3 - Acute Pain Flashcards
Allodynia
painful response to a normally non-painful stimuli
Hyperalgesia
exaggerated pain response to a normally painful stimuli
Neuronal Plasticity
Acute pain induced changes in the brain
What are nociceptors?
Free nerve endings located in the skin, muscle, bone
The nociceptice pathway is an ________ ascending system, made up of which two Nerve fiber types?
Afferent
A delta
Polymodal C
A delta fibers transmit _______
First pain
Polymodal C fibers transmit
Second Pain
What is the difference between first and second pain?
First pain is sharp and stinging
Second pain is dull/diffuse pain
What are the three primary afferent nerve fibers types?
A beta
A delta
C
What is the smallest afferent nerve fiber?
Largest?
Slowest?
Fastest?
C
A beta
C
A beta
A delta fibers carry signals from _______ receptors
C fibers carry signals from _______ receptors
specialized sensory
Free nerve ending
What are first order and second order neurons?
1st order neurons are located in the specialized sensors and carry impulses to the dorsal horn where they synapse with second order neurons on the same level
OR
ascend via lissauer’s tract to the second order neurons above
Where are third order neurons located?
in the reticular formation
periaqueductal gray
thalamus
What is the function of the efferent modulating pathway?
It sends impulses from the brain down to the level of the dorsal horn and modulates the response transmitted by afferent nerve fibers
What are the four elements of pain processing?
- Transduction
- Transmission
- Modulation
- Perception
Define:
Transduction
Transmission
Transduction is when a stimuli sparks an action potential in receptors
Transmission is when they action potential is passed to the first, second and third order neurons
Identify the location of cell bodies for the following:
First order neurons
Second order neurons
Third order neurons
Dorsal root
Dorsal Horn
Thalamus
Modulation involves altering ________
afferent neural transmission along the pain pathway
What is the most common site of modulation?
Dorsal Horn
List two types of spianl inhibitory modulation:
- Release inhibitory neurotransmitters (GABA)
- activation of efferent pathway (norepinephrine, serotonin 5HT, Enkephalin endorphin)
Traditional analgesic therapies targeted only _________
pain perception
IV fentanyl will affect which element of the pain pathway?
Perception
Ketamine will affect which element of the pain pathway?
Modulation
NMDA receptor antagonist
Duramorph will affect which element of the pain pathway?
Modulation
A peripheral nerve block will affect which element of the pain pathway?
Transmission
A bupivicaine epidural will affect which element of the pain pathway?
Transmission
How is preventive analgesia accomplished?
preventing NMDA receptor activation in the dorsal horn
(associated with windup, facilitation, central sensitization expansion of receptive fields, and long-term potentiation, all of which can lead to a chronic pain state)
What are the three necessities for preventive analgesia to be effective?
- Must block ALL nocicpetive stimulation during surgery
- Must include the entire surgical field
- Duration must span both operative and postoperative periods
What causes neuropathic pain?
Damage to the nerves themselves
may be delayed and may not be dermatomal
What are the top five surgeries that are known to cause neuropathic pain?
- Limb amuptation
- breast surgery
- gallbladder surgery
- thoracic
- inguinal repair
Codeine and tramadol are examples of ________
prodrugs
Require metabolism by CYP2d6 to be activated
Three primary mechanisms of opiods at the level of the spinal cord:
(1) inhibition of calcium influx presynaptically, resulting in inhibition of depolarization of the cell membrane and decreased release of neurotransmitters and neuropeptides into the synaptic cleft
(2) enhanced potassium efflux from the cell postsynaptically, resulting in hyperpolarization of the cell and a decrease in pain transmission
(3) activation of a descending inhibitory pain circuit via inhibition of GABAergic transmission in the brainstem
What are the signs of inadequate dosing of opiods during surgery?
dilated pupils
increased HR and BP
increased RR
multimodal perineural analgesia is a cocktail of:
buprenorphine
bupivicaine
clonidine
dexmedetomidine
NSAIDs inhibit:
Cyclooxygenase (COX) enzymes
Why do NSAIDs shred your stomach?
Cox 1 is responsible for gastric protection and hemostasis
Cox 2 produces prostaglandins which lead to pain and inflammation
If you inhibit cox to inhibit COX2, you also end up inhibiting COX1
Why do NSAIDS and COX2 inhibitors cause fluid retention and hypertension?
Prostaglandins play a crucial role in renal function because they are potent local and humoral vasodilators
If you block them, you get constriction in the afferent arterioles of the glomerulus, leading to fluid retention and high blood pressure
How do inhaled volatiles effect neuromuscular function? (2)
- directly relax skeletal muscle (dose dependent)
- Potentiate the action of NMBA agents
How is uterine muscle tone effected by inhaled anesthetics?
Decreased uterine tone
When administering volatile anesthetics for an emergent c-section under general, what can be done to prevent uterine atony?
Use 05-0.75 MAC of gas in combination with N2O
Experienced nurses tend to ________ pain
Inexperienced nurses tend to ________ pain
underestimate
overestimate
What is glutamate?
Major excitatory neurotransmitter released from A delta and C nerve fibers
Fast, sharp pain
What is nociceptive pain?
caused by the stimulation of specific nociceptors
What are the two types of nociceptive pain?
Somatic (identifiable locus, sharp, stinging) - i.e. first pain
Visceral (dull, cramping, diffuse - i.e. second pain)
Visceral pain is often associated with ________
distention of an organ capsule
obstruction of a hollow viscus
Visceral pain is often accompanied by which autonomic reflexes?
