Pain Anesthesia Analgesia Flashcards
Pain
an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage
any pain of moderate or higher intensity is accompanied by (2)
anxiety and the urge to escape or terminate the feeling
Nociception
the unconscious activity induced by a harmful stimulus applied to sense receptors
Noxious Stimuli
harmful, poisonous or very unpleasant stimuli
Hyperalgesia
an exaggerated response to a noxious stimulus
Allodynia
a sensation of pain in response to a normally innocuous stimulus
example of Allodynia
the painful sensation from a warm shower when the skin is damaged by burns including sunburn
Sensitization
when intense, repeated, or prolonged stimuli are applied to damaged or inflamed tissues, the threshold for activating primary afferent nociceptors is lowered, and the frequency of firing is higher for all stimulus intensities
inflammatory mediators such as (4) contribute to this sensitization
bradykinin (BK),
nerve-growth factor (NGF),
some prostaglandins (PGs), and
leukotrienes (LTs)
(2) signify increased sensitivity of nociceptive afferent fibers and hence, nociception
hyperalgesia and allodynia
Analgesia
the inability or reduced ability to feel pain without loss of consciousness or other sensations
Analgesics
substances that reduce the ability to feel pain
examples of Analgesics (4)
non-steroidal anti-inflammatory drugs,
acetaminophen,
aspirin,
opioids
Anesthesia
insensitivity to pain
Anesthetics
substances that produce a general insensitivity to pain
General Anesthetics
depress the CNS to a sufficient degree to permit the performance of surgery and unpleasant procedures
examples of General Anesthetics (4)
isoflurane,
halothane,
nitrous oxide,
propofol
Local Anesthetics
substance that when in contact with a nerve trunk can
cause both sensory and motor paralysis in the area
innervated
examples of Local Anesthetics (3)
cocaine,
lidocaine,
bupivacaine
Mechanoreceptors (2)
mediate…
respond to…
mediate responses to touch and pressure
mechanical nociceptors respond to strong pressure (e.g. from a sharp object)
Thermoreceptors (2)
detect…
activated by…
detect the sensations of warmth and cold
thermal nociceptors are activated by skin temperatures above 45°C or by severe cold (<20°C)
Chemoreceptors (2)
stimulated by…
respond to…
stimulated by a change in the chemical composition of the local environment
chemically sensitive nociceptors respond to chemicals such as bradykinin, histamine, acidity, and environmental and chemical irritants, etc
Chemoreceptors are stimulated by a change in the chemical composition of the local environment, which include receptors for (2)
taste and smell as well as visceral receptors that are sensitive to changes in the plasma level of O2, pH, and osmolality
Receptors on Nociceptive Sensory Neurons
• variety of receptors on the endings of nociceptive sensory
nerves respond to (3)
noxious thermal, mechanical, or
chemical stimuli
Transient Receptor Potential (TRP) channels (2)
• TRPV1 receptors (the V refers to vanilloids)
• TRPA1 receptors (A, for ankyrin; protein that attaches
transmembrane receptors to internal cytoskeletal proteins)
TRPV1 receptors (the V refers to vanilloids) • activated by...
intense heat, acids, and chemicals such as
capsaicin (the active ingredient in hot peppers and an
example of a vanilloid)
TRPA1 receptors (A, for ankyrin; protein that attaches transmembrane receptors to internal cytoskeletal proteins) activated by...
activated by noxious mechanical, cold, and chemical stimuli
Acid-Sensing Ion Channel (ASIC) receptors
activated by…
may be…
pH changes within a physiologic range
may be the dominant receptors mediating acid-induced pain
Intermediate signaling molecules and receptors
• in addition to direct activation of receptors on nerve endings, some
nociceptive stimuli release intermediate molecules that then activate
receptors on the nerve ending
Adenosine Triphosphate (ATP)
• acts on purinergic receptors (e.g., P2X, an ionotropic receptor and P2Y, a
G-protein-coupled receptor)
Intermediate signaling molecules acting on G-protein-coupled
receptors (6)
- bradykinin
- histamine
- prostaglandins
- serotonin (5-hydroxytryptamine or 5HT)
- substance P
- Calcitonin Gene-Related Protein (CGRP)
Nerve Growth Factor
• acts on tyrosine receptor kinase A (TrkA) receptors
ATP signaling mechanism on ionotropic receptors is very similar to
acetylcholine (ACh)
Agonists (6)
bradykinin histamine prostaglandins serotonin (5-HT) substance P CGRP
Intermediate signaling molecules (8)
- adenosine triphosphate (ATP)
- bradykinin
- histamine
- prostaglandins
- serotonin (5-hydroxytryptamine or 5HT)
- substance P
- calcitonin gene-related protein (CGRP)
- nerve growth factor
All intermediate signaling molecules can produce — of nociceptive neurons
sensitization
All can produce sensitization of nociceptive neurons (2)
- immediate changes in neuronal responsiveness
* prolonged changes in neuronal responsiveness
• immediate changes in neuronal responsiveness
example:
• e.g. changes in membrane potential produced by altered calcium concentrations
• prolonged changes in neuronal responsiveness
example:
