endorphine, Psychological?)-Trauma (Endorphine, Psychological?)-Beecher (2-Beecher (2ndnd world war) world war)-Denervation (Nociception reaching brain as -Denervation (Nociception reaching brain as
evidenced by sympathetic response.)evidenced by sympathetic response.)
NOCICEPTION WITH NO PAINNOCICEPTION WITH NO PAIN -GA- PAIN NEEDS CONCIOUSNESS-GA- PAIN NEEDS CONCIOUSNESS -LA-LA -Trauma, Beecher’s report,-Trauma, Beecher’s report,
PAIN with no NociceptionPAIN with no Nociception -Chronic pain -Chronic pain CRPS, NEUROPATHICCRPS, NEUROPATHIC PHANTOM LIMBPHANTOM LIMB -PHN,HIV, Multiple sclerosis-PHN,HIV, Multiple sclerosis
The 20th centuryThe 20th century
The gate control theoryThe gate control theory
1965 Melzack and Wall integrated 1965 Melzack and Wall integrated
-specialization of receptors -specialization of receptors
- central summation - central summation
- patterning and modulation - patterning and modulation
- influence of psychological factors. - influence of psychological factors.
GATE THEORY GATE THEORY Specificity theorySpecificity theorySpecialized Nociceptors- - YESSpecialized Nociceptors- - YES
Skin to brain-straight throughSkin to brain-straight through Push button? - NOPush button? - NO
Summation theorySummation theoryIntensity of stimulus ≠ pain perceptionIntensity of stimulus ≠ pain perceptionAmount and quality of pain determined byAmount and quality of pain determined byphysiological and psychological variablesphysiological and psychological variables
Pain not limited to specific Nociceptive pathways Pain not limited to specific Nociceptive pathways Result of Result of
Activity in several interactingActivity in several interacting pathwayspathways..
Gate control theoryGate control theory Central controlCentral control
Large diameter - Large diameter -
excitatory + actionexcitatory + action
systemsystem
inhibitory - +inhibitory - +
Small diameter Small diameter
SG
Central transmission
cells
gate controlgate control
The gate theoryThe gate theory
No Nociceptive pathwaysNo Nociceptive pathways
Transmission cells in spinal cord getTransmission cells in spinal cord get
excited or inhibited by large or small fibersexcited or inhibited by large or small fibers
19821982
Gate theory modified to include Gate theory modified to include
inhibitory inhibitory descendingdescending
mechanisms from brainstemmechanisms from brainstem
IASP IASP Pain Pain DefinitionDefinition
UnpleasantUnpleasant sensory sensory AND AND emotional emotional sensation. sensation. Associated with Associated with Actual Actual OR OR potentialpotential tissue damage. tissue damage. OR described in such terms.OR described in such terms.
Pain = Pain = Bio- Psycho- Social PhenomenonBio- Psycho- Social Phenomenon
PAIN ≠ NOCICEPTION ≠ PAINPAIN ≠ NOCICEPTION ≠ PAIN
Pain is always subjective, always Pain is always subjective, always personal.personal.
Pain expression and pain behavior depend Pain expression and pain behavior depend on cultural and environmental factors. on cultural and environmental factors.
There are more similarities then There are more similarities then differences between cultures /sexes re differences between cultures /sexes re experience of pain.experience of pain.
acute painacute pain
Acute pain (musculoskeletal / visceral organs.)Acute pain (musculoskeletal / visceral organs.)
- - signal signal for tissue damage, for tissue damage, protectiveprotective
phenomenon.phenomenon.
-prompts -prompts withdrawalwithdrawal, flight or fight sympathetic , flight or fight sympathetic
response, response, inflammation inflammation and and healing.healing.
-Therapy-Therapy is usually is usually effective.effective.
Acute pain/ injury Acute pain/ injury
well understood andwell understood and acceptedaccepted
by patient/Dr/societyby patient/Dr/society
Somatic pain differs from visceral pain in Somatic pain differs from visceral pain in
qualityquality and and localizing localizing ability. ability.
cutaneouscutaneous pain - from ectoderm, pain - from ectoderm,
-well localizes , sharp in nature. -well localizes , sharp in nature.
-Cutaneous tenderness, -Cutaneous tenderness,
-Hyperalgesia -primary / secondary -Hyperalgesia -primary / secondary
-Allodynia.-Allodynia.
Deep somaticDeep somatic structures structures (bone, periosteum, muscle tendon fascia) mesoderm(bone, periosteum, muscle tendon fascia) mesoderm
- less well localized - less well localized
- mimic visceral pain. - mimic visceral pain.
