Cathy Carlson, PhD, RN Northern Illinois University€¦ · Cathy Carlson, PhD, RN Northern...
Transcript of Cathy Carlson, PhD, RN Northern Illinois University€¦ · Cathy Carlson, PhD, RN Northern...
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Receptors and Neurotransmitters: It Sounds
Greek to MeCathy Carlson, PhD, RN
Northern Illinois University
Agenda
• We will be going through this lecture on basic pain physiology using analogies, mnemonics, cartoons, rhymes, songs, games, and visualizations to: – learn and – learn to teach pain physiology
What We Know About Pain
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Anatomy of a Neuron
Structural Classes of Neurons
Unipolar Sensory Neurons and Ganglia
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Pain & Sensory Receptors
Primary Afferent Sensory Nerve Fibers
• A-alpha (Aα)– Carry information related
to proprioception (muscle sense)
• A-beta (A-β)– Carry information related
to touch• A-delta(A-δ)
– Carry information related to pain and temperature
• C-nerve fibers – Carry information related
to pain, temperature, and itch
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1. Transduction - noxious stimuli are converted to electrical signals in sensory nerve endings.
2. Transmission - neural events which relay the information from the periphery to the cortex.
3. Modulation - the nervous system can selectively inhibit the transmission of pain signals.
4. Perception - subjective interpretation by the cortex of the noxious stimulus.
a. Sensory component (intensity, location)
b. Affective component (psychological)
Neural Steps in the Processing of Pain Signals
Transduction
Transduction
• Begins in periphery• All cellular damage caused by thermal,
mechanical, or chemical stimuli result in the release of pain producing excitatory mediators
• Mediators surround the pain fibers in the extracellular fluid, spreading the pain message through excitation (depolarization) of the free nerve endings (nociceptors) of the pain fibers – Also causes the inflammatory response
• This is called nociception• “Nocire” means to suffer
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Peripheral Excitatory Mediators
Substance Receptor Mechanism
Substance P(SP)
NK1 neuronal excitability, edema
Prostaglandin(PG)
? Sensitize nociceptors, inflammation, edema
Bradykinin B2 (normal)
B1 (inflammation)
Sensitize nociceptors PG production
Histamine H1 C-fiber activation, edema,vasodilation
Serotonin 5-HT3 C-fiber activation, release SP
Norepinephrine(NE)
1Sensitize nociceptorsActivate nociceptors
Threshold
Threshold
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Depolarization
• Sodium/potassium pump polarizes neuron – At resting state:
• K+ intracellular• Na++ Extracellular• More negative
intracellular
• Stimulus begins wave of depolarization as Na++ ion channels open and Na++ rushes in
• Wave of repolarization follows close behind
Opening of the Ion Channels• Touch-pressure:
– Mechanical tension opens ion channels• Rapidly adapting mechanoreceptors: vibration, touch, mov
ement• Slowly adapting mechanoreceptors: pressure
• Sense of posture and movement:– Muscle stretch opens ion channels
• Muscle spindle stretch receptor:– Responsible for the senses of posture and kinesthesia (sense
of movement at a joint)– Sense organs of balance: vision, vestibular organs, muscle
spindles
• Temperature: Heat and cold– Changes in temperature opens ion channels
• Pain:– Tissue damage release chemical mediators
that open ion channels
Transmission
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Transmission
• The transmission process occurs in three stages
• The pain impulse is transmitted:1. From the site of transduction
along the peripheral afferent neuron (first order neuron) to the dorsal horn in the spinal cord
2. From the spinal cord to the brain stem (second order neuron)
3. Through connections between the thalamus, cortex and higher levels of the brain (third order neuron)
Transmission
Characteristics and Functions of C fibers and A-δ Fibers
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Firstpain Second
pain
Time
Painintensity
C‐fiber
A fiber
A δ and C Fiber Pain
Transmission
• C fibers and A-δ fibers terminate in the dorsal horn of the spinal cord
• A synapse exists• A synapse contains three elements:
1. Presynaptic neurona. Presynaptic terminal
2. Synaptic cleft3. Postsynaptic neuron
a. Receptive membrane
• For the action potential to be transmitted across the synaptic cleft to the postsynaptic neuron, excitatory neurotransmitters are released, which bind to specific receptors on the postsynaptic neuron
Release and Reuptake of Neurotransmitters
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Major Excitatory Neurotransmitters of Pain in Spinal Cord
Synapse in the Dorsal Horn of Spinal Cord
Central Nervous System Ascending Pathways
• Spinothalamic Tract–Two subdivisions:• Neospinothalamic
tract (lateral spinothalamic tract)–Acute pain
• PaleospinothalamicTract (anterior spinothalamic tract)–Dull/burning pain
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Second Order Neurons in Spinal Cord
• Types–Wide Dynamic range
• Receive impulses from A-beta, A-delta, & C
– Nociceptive specific• Receive impulses from A-delta & C
– Interneurons• May be inhibitory
or excitatory
To Brain To Brain
-+
Dorsal HornLamina V
Wide Dynamic Range Neuron
Dorsal HornLamina I, V
Nociceptive Specific Neuron
A ACPolymodal
CPolymodalA
Second Order Cells in the Spinal Dorsal Horn
Wide Dynamic Range (WDR)
Nociception Pathways
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Perception
Perception• Point at which person is aware of pain
• Fast pain stimuli are transmitted up spinal cord to via the neospinothalamictract with some fibers to the thalamus and the majority of fibers to the somatosensory cortex– Identifies location & intensity of pain
Perception• Slow pain stimuli are transmitted up
spinal cord to via the palespinothalamic tract to the midbrain and thalamus limbic system
• Limbic system-controls emotion, anxiety, & emotional reaction to pain
• Responses to pain can be physiological and behavioral
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Modulation
Modulation of Pain
• Involves changing or inhibiting transmission of pain impulses in the spinal cord.
