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(8) Neurophysiology (Pain DORSAL HORN NEURON EXCITABILITY (Pain…
(8) Neurophysiology
Pain
DORSAL HORN NEURON EXCITABILITY
Directly activate nocieptor
(H-B-S-A-K-Glutamate)
K+ from damaged cells
ATP from damaged cells
Serotonin
from platelets
Bradykinin
(Precursor in plasma)
Histamine
from mast cells
CNS
: Glutamate / Substance P
PNS
: Brandykinin / Prostaglandin
Sensitize nociceptors
Decrease threshold for stimulus
(
PLS
-Tachykinin)
Prostaglandin from damaged cells
Leukotrienes from damaged cells
Substance P
from sensory neurons
Example of Tachykinin
Tachykini and CGRP contribute neurogenic inflammation
SP antagonist
ineffective against chronic pain
Vaniloid Receptor TRPV1
High threshold receptor
Chronic capsaicin densensitizes
Triggers
Capsaicin
H+
Heat
Pain Inhibitors
(SEED)
From interneuron
Serotonin
Endorphins
Enkephalins
Dynorphin
(
Opiates/Opium
mimic Enkephelins and Seratonin)
Prevent Ca2+ from entering cell and releasing NT
Prevent Adenylate Cyclase from working
K+ efflux
1) Reduce Glutamate (Secretion / Neutransmitter release from C Fibres)
2) Reduce Dorsal Horn neuron excitability
GABA, Glycine
CCK
NO
Gate Mechanism/Theory of Pain
Non-painful input closes gate for painful input
Mechanoreceptors
will activate inhibitory interneuron
Descending inhibitory fibres (eg.
Opiates/Opium
)
Types of Pain
Acute Pain
Known cause
Short duration
Resolution of underlying cause
Chronic Pain
Unknown cause
Persists after healing (>3mnths)
-Underlying cause pain and disorder
Neuropathic Pain
Pain becomes primary disease
Outlast tissue injury
Depedent on neuroplasticity
50% of nerve cells
1) Astrocytes
Immune cells
Isolation of BBB
Neurotrophic factors
2) Microglia
3) Ependyma
4) Oligodendrocytes
Myelin sheaths in brain
5) Schwann cells
Provide myelin sheaths in PNS
Neurotransmitters
Acetylcholine (Excitatory)
Glutamate (Excitatory / Inhibitory?)
NMDA
AMPA/kainate
Metabotropic receptor (mGluR)
Most common NS
GABA
and Glycine (Inhibitory)
Glycine facilitates excitatory with glutamate (NMDA)
Dopamine
Amine
Effects of Morphine:
Structurally similiar to Met-Enkephalin
Central
Analgesia
Euphoria
Somnlence --> Sedation
Depresses respiratory system
Nausea / Vomitting
Inhibit release of GnTRH, CRH
Peripheral
Gastro Motility Decrease
Release histamines (from mast cells)
Chronic Effects of Morphine
Tolerance
Imunouppressant
Heroine is an opiod too
Opiod Receptors
Meu
Most important
Delta
Respiratory depression
Reduced GI motility
Kappa
Sedation
Dysphoria
NOTE SIGMA ARE NOT OPIATE RECEPTORS
ORL Receptor
(an)algesic peptide
Forms of Learning
Perceptual (Visual)
Ventral Stream (What)
Dorsal Stream (Where)
Stimulus-Response
Motor
Relational (What and stimuli)
Types
of Synapses
Chemical
Excitatory
Depolarization
Promote A.P
Glutamate
Transported as Glutamine
Uptake
Surrounding glial cells
Neurons
Cholinergic
Delay
Ca2+ influx
Neurotransmittor Release
ACh broken down (Achesterase)
Choline reabsorbed by presynaptic & recycled
Inhibitory
Hyperpolarization
Suppress A.P
Glycine
Synthesized by
Precursor: Serine
Reabsorbed by
Glial cells
Post-synaptic
GABA
Synthesized from
Glutamate
Glutamic Acid Decarboxylase
Requires Pyridoxal Phosphate
Reabsorbed by
Postsynaptic
Glial Cells
Postsynaptic Receptors
Ligand-gated ion channels
(Direct)
Combined
Receptor
Channel
Aspartate
Glutamate
Acetylcholine
G-Protein-Coupled Receptors
(G-Protein)
Separated
Second Messengers
To open ion channel
Norepinephrine
GABA
Epinephrine
Histamine
Dopamine
Intra-cellular Enzymes
(Indirect)
Carbon Monoxide
Nitric Oxide
Electrical
Rare
Interlocking membrane proteins
Mechanically & Electrically linked (Gap Junction)
Ways to clear up cleft
Enzyme Deactivation
Diffuse out of cleft into blood
Reuptake / Glial
Divisions
CNS (Brain & Spinal Cord)
PNS (Neutral tissue outside CNS) *Not protected by (1) Bone - skull/spine (2) Blood-brain barrier
Afferent Division (Sensory from receptors)
Efferent Division (Motor to effectors)
Somatic (Conscious)
Autonomic (Unconscious) eg. BP, breathing
??
Long Term Potentiation
:
Long lasting
Increased efficacy
Chemical synpase
Hippocampus
Hebb's Rule (Repeated Firing)
Thicker cortex
More glial cells
More Ach
Step 1:
Glutamate
open ligand gate
AMPA receptor
>> Na influx
Step 2: Mg2+ unblocks
NMDA receptor
(Unblocked)
Step 3: Na/Ca2+ enters through
NMDA receptor
Step 4: Ca2+ influx causes
Increase Nitric Oxide activity
Increase Glutamate release at presynaptic cell (Nitric Oxide)
Translocation of more
AMPA
and
NMDA receptors
Growth factor produce other synapses
Long Term Depression
:
Increase until maximum efficacy
Difficult to encode new information
Selectively weaken synpases
How
Moderate levels of Ca activate phosphatase LTD
High levels of Ca activate kinase LTP
Synapses
Electrical Synapse (Rare)
Physically / Electrically
Gap junctions much shorter
Chemical Synapse (Common)
Gap junctions longer
Migraine
Theories
Vascular Theory
: Disregulation of blood flow
Neuro-vascular Theory
: Sterile Inflammation
Neuronal Theory
: Cortical Spreading of depolarization
What happens
Aura / Decrease in blood flow
Trigeminal
Nerve triggered
Releases
Substance P
Releases Calcitonin Gene Related Peptide (
CGRP
)
WBC aggregate and activate
Toll-like receptors
Misc
Blood Brain Barrier
Protect from
Pathogens
Toxins
Difference from normal
Fenestration smaller
Astrocyte
:
Maintenance
Structural Support
Pericyte
:
Permeability of BBB
Contractile Cells
Regulate capillary flow
Phagocytose cell debris
Glial cells
Tight Junctions: Have proteins which bind tightly to blood vessels
Alzhiemers & Schizophrenia