• e.g. produced by changes in gene expression
Primary Sensory Afferent Nerves • cell bodies located in the... • axon has two branches: • classified by their (3) • A-beta (Aβ)
dorsal root ganglia within the vertebral
foramina (or trigeminal ganglia for the head)
one projects centrally into the spinal cord
and the other projects peripherally to innervate tissues
diameter, degree of myelination, and conduction velocity
A-beta (Aβ) (4)
- largest diameter afferent fibers
- respond maximally to light touch and/or moving stimuli
- present primarily in nerves that innervate the skin
- In normal individuals, the activity of these fibers does not produce pain
A-delta (Aδ; myelinated) and C axons (unmyelinated) (3)
• both small diameter
• respond maximally only to intense (painful) stimuli
• produce the subjective experience of pain when they are electrically
stimulated
Pain Transmission Pathways
• fibers from nociceptors and thermoreceptors synapse on neurons
in the…
• or the — ganglion if coming from the head
dorsal horn of the spinal cord
trigeminal
Pain Transmission Pathways
axons from these dorsal horn neurons cross the midline and
ascend in the ventrolateral quadrant of the spinal cord, where
they form the
ventrolateral spinothalamic pathway
Pain Transmission Pathways
fibers within this tract synapse in the
ventral posterior lateral (VPL) nucleus
Pain Transmission Pathways
some dorsal horn neurons that receive nociceptive input synapse
in the (1) and then project to the centrolateral nucleus of the
—
reticular formation of the brainstem (spinoreticular pathway)
thalamus
Pain Transmission Pathways
pain activates the (6)
primary and secondary somatosensory cortex
the cingulate gyrus on the side opposite the stimulus
the amygdala,
frontal lobe,
insular cortex
Most nociceptors are — with small diameter axons (C-fibers, red). Their peripheral afferent innervates the — (dermis and/or epidermis)
and central process projects to
unmyelinated
skin
superficial laminae I and II of the dorsal horn
A-fiber nociceptors are — and usually have conduction velocities in the Aδ range (red). A-fiber nociceptors project to
myelinated
superficial laminae I and V
Ventrolateral spinothalamic tract mediates pain and temperature. These sensory fibers terminate in the dorsal horn and projections from there cross the midline and ascend in the ventrolateral quadrant of the spinal cord to the — and then to the — —- —
VPL
primary somatosensory cortex
Pain Transmission Pathways
• Somatosensory neurons are located in peripheral ganglia
(trigeminal and dorsal root ganglia) located alongside the (2)
spinal column and medulla
Pain Transmission Pathways
Afferent neurons project centrally to the — (Vc) and dorsal horn of the spinal cord and peripherally to the — and other organs
brainstem
skin
Pain Transmission Pathways
Vc,
trigeminal brainstem sensory subnucleus caudalis
Pain Transmission Pathways
•spinothalamic tract axons ascend to several regions of the
thalamus
Pain Transmission Pathways
tremendous divergence of the pain signal from these thalamic sites to several distinct areas of the cerebral cortex that subserve different aspects of the
pain experience
Pain Transmission Pathways
thalamic projections is to the
somatosensory cortex
Pain Transmission Pathways
thalamic projections is to the somatosensory cortex
• mediates the purely sensory aspects of (2)
pain (i.e. location, intensity, and quality)
Pain Transmission Pathways
thalamic neurons project to
cortical regions (e.g. frontal cortex, cingulate gyrus, insular cortex)
Pain Transmission Pathways
thalamic neurons project to cortical regions (e.g. frontal cortex,
cingulate gyrus, insular cortex)
• linked to — —-, subserve the affective or unpleasant emotional dimensions of pain
• exerts potent control of —
• therefore, fear is a constant companion of —
• injury or surgical lesions to areas of the frontal cortex activated by painful
stimuli can diminish the — impact of pain while largely preserving the individual’s ability to recognize noxious stimuli as painful
emotional responses
behavior
pain
emotional
Noxious stimuli activate the sensitive peripheral ending of
the primary afferent nociceptor by the process of transduction. The message is then transmitted over the peripheral nerve to the spinal cord, where it synapses with cells of origin of the major ascending pain pathway, the — tract. The message is relayed in the thalamus to the anterior cingulate (C), frontal insular (F), and somatosensory cortex (SS)
spinothalamic
Physiologic Basis of Pain Perception
Pain Transmission Pathways
• visceral sensation travels along the same central
pathways as — sensation in the spinothalamic tracts and thalamic radiations, and the cortical receiving areas for visceral sensation are —
with the somatic receiving areas
• this creates “— —” such as myocardial infarction
symptoms of pain radiating in left arm or left jaw
somatic
intermixed
referred pain
The basis for referred pain may be convergence of (2) fibers on the same second-order neurons in the dorsal horn of the spinal cord that project higher brain regions
somatic and visceral pain
Gate-Control Mechanism of Pain Modulation