Nausea
vomiting
diarrhea
Non-nociceptive pain is categorized as _______
neuropathic
What causes inflammatory pain?
multiple mediators released from the site of inflammation cause sensitization of the nociceptive pathway
Pain transmitted by Polymodal C fibers is often described as _________
burning, throbbing, dull, aching
What is Substance P?
released from C fibers
Involved in slow, chronic pain
What is histamine?
Released from mast cells, basophils, and plateletes via substance P
Produces edema and vasodilation
Potentiates bradykinin pain
What is serotonin?
Amine stored and released from platelets after tissue injury
Algesic effect on peripheral nociceptors
potentiates bradykinin pain
What are prostaglandins?
metabolite synthesized from COX-1 and COX-2
Associated with chronic pain
Sensitizes peripheral nociceptors, causing hyperalgesia
What are cytokines?
Mediators released by tissue damage and inflammation
lead to increased production of prostaglandin, causing excited and sensitized nociceptive fibers
What is CGRP?
Calcitonin gene-related peptide
released from C fibers
causes sensitization of sensory nerves
What happens when chemical mediators and neurotransmitters stimulate peripheral nociceptors?
sodium channels open
nerve is depolarized
action potential develops into a pain impuse
What are the two types of second order neurons?
Nociceptive (received from A delta and C fibers)
Wide-dynamic Range (WDR) that receive from A delta, C, and A beta
What is the other name for serotonin?
5HT
Where do second order neurons synapse with third order neurons?
What happens once they do?
In the thalamus
Thalamus sends projection of pain to the cerebral cortex, the hypothalamus, and anterior cingulate
The descending efferent modulatory pathways are considered the body’s __________
pain control system
What are the excitatory neurotransmitters?
Substance P
Gultamate
What receptor does Glutamate bind to in order to cause excitation?
NMDA receptor
This is how ketamine works
What are the inhibitory neurotransmitters?
Glycine
GABA
Enkephalin
Serotonin
Norepinephrine
Norepinephrine is an inhibitory neurotransmitter. How does this relate to regional anesthesia?
This is why A2 agonists cause analgesia. They bind to the Alpha 2 receptors, just like norepinephrine would, and inhibit pain transmission
What are four predictors of post op pain?
Presence of preop pain
patient fear regarding the outcome of their surgery
patients who catastrophize pain
if post op pain is expected
All NSAIDs possess what properties?
anti-inflammatory
anti-pyretic
analgesic
Why does inhibiting COX decrease pain and inflammation?
By inhibiting COX, they prevent conversion of arachindonic acid to prostaglandins
Prostaglandins are responsible for sensitizing and ampliying peripheral nociceptors to the inflammatory mediators
How do prostaglandins influence pain?
They do not directly cause pain
they contribute to hyperalgesia by increasing the sensitivity of nociceptors to inflammatory mediators
30mg IM ketorolac is equivalent to how much morphine?
12mg IM
When should ketorolac not be given?
Beyond five days
coagulopathy, renal failure, active ulcers, GI bleed, asthma
Tylenol is not a true NSAID. So why does it decrease pain?
Reduces prostaglandin synthesis somehow
minimal anti-inflammatory effects
How do opioids inhibit pain?
bind to and activate G-protein coupled receptors (GPCR) both peripherally and in the CNS
This inhibits calcium channels and decreases release of excitatory neurotransmitters (like substance P) presynaptically
It also hyperpolarizes the post-synaptic junction and inhibits response to excitatory neurotransmission
What does NMDA stand for?
N-Methyl-D-Aspartate
What is the resting state of the NMDA receptor?
Closed
plugged by magnesium
What causes the NMDA receptor to open?
What happens once it does?
Glutamate
binding causes an influx of calcium, resulting in second messengers
Second messengers causes hyperexcitability of the NMDA receptors, which amps up algesia
Hence ketamine’s role in preventing “wind-up”
Clonidine and Precedex are _______agonists
A2 adrenergic
What do clonidine and precedex bind with?
GCPA A2 receptors in dorsal horn and peripherally
activation results in inhibition of cAMP 2nd messenger
What happens when A2 agonists bind with GPCA?
decreased cAMP
presynaptic: inhibits voltage gated Ca channels
postsynaptic: activates potassium channels to hyperpolarize
Which is more selectively an A2 adrenergic agonist, precedex or clonidine?
Precedex
What would be the effect of A1 adrenergic agonist action?
sedation, hypotension, bradycardia
How do local anesthetics block transmission?
block sodium channels in afferent and efferent neuronal membranes
Which anticonvulsants are often used to treat pain?
gabapentin and lyrica
Which antidepressants help with pain?
SNRIs
duloxetine, venlafaxine
What is a unique side effect of methadone that isn’t seen with other opiods?
QT prolongation
Define opioid tolerance
a change in the dose-response relationship
What is opioid induced hyperalgesia?
escalating doses of opioids result in increasing hyperalgesia and allodynia
What is the difference between opioid addiction and pseudoaddiction?
addiction is pathologically pursuing reward/relief by substance use (cravings, obsessive thoughts, compulsive use)
Pseudoaddiction in drug seeking behavior that is actually due to inadequate analgesia. when they receive higher doses, they no longer demonstrate drug seeking behavior
Should you leave or remove an implanted intrathecal or epidural opioid infusion system preop?
It should stay and continue perioperatively
In neonates, how well developed is the nociceptive pathway?
Descending pathway?
Well
Poorly
Leads to increased pain perception and stress response
85% of ascending C fibers terminate in the:
Reticular Formation