-pain can be referred/ radiate -pain can be referred/ radiate
-cause cutaneous hyperalgesia ,-cause cutaneous hyperalgesia ,
-provoke autonomic responses -provoke autonomic responses
and reflex muscle spasmand reflex muscle spasm
Visceral Visceral pain - Endodermal pain - Endodermal
viscera or peritoneum/pleuraviscera or peritoneum/pleura..
- Dull aching ,diffuse and poorly localizedDull aching ,diffuse and poorly localized
- autonomic phenomena autonomic phenomena
(sweating, nausea,bradycardia).(sweating, nausea,bradycardia).
Neurophysiologic endocrine and metabolic Neurophysiologic endocrine and metabolic response to injury:response to injury:
↑↑sympathetic tone- sympathetic tone- ↑ ↑ HR, CO,BP myocardial work.HR, CO,BP myocardial work. ↑ ↑ metabolic rate and 02 consumptionmetabolic rate and 02 consumption ↓ ↓ GI tone and motility (↓gastric emptying, GI tone and motility (↓gastric emptying, ileus)ileus) -↓ Urinary tract tone →urinary retention-↓ Urinary tract tone →urinary retention -↑skeletal muscle tone -↑skeletal muscle tone spasm spasm -↑ catabolism, hyperglycemia-↑ catabolism, hyperglycemia
ANXIETY, FEAR AND SUFFERINGANXIETY, FEAR AND SUFFERING
General considerations of chronic painGeneral considerations of chronic pain
Arbitrary definition- Arbitrary definition- -more then 3-6 months. -more then 3-6 months.
-The pain Outlasts the noxious stimulus and -The pain Outlasts the noxious stimulus and often the stimulus can not be identified. often the stimulus can not be identified.
Traditionally referred to as Traditionally referred to as cancer / non cancer related.cancer / non cancer related.
Viewed as a disease on its own rightViewed as a disease on its own right not a symptomnot a symptom.. Like any other disease it has specific : Like any other disease it has specific :
Peripheral Bio 1Peripheral Bio 1stst analgesics analgesics
Central Psycho 2Central Psycho 2ndnd analgesics analgesics
Metabolic SocialMetabolic Social
Inflammatory l surgical inter-Inflammatory l surgical inter-
Neuropathic -ventionsNeuropathic -ventions
Traumatic/neoplasticTraumatic/neoplastic
CHRONIC PAIN
ETIOLOGY SIGNS & SYMPTOMS TRETMENT
1982 Loeser published a conceptual 1982 Loeser published a conceptual model of the patient with pain.model of the patient with pain.
PAIN BEHAVIOR
SUFFERING
PAIN
NOCICEPTION
PAIN BEHAVIORPAIN BEHAVIOR
NeuroplasticityNeuroplasticity Experiences can change synapses and Experiences can change synapses and intracellular expressions. intracellular expressions. CNS LEARNS FROM EXPERIENCECNS LEARNS FROM EXPERIENCE
Information does not simply move through. Information does not simply move through.
changes in changes in neurotransmitter signals, neurotransmitter signals, Receptor expressionReceptor expression nature and number of synapses ,nature and number of synapses , neuronal structure and neural circuits ,neuronal structure and neural circuits , NERVOUS SYSTEM ADAPTS TO INFORMATION AND CHANGES NERVOUS SYSTEM ADAPTS TO INFORMATION AND CHANGES WITH IT. WITH IT.
....
NEUROTRANSMITTERSNEUROTRANSMITTERS
ExcitatoryExcitatory
Subst P, Neurokinine 1, GlutamateSubst P, Neurokinine 1, Glutamate
Activate AMPA receptorActivate AMPA receptor
Sensitize NMDASensitize NMDA
Acting on nervous system -Central Acting on nervous system -Central
-peripheral.-peripheral.
central sensitization, wind upcentral sensitization, wind up
Long Tem Potentiation and modulation. Long Tem Potentiation and modulation.
