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Pharm & Dynamics of Anesthesia Agents > Analgesics, Pain Pathways and Pain Management > Flashcards

Analgesics, Pain Pathways and Pain Management Flashcards

1
Q

What is Nociception (Pain)?

A

An unpleasant sensory and emotional experience associated with actual or potential tissue damange

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2
Q

What are the three types of pain?

A

Nociceptive, inflammatory, and neuropathic

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3
Q

How is nociceptive pain activated?

A

Noxious stimuli
1) chemical
2) mechanical/ pressure
3) thermal (hot & cold)

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4
Q

What is involved with inflammatory pain?

A

Macrophages
Mast cells (histamine release)
Neutrophil granulocytes
Release of all types of cytokines/ chemicals like prostaglandins (which can cause altered capillary permeability)

The chemical mediators make the nociceptors more sensitive to pain and lower pain thresholds (can cause allodynia and hyperalgesia)

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5
Q

What type of pain is involved in acute to chronic pain?

A

Inflammatory pain

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6
Q

What type of medication works really well to relieve inflammatory pain?

A

NSAIDs

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7
Q

How is neuropathic pain activated?

A

Results from damage to the neuron itself

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8
Q

Is neuropathic pain easy or difficult to treat?

A

Extremely difficult, the most resistant to pain therapy!

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9
Q

What is the hallmark of neuropathic pain?

A

Allodynia**
Hyperalgesia **

Also:
Hypoaesthesia (numbness)
Paraesthesia (pins and needles)
Summation (pain sensitization is increased more each time)
Thermal hypersensitivities

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10
Q

What are the four steps of nociception?

A

Traduction
Transmission
Modulation
Perception

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11
Q

What occurs during transduction?

A

Nociceptors transform painful stimuli (chemical, pressure/ mechanical, thermal) into a signal or action potential (electrical stimulus)

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12
Q

Where are nociceptors mostly found?

A

Skin, joints, and muscles
On free nerve endings

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13
Q

Activation of nociceptors subsequently activates specific subtypes of ________ ion channels to general actional potentials called ________ and ________.

A

sodium

1) Nav 1.7
2) Nav 1.8

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14
Q

What nociceptor is stimulated by capsaicin?

A

TRPV1 (thermal nociceptor that can perceive noxious heat > 43C/ 110F)

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15
Q

Continuous stimulation of TRPV1 by capsaicin results in receptor _______________ and decrease in pain transmission.

A

Desensitization

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16
Q

What are the two main peripheral neurons/pain fibers involved in transduction?

A

A-delta fibers (myelinated)
C-fibers (unmyelinated)

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17
Q

Neurons (like the A-delta fibers) are categorized by what three characteristics?

A

Whether they are myelinated or not, their diameter size, and their propagation speed

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18
Q

What type of pain do A-delta fibers transmit?

A

Fast pain that is sharp and well-localized

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19
Q

What type of pain do C-fibers transmit?

A

Slow pain that is dull, stabby, achy, and poorly localized

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20
Q

Compare A-delta fibers and C-fibers &
where do they synpase?

A

A-delta: “first pain” is fast, sharp, well-localized pain; myelinated; fast conduction speed 5-30 m/s; larger diameter
-Synapse at Lamina 1 and V

C-fibers: “second pain” is slow, longer-lasting dull, aching, diffuse pain; unmyelinated; slow conduction speed < 2 m/s; smaller diameter
-Synapse at Lamina 1 and II (substantial gelatinosa)

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21
Q

Approximately ____% of C-fibers send collaterals to the descending pathways

A

80

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22
Q

What occurs during transmission?

A

The process of transferring pain information from the peripheral to the central nervous system and up to the brain along neuronal axons. The reflex arc is included.

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23
Q

During transmission, the pain signal is relayed through the ________________ while ascending up to the brain along the _________________ tract.

A

1) three-neuron afferent pain pathway
2) spinothalamic tract

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24
Q

What is another commonly used name for the spinothalamic tract?