• transmission in nociceptive pathways can be interrupted by actions within the dorsal horn of the spinal cord at the site of — — —
• (2) an injured area decreases the pain due to the injury
sensory afferent termination
rubbing or shaking
Gate-Control Mechanism of Pain Modulation
• — may be due to the simultaneous activation of innocuous cutaneous mechanoreceptors whose afferents emit collaterals that terminate in the dorsal horn
relief
Gate-Control Mechanism of Pain Modulation
• activity of these cutaneous mechanosensitive afferents may reduce the — of dorsal horn neurons to their input from nociceptive afferent terminals
responsiveness
Gate-Control Mechanism of Pain Modulation
• serves as the rationale behind the use of — — — for pain relief
• this method uses — to activate Aα and Aβ fibers near the
injury
transcutaneous electrical nerve stimulation (TENS)
electrodes
Endogenous Opioid Mechanism of Pain Modulation
• interneurons in the superficial regions of the dorsal horn contain
endogenous opioid peptides
• enkephalin and dynorphin
Endogenous Opioid Mechanism of Pain Modulation
• these interneurons terminate in the region of the dorsal horn where
— — terminate
nociceptive afferents
Endogenous Opioid Mechanism of Pain Modulation
• opioid receptors are located on the terminals of nociceptive fibers and on
dendrites of dorsal horn neurons, allowing for
both presynaptic and postsynaptic sites of actions for opioid
Endogenous Opioid Mechanism of Pain Modulation
opioid receptors are located on the terminals of nociceptive fibers and on
dendrites of dorsal horn neurons, allowing for both presynaptic and postsynaptic sites of actions for opioid:
• activation of the postsynaptic opioid receptors — the dorsal horn
interneuron by causing an increase in — —
• activation of the presynaptic opioid receptors leads to a decrease in — influx, resulting in a decrease in release of (2)
• together these actions reduce the duration of the — in the dorsal horn neuron
hyperpolarizes K+ conductance Ca2+ glutamate and substance P EPSP
Endogenous Opioid Mechanism of Pain Modulation
• activation of opioid receptors on dorsal root ganglia cell bodies also
contributes to reduced — from nociceptive afferents
transmission
— containing interneurons mediate their effects via opioid receptors on the terminals of nociceptive afferent fibers and on dendrites of dorsal horn neurons to exert both presynaptic and postsynaptic inhibition.
Enkephalin (ENK)
The action of an opioid (eg, morphine) within the DRG is to decrease —influx leading to a decrease in the duration of the invoked — —in the nociceptive neuron and a reduction in transmitter release from the nociceptive neuron onto a neuron in the dorsal horn.
Opioids also — the membrane of dorsal horn neuron by activation of a K+ conductance; opioids also decrease the amplitude of the — produced by stimulation of nociceptors.
Ca2+
action potential
hyperpolarize
ESPS
Opioid Analgesics (5)
- morphine
- codeine
- hydrocodone
- oxycodone
- fentanyl
mechanism of action of opiod analgesics (3)
- activate opioid receptors in neurons
- decrease intracellular calcium
- increase intracellular potassium
decrease intracellular calcium
• reduced — —
neurotransmitter secretion
increase intracellular potassium
• — cell making it refractory to depolarization
• reduced — — propogation
hyperpolarizes
action potential
Non-Opioid Analgesics (2)
- aspirin
* acetaminophen
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) (4)
- ibuprofen
- naproxen
- ketorolac
- celecoxib
Mechanism of Action (5)
- aspirin and NSAIDs
- inhibition of cyclooxygenase
- reduced production of prostaglandins
- reduced inflammatory-mediated pain signaling
- reduced sensitization of nociceptors
Local Anesthetics (6)
- articaine
- bupivacaine
- cocaine
- lidocaine
- mepivacaine
- prilocaine
Mechanism of Action of local anesthetics (3)
- blocks sodium channels
- reduces depolarization of neurons
- renders neuron refractory to further depolarizations
General Anesthetics (2)
- Inhalational Anesthetics
* Parenteral (Intravenous) Anesthetics
Inhalational Anesthetics (3)
- halothane
- isoflurane
- nitrous oxide
Parenteral (Intravenous) Anesthetics (4)
- propofol
- thiopental
- ketamine
- midazolam
Pharmacologic Basis of Pain Modulation
Mechanism of Action
• most general anesthetics increase the sensitivity of the
GABAa receptor to gamma-aminobutyric acid (GABA)
• enhancing inhibitory neurotransmission and depressing nervous system
activity
Pharmacologic Basis of Pain Modulation
Mechanism of Action
• inhalational anesthetics enhance the capacity of glycine to activate
glycine receptors
• which play an important role in inhibitory neurotransmission in the spinal
cord and brainstem
Pharmacologic Basis of Pain Modulation
Mechanism of Action
• halogenated inhalational anesthetics activate some
K+ channels known
• hyperpolarize neurons making them refractory to depolarization
Pharmacologic Basis of Pain Modulation
Mechanism of Action
• both inhalational and intravenous anesthetics have substantial
effects on — — and much smaller effects on — —- —
synaptic transmission
action potential generation or propagation