InhibitoryInhibitory
GlycinGlycin GABAGABA EndorphinesEndorphines NENE SerotoninSerotonin SomatostatinSomatostatin
ReceptorsReceptors
Opiate Opiate
At spinal AND supraspinal levelAt spinal AND supraspinal level
AND peripheryAND periphery
Receptors Ligands Receptors Ligands
μμ ββ Endorphines Endorphines
δδ Enkephalines Enkephalines
κκ Dynorphine Dynorphine
excite inhibitory neuronsexcite inhibitory neurons
ANALGESIA AND ANTIHYPERALGESIAANALGESIA AND ANTIHYPERALGESIA
Different mechanismsDifferent mechanisms
Opioids - Opioids -
not prevent central sensitizationnot prevent central sensitization
not have antihyperalgesic effectsnot have antihyperalgesic effects
Mu receptor agonistsMu receptor agonists
produce hyperalgesiaproduce hyperalgesia
BuprenorphineBuprenorphine
partial Mu agonist partial Mu agonist
K and Delta antagonistK and Delta antagonist
COX inhibitors- produce antihyperalgesiaCOX inhibitors- produce antihyperalgesia
Ketamine - antihyperalgesiaKetamine - antihyperalgesia
RECEPTORSRECEPTORS GABA - in brain and SCGABA - in brain and SC
GABA A GABA BGABA A GABA B
Ligand GABA GABALigand GABA GABA
BaclofenBaclofen
Function inhibitory Ca K Function inhibitory Ca K
ChannelsChannels
Modulated BenzoModulated Benzo
By BarbiturateBy Barbiturate
SteroidsSteroids
AnaestheticsAnaesthetics
Transient receptorsTransient receptors
VR1VR1
VRL-1 Vaniloid receptor like VRL-1 Vaniloid receptor like
Voltage gated channels, Voltage gated channels,
detect noxious heatdetect noxious heat
f MRIf MRI
Superficial Superficial versus versus deep somatic paindeep somatic pain..
Stimulate different areas of the brain.Stimulate different areas of the brain.
Deep somatic in brain area linked to Deep somatic in brain area linked to depressive withdrawn behavior.depressive withdrawn behavior.
Ion channels – Ion channels – Target for analgaesics Target for analgaesics
(GABA(A)) inhibitory(GABA(A)) inhibitoryAndAndNMDA – Excitatory receptorsNMDA – Excitatory receptorscomplex ion channels complex ion channels
Ligands regulate Voltage gated Ligands regulate Voltage gated Ca channels targets forCa channels targets foranalgesics analgesics
AntiepilepticsAntiepileptics
work via three major mechanisms work via three major mechanisms
--Block of voltage-activated Na channels.Block of voltage-activated Na channels.
-Potentiation of GABA -Potentiation of GABA
-Reduction of glutamate excitatory-Reduction of glutamate excitatory
transmission.transmission.
Ketamine Ketamine
Blocks -Blocks -sodiumsodium channels channels
-voltage-gated -voltage-gated potassiumpotassium channels channels
blocks NMDA receptor blocks NMDA receptor
ANALGESIAANALGESIA
++
ANTI-HYPERALGESIAANTI-HYPERALGESIA
ReducesReduces
excitability in superficial dorsal hornexcitability in superficial dorsal horn
NOVEL DRUGSNOVEL DRUGS
Ziconotide – Marine snail toxinZiconotide – Marine snail toxin
N-type voltage-gated N-type voltage-gated Ca channelCa channel blocker, blocker,
preventing the conduction of nerve signals. preventing the conduction of nerve signals.
Narrow therapeutic window, lag time for Narrow therapeutic window, lag time for onsetonset
offset of analgesia and adverse events.offset of analgesia and adverse events.
severe psychiatric and central nervous severe psychiatric and central nervous system adverse effects.system adverse effects.
Activation of GLIAL cellsActivation of GLIAL cells
Nerve growth factor - NGFNerve growth factor - NGF
Role in pain generation Role in pain generation
hyperalgesiahyperalgesia
Expressed in injured tissueExpressed in injured tissue
NGF antagonists – being developedNGF antagonists – being developed
Take home messageTake home message- Continuously evolving.Continuously evolving.- Concept changing from - Concept changing from dualisticdualistic to to integrativeintegrative.. (mind - body.)(mind - body.)- CNS undergoes CNS undergoes structuralstructural changes - Not changes - Not
static. static. - Chronic pain is a Chronic pain is a disease on its own rightdisease on its own right RequiringRequiring multidisciplinary approachmultidisciplinary approach, , aiming to improve aiming to improve COPINGCOPING not eliminate painnot eliminate pain..
We are only beginning to understand painWe are only beginning to understand pain
MechanismSMechanismS
Receptor agonists antagonists, Receptor agonists antagonists, channelopathies, genetic factorschannelopathies, genetic factors
Grouping of different pains according to their Grouping of different pains according to their mechanism of action will provide means for mechanism of action will provide means for specific Rx and management.specific Rx and management.