A

The anterolateral system

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25
In the ascending, anterolateral system, what does the anterior portion sense?
Light touch & pressure
26
In the ascending, anterolateral system, what does the lateral portion sense?
Pain & temperature
27
During transmission, how does the first-order (presynaptic) neuron travel?
From periphery to dorsal horn (cell body in dorsal root ganglion)
28
During transmission, how does the second-order (post-synaptic) neuron travel?
From the dorsal horn to the thalamus (cell body in the dorsal horn). It crosses the contralateral side of the spinal cord and then ascends up to the brain via the spinothalamic tract.
29
During transmission, how does the third-order neuron travel?
From the thalamus to the cerebral (somatosensory) cortex (cell body in the thalamus). Located in the parietal lobe. This is the main place where we perceive pain.
30
What two excitatory neurotransmitters are released from the 1st order neuron to the 2nd order neuron in the dorsal horn?
1) Glutamate (the most common and the main endogenous ligand for NMDA receptors) 2) Substance P Also CGRP
31
Glutamate receptors are broken down into what two families?
1) Ionotropic (ion channels) - ex: NMDA receptor 2) Metabotropic (GPCRs)
32
What occurs during modulation?
The up or downregulation of pain signals throughout the spinal cord and brain. Ex: descending pathways (that meet with ascending pathways) inhibit pain signaling; gate-control theory
33
During modulation, the descending neuron stimulates a small neuron in the area called what?
Interneurons (opioid neurons)
34
During modulation, the interneurons release what?
Endogenous opioids such as endorphins, enkephalins & dynorphins *Also GABA
35
During modulation, what do interneurons do to the ascending pathway in the substantial gelatinosa?
When stimulated, they release endogenous opioids that control or inhibit pain signals from transmitting from 1st-order neurons to 2nd-order neurons in the ascending pathway = stopping the continuation of impulse up to the thalamus
36
The most important site of modulation is the ___________________ in the dorsal horn and is also called the Rexed Lamina II. It is where a lot of attenuation and modulation of pain occurs.
Substantia gelatinosa
37
Per Rhea, during modulation, what is the most important section of the descending inhibitory pain pathway?
Periaqueductal gray matter (PAG)
38
In the descending inhibitory pain pathway, what is the area in the brain that consists of grey matter that goes from the 3rd ventricle to the 4th ventricle?
Periaqueductal gray matter (PAG) *Is the beginning of the descending pain pathway
39
During modulation, pain is inhibited when the descending pain pathway releases _______, _________, and _______ _______ that prevent the release of excitatory neurotransmitters (Glutamate, Substance P) in the dorsal horn from being released from the 1st order neuron to the 2nd order neuron in the ascending pathway.
1) NE 2) Serotonin (5-HT) 3) Endogenous opioids (ex: endorphins, enkephalin) *from interneurons?? *Also GABA
40
During modulation, what part of the brainstem releases norepinephrine?
Locus coeruleus
41
During modulation, what 3 parts of the brainstem release serotonin?
1) Reticular formation 2) Rostral ventromedial medulla 3) Raphe nucleus magnus
42
During modulation, what part of the brainstem releases endogenous opioids (Enkephalin)?
Rostral ventromedial medulla
43
What is the main inhibitory neurotransmitter in the body?
GABA
44
What occurs during perception?
The awareness of pain associated with a specific area of the body. Pain processing is also influenced by environmental cues, cultural conditioning, and past experiences.
45
During perception, the processing of afferent pain signals mainly occurs where?
1) Cerebral (somatosensory) cortex* 2) Limbic system
46
What portion of the brain senses a lot of the sensitive nerve endings like the hands, lips, and face?
Homunculus
47
What area of the brain is responsible for our emotional response and behavior regulation?
Limbic system (cingulate cortex)
48
What area of the brain controls the ANS response (increased HR and BP)?
Hypothalamus
49
What area of the brain senses fear?
Amygdala
50
What two areas of the brain are responsible for learning, memory, and perception of pain?
The hippocampus and pre-frontal cortex
51
What area of the brain is responsible for our motivation and reward system?
Accumbuns & Ventral tegmental area
52
What area of the brain processes painful experiences and drives learning from pain?
Insula
53
What type of receptor is the opioid receptor?
G-protein coupled receptor
54
What happens during stimulation of an opioid G-Protein Coupled Receptor?
Nothing crosses the cell membrane. A ligand (opioid) gets bound to the outside of the cell, and on the inside of the cell, a series of pathways are stimulated. G-protein is activated Adenylate cyclase is inhibited Less intracellular concentration of cAMP (main 2nd messenger**) is produced Presynaptic: Ca channel conductance is decreased/ inhibited (neurotransmitters can not be released) Postsynaptic: Potassium channels are opened --> conductance increased --> outflux of potassium --> hyperpolarizes the neuron --> decreased RMP --> becomes more resistant to stimulation
55
What are the receptors in the endocannabinoid system?
1) CB1* - mostly CNS 2) CB2 - peripheral NS and immune cells
56
What are the endogenous ligands in the endocannabinoid system?
1) AEA: anandamide 2) 2-AG: 2-arachidonoyglyerol
57
