definition of pain (iasp) “an unpleasant sensory and emotional experience associated with actual...
TRANSCRIPT
Definition of Pain (IASP)“An unpleasant sensory and emotional
experience associated with actual or potential tissue damage, or described in terms of such
damage.”
Nociception and Pain
Nociception vs Pain
*Nociceptors are a specific subset of peripheral sensory organs which respond to noxious stimuli.
•Tranduction*•Conduction•Spinal Processing•Perception
PhysiologicalClinical
Persistent
Categories of Pain
Physiological Pain1. “Fast” pain – carried by A fibers
• Sharp• Well-localized
2. “Slow” pain – carried by C fibers• Aching• Poorly localized
ATP P2X2 Glutamatenucleus
Heat VR1
H+ ASIC
Bradykinin
Nociceptor Activation
VR1= vanilloid receptorASIC=acid sensing ion channelsP2X2=purinergic receptor
Mechanical
Ca+2
PKA/PKC ?Na+/Ca+2
Nociceptors in Teeth
1. A fibers thermoreceptors mechanoreceptor
2. C fibers polymodal (chemoreceptors)
Hydrodynamic Mechanism of Dental Pain
A. OdontoblastB. PredentinC. DentinD. Odontoblastic ProcessE. Subodontoblastic Nerve PlexusF. A FiberG. Axon Terminal in Tubule
Substantia Gelatinosa
Spinal Processing
1. Nociceptive nerve endings synapse in the spinal cord (substantia gelatinosa) or medulla (nucleus of the spinal tract of CN V).
2. Information passed to thalamus through the activation of secondary (projection) neurons.
Spinal Nucleus (C.N. V)
Referred Pain
Visceral Nociceptors
• Fibers usually run with autonomic fibers
• Large receptive fields
• Converge on neurons that receive somatic input
AMPA Receptor(-Amino-3-hydroxy-5-methylisoxazole-4-proprionic acid)
1. Natural agonist is glutamate2. Permeable to Na+ and K+, but not Ca2+ 3. Channel opening short (10 ms)
Glua
A
GluSP
CPN
AscendingCNS Pathways
1.Spino- and trigemino-thalamic tracts
2.Thalamus (sensory-discrimination)
3.Reticular/limbic systems (motivational-affective)
4.Cortex (cognitive-evaluative)
Gate Control Theory of Pain(Melzack and Wall, 1965)
A
A & C
DescendingCNS Pathways
Inhibition
Facilitation
Nx
PAIN
DRG DRG
Nx
ININ EXIN
+ +
PN
+- ++-
+
+
5-HT, NA(2)GABA, GLYENK, DNYEN, ACh
5-HT, NA(1)GLUT, SPACh (nic)
EN, GABA GLY, ENK
DNY ()
PN
ACh(nic)CCK
DNY (N)
SPGLUT
SPGLUT
Inhibition Facilitation
Endogenous Opioids& Stress-induced Analgesia
1.Enkephalins – dorsal horn2.Dynorphins –
hypothalamus, PAG, dorsal horn
3.-endorphins (involved in stress-induced analgesia) – hypothalamus
Hyperalgesia AllodyniaPain Response
StimulusIntensity
An increased responseto a normally painfulstimulus
An painful responseto a normally innocuousstimulus
“Pain Threshold”
Clinical Pain(Inflammatory or Post-surgical Pain)
Primary Hyperalgesia“Peripheral Sensitization”
Glutamate SP
Na+ ChannelsTTx-S/TTx-R
Heat VR1
H+ ASIC
ATP P2X2
PG’s
Bradykinin
NGF
Cytokines
VR1, Na+ channels.
A
B
A: Sensitization
B: Transcription
Secondary Hyperalgesia“Central Sensitization”
CNSPeripheryDRG/TG
• Injury and inflammatory response results in increased nociceptor activation
Injurysite
Afferent barrage leads to:• Increased excitability• Decreased inhibition
NMDA Receptor(N-methyl-D-aspartate)
• Natural agonist is glutamate; usually blocked by Mg2+ • Depolarization opens channel by removing block • Channel opening has a long duration (100 ms)
permitting summation of inputs (“wind-up”)
Ca++
Mg++Glu
SP
IP3
PN
AMPA
NMDA
Analgesics
The Pharmacological Approach
GlutamateSP
Na+ ChannelsTTx-S/TTx-R
VR1
ASIC
P2X2
PG’s
Opioids
Cytokines
Nx
PAIN
DRG DRG
Nx
ININ EXIN
+ +
PN
+- ++-
+
+
5-HT, NA(2)GABA, GLYENK, DNYEN, ACh
5-HT, NA(1)GLUT, SPACh (nic)
EN, GABA GLY, ENK
DNY ()
PN
ACh(nic)CCK
DNY (N)
SPGLUT
SPGLUT
Inhibition Facilitation
Peripheral Processes•Spontaneous activity•Sympathetic activity•Nociceptor sensitization
Central Processes•Central sensitization•Spinal reorganization•Cortical reorganization•Loss of inhibitory pathways
The Problem of Persistent Pain