• Multiple, complex pathways involved in the modulation of pain
• Increases the transmission of pain impulses (excitatory) or decreases transmission (inhibition)
Modulation of Pain at the Spinal Cord Level
• Gate Control Theory of Pain– Pain impulses can be regulated or even
blocked by “gating” mechanism along CNS
– Theory suggests that pain impulses pass when gate is open and blocked when gate is closed
– Closing the gate is basis for pain relief interventions
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Gate Control Theory of Pain, Cont.
• Involves the addition of mechanoreceptors (A-β neurons), which releases inhibiting neurotransmitter (Serotonin)
• If dominant input is from A-β fibers, gating mechanism will close, pain reduced, due to release of Serotonin
• If dominant input from A-δ fiber, gate will be open and pain perceived
• Release of endorphins also close gate
Descending Modulatory Pain Pathways (DMPP)
• Transmit impulses from the brain (corticospinal tract in the cortex) to the spinal cord (lamina)– Periaquaductal Gray Area
(PGA) – releases enkephalins– Nucleus Raphe Magnus (NRM)
– releases serotonin– The release of these
neurotransmitters inhibit ascending neurons
• Stimulation of the PGA in the midbrain & NRM in the pons & medulla causes analgesia.
Descending Modulatory Pain Pathways (DMPP)
• Afferent stimulation of periaqueductal gray (PAG) area stimulates efferent neurons– Periaquaductal Gray Area
(PGA) – releases enkephalinsand secretes serotonin
– Rostral pons secretes norepinephrine
– Nucleus Raphe Magnus (NRM) – releases serotonin
• Efferent neurons synapse in medulla
• Impulse travels to dorsal horn to block afferent sensory fibers
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Inhibitory Neurotransmitters of Pain
• Inhibitory neurotransmitters involved with the modulation of pain include:1. Endogenous opioids • Endorphins, enkephalins, dynorphins, and
endormorphins2. Gamma-aminobutyric acid (GABA)
• Widespread in brain and spinal cord• Inhibitory GABA receptors on WDR
neurons inhibit excitatory neurotransmitter release3. Neurotensin
• Highest levels in hypothalamus, amygdala, and nucleus accumbens
• Causes analgesia and is also involved in regulation of dopamine pathways
4. Acetylcholine• Increased release of spinal acetylcholine is
associated with an elevated pain threshold
Amygdala
Inhibitory Neurotransmitters of Pain
5. Oxytocin• Released by receptors in the PGA• Believed to play an antinociceptive role• Binds to μ and κ opioid receptors
6. Norepinephrine• Different effects in different parts of body• In descending pathways causes inhibition of transmitter release
from peripheral afferent neuron7. Serotonin (5-HT)
• Inhibits pain in pons and medulla• Transmitter in descending inhibitory pathways• Inhibits substance P transmission in
dorsal horn (mechanism uncertain)8. Dopamine
• Inhibits processing of pain in multiple levels of the central nervous system including the spinal cord, periaqueductal gray (PAG), thalamus, basal ganglia, insular cortex, and cingulate cortex
PGA
Cingulate Cortex
Endogenous Opioids• Endorphin receptors are found in periphery, ascending, and descending
pathways
• 4 Types1. Endorphins
• Located in hypothalamus and pituitary• Bind to both μ and δ receptors with comparable affinity• Produce a sense of exhilaration, or “high”
2. Enkephalins• Located in neurons of brain, spinal cord• Bind with the δ receptor• Found concentrated in the hypothalamus, the PAG matter, the nucleus raphe magnus of the
medulla, and the dorsal horns of the spine
3. Dynorphins• Bind with the κ receptor• Located in the hypothalamus, the brainstem, PAG, rostral ventromedial medulla (PAG-RVM)
system, and the spine• Most powerful
4. Endomorphins• Located in the brain and the spinal cord and PNS • Show the highest affinity and selectivity for the μ receptor• Thought to assist in adaptation to pain and stress and enhancement of reward perceptions
• Release of endorphins can raise an individual’s pain threshold
• Release is increased by– Stress, excessive physical exertion, acupuncture, intercourse, and other factors
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Opioid Receptors• Important opioid
receptors:– mu (), kappa (),
delta ()– Activation of opioid
receptors by endogenous opioids inhibits the release of excitatory neurotransmitters such as substance P in the brain, spinal cord, and peripheral nervous system
Opioid Receptors
Questions?