The theory that describes that nonpainful stimuli can override painful stimuli (the rubbing effect) is called the _____ _______ _______?
Gate Control Theory Pain signals can be interrupted in the substantial gelitanosa of the spinal cord, which acts as a "gate."
58
What fibers are involved in the Gate Control Theory?
A-beta fibers (large-diameter, myelinated, deep pressure/ deep touch fibers). They are faster than A-delta fibers and C-fibers. Stops pain stimulus by inhibiting Ca channels and opening K channels.
59
What is the reflex arc?
Interneurons between the sensory neuron and motor neuron activate or deactivate certain muscle fibers. This coordinates the correct flexion and relaxation of muscles to WITHDRAW from painful stimuli.
60
What neurons are involved in the reflex arc?
A-alpha
61
Pain from internal organs and blood vessels is known as what?
Visceral pain Vague symptoms such as aching, squeezing and radiating pain
62
Pain that occurs when pain receptors in tissues (including the skin, muscles, skeleton, joints, and connective tissues) are activated is known as what?
Somatic or Cutaneous pain Also described as musculoskeletal pain
63
Visceral pain is transmitted up to the brain via which spinal tract?
Doral column tract **Somatic and cutaneous pain travel up the spinal cord via the spinothalamic tract
64
The visceral pain tract sometimes shares second-order neurons with somatic pain tracts and can cause what kind of pain?
Referred pain - the brain can get confused
65
If you have a spinal cord lesion on one side, how will the patient present?
They will have reduced pain sensation and temperature on the OPPOSITE side
66
The viscera responds more to what kind of sensations?
Ischemia, stretching, compression, and distension
67
In visceral pain, the dorsal column pathway does not synapse at the level of the spinal cord the way somatic and cutaneous fibers do. Where do the fibers synapse instead?
The medulla and it stays on the same side of the spinal cord.
68
What is the midline myelotomy?
Dissect fibers in the spinal cord for relief of severe visceral pain as palliative treatment for cancer patients.
69
What is analgesia?
Diminished or absence of pain without loss of consciousness
70
What is allodynia?
Pain from stimuli that normally does not provoke pain (ex: light brushing of skin, feather across skin)
71
What is hyperalgesia?
Exaggerated response to a usually painful stimuli
72
What is dysesthesia?
An "abnormal sensation"; is a general term for cutaneous symptoms without a primary cutaneous condition (pruritus, burning, tingling (pins, needles), stinging, crawling, hypoesthesia (numbness)
73
What is neuralgia?
Similar to dysesthesia but associated with a SPECIFIC condition (trigeminal neuralgia, post-herpetic neuralgia). Intense, intermittent pain, numbers & tingling along the nerve pathway.
74
What is neuropathy?
Damage or dysfunction to one or more nerves resulting in numbness, tingling, and muscle weakness, usually in hands and feet
75
What is paresthesia?
Tingling (pins, needles) or prickling sensations usually in hands or feet but can happen anywhere; COOL sensitivity
76
In the five-ring structure of opioids, what has the analgesic activity?
N-methylpiperidine moiety
77
Synthetic opioids only have ___ of the original 5 rings
2
78
Where are opioid receptors located in the central nervous system?
Supraspinal: medulla & midbrain Spinal: presynaptic opioid receptors
79
Where are the opioid receptors located in the peripheral locations?
GI, vasculature, lungs, heart, immune system, PNS
80
What are the 3 subtypes of opioid receptors?
Mu (1 & 2), Kappa, Delta
81
How do GPCR receptors work?
Inhibit cAMP & interact with ion channels Inhibit Ca channels, open K channels
82
Stimulation of mu (1&2) receptors produces what main 3 effects?
1) supraspinal analgesia 2) euphoria 3) respiratory depression (Mu 2**)
83
What symptoms are seen with stimulation of mu 1 receptors?
Supraspinal analgesia **Euphoria**, Sedation Prolactin release, catalepsy LOW abuse potential Miosis **Bradycardia** Hypothermia **Urinary retention** Pruritus
84
What symptoms are seen with stimulation of mu 2 receptors?
Spinal analgesia Respiratory depression** Physical dependence Constipation/ decreased peristalsis* N/V, increased biliary pressure Pruritus
85
What symptoms are seen with the stimulation of kappa receptors?
Supraspinal AND spinal analgesia **Dysphoria**, Sedation Hallucinations, delirium LOW abuse potential Miosis **Diuresis** - inhibition of vasopressin release **Anti-shivering**
86
What symptoms are seen with the stimulation of delta receptors?
Supraspinal AND spinal analgesia Respiratory depression* Physical dependence* Constipation (minimal) Urinary retention Pruritus
87
What endogenous ligand is associated with the mu receptor?
Endorphin
88
What endogenous ligand is associated with the kappa receptor?
Dynorphin
89
What endogenous ligand is associated with the delta receptor?
Enkephalin
90
What two opioids have active metabolites that could cause toxicity, especially in renal failure or elderly patients?
Morphine and meperidine
91
What areas of the brain are responsible for respiratory depression?
Pons and medulla
92
The euphoria and reward part of the brain is in the nucleus accumbens and the ventral tegmental area. How do opioid receptors cause euphoria?
Opioid receptors inhibit GABA receptors, which then increases dopamine receptors. It is an indirect way of increasing dopamine.
93
As set by the DEA, what schedule are most opioids?
II

Pharm & Dynamics of Anesthesia Agents (1 decks)

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