E3 Nociception Flashcards
true or false
pain is subjective and conscious
true
what is not very accurate because of pain being subjective
the 1-10 scale
what is the fancy term for pain
algesia / nociception
What does anticipated pain do to the response
makes it worse
examples of pain without damage
emotional stress
phantom pain
what is nociception
an unpleasant sensory and emotional experience associated with actual or potential tissue damage
what is the precentral gyrus
before the central sulcus
motor
what is the postcentral gyrus
after the central sulcus
somatosensory / sensations
what controls / inhibits the ascending pathway
descending pathway
what sends the signal to the brain and is operational first before the descending pathway
ascending pathway
describe the ascending pathway
- immune cell / any cell is damaged
-releases cytokines (prostaglandin) - 1st order neuron through the dorsal root
-release substance P - 2nd order neuron decussates to spinothalamic tract
-goes up through the medulla, pons, midbrain, and ends in the thalamus - 3rd order neuron relays info to post central gyrus
what is PG generated from
arachidonic pathway
what is substance P
chemical that transmits signal
where does the scond order neuron terminate
thalamus
what is the thalamus
relay station
what part of the brain is the precentral gyrus
frontal
what part of the brain is the postcentral gyrus
parietal
true or false
sensation one the left side of the body goes up the left side and down the right
false
sensation is on opposite side of site of stimulation
what is a response to inflammation
PG
where does the nerve go in and out
goes in the dorsal root
goes out the ventral root
what makes up the brainstem
midbrain
pons
medulla
what is the perception of pain received in an area corresponding to
sensory/motor homunculus
what nuclei is norepinephrine
locus aeroli
what nuclei is serotonin
raphae magnus of medulla
describe the descending pathway
- 1st order neurons goes from periaquaductal gray matter of midbrain to nucleus raphae magnus of medulla
- meets second neuron that goes to the the same area of that the 1st and 2nd order neurons of the ascending pathway meet
- releases either serotonin or norepinephrine
-binds to presynaptic neuron and inhibits substance P by stimulating interneuron
-interneuron releases enkephalin (opioid)
where do the 1st and second motor neuron meet
substantia gelatinosa
where does the spinothalamic tract extend
goes from spine to thalamus
“decussates”
crosses over so the perception is on the opposite side of the brain
where are the intraneurons located
substantia gelatinosa
what does the interneuron do?
releases enkephalins (opioid)
-inhibits presynaptic neuron from releasing substance P
- inhibit post synaptic neuron from depolarizing
what does inhibiting the post synaptic neuron from depolarizing do
stops stimulus from continuing to thalamus
what is the biologically important function of pain
protective function
-normal response to injury or disease
what are manifestations of pain related to tissue injury
hyperalgesia
allodynia
hyperalgesia
exaggerated response to a noxious(harmful) stimulus
allodynia
perception of pain from normally innocuous(not harmful) stimuli
innocuous
not harmful
noxious
harmful
what are hyperalgesia and allodynia the result from
changes in peripheral/central nervous system referred to as peripheral or central sensitization
what can happen even after healing has taken place in some individuals
persistent (chronic) pain
what contributes to sensitization resulting in persistent (chronic) pain
genetic and environmental factors
what is chronic pain seen in a result from and examples
autoimmune disorders
lupus
rheumatoid arthritis
what do nociceptors signal and contribute to?
signal acute pain
contribute to persistent pathological pain disorders from previous injury or ongoing disease when chronically sensitized
characteristics of acute pain
begins suddenly, usually sharp
warning to disease/injury
disappears when underlying cause is treated
characteristics of subacute pain
lasts 6-12 weeks
improves with nonsurgical treatment
characteristics of pain
more difficult to treat
persists for months or years
may cause depression, anxiety, and sleep problem
what is chronic pain characterized by?
the abnormal state and function of the spinal cord neurons which become hyperactive
what does hyperactivity result from?
increased transmitter release
by spontaneously active primary afferent neurons
and
by increase responsiveness of postsynaptic receptors
- in part due to phosphorylation
How is a hyperexcitable state maintained?
by release of biologically active factors from activated glia
what are the activated glia normally that maintain a hyperexcitable state?
astrocytes and microglia
where does a hyperexcitable state occur?
dorsal horn
How is a hyperexcitable state aggravated?
by the loss of inhibitory interneurons involved in pain modulation
where is the substantia gelatinosa located?
dorsal horn of gray area
PTN
pain transmission neuron
PG
prostoglandins
EAA
exhibitory amino acids
what releases pro-inflammatory mediators
activated glia
what activated glia cells
Viruses and Bacteria
PTN
-NO
-PG
Primary Afferent
-Substance P
-EAA’s
-ATP
what does the activated glia then produce
pro inflammatory mediators
IL-1
TNF
ROS
NO
PG
EAA
ATP
what does the release of the substances form the activated glia enhance
enhance PTN excitability
enhance primary afferent, substance P and EAA release
when does the does nociceptive sensory systemreturn to normal function
as soon as healing takes place
when do many features of sensitization persist and manifest as chronic pain and hyperalgesia
system itself is injured, leading to chronic neuropathic pain
what is chronic pain accompanied according to imaging studies?
permanent structural alteration in specific brain areas that play a critical role in nociception
common types of pain
nociceptive
neuropathic
inflammatory
true or false
there are many ways to classify pain and classifications may overlap
true
nociceptive pain
normal response to noxious insult or injury of tissues such as skin, muscles, visceral organs, joints, tendons, or bones
examples of nociceptive pain
somatic
visceral
what is somatic nociceptive pain
musculoskeletal (joint pain, myofascial pain), cutaneous
often well localized
what is visceral nociceptive pain
hollow organs and smooth muscle
usually referred
neuropathic pain
pain initiated or caused by a primary lesion or disease in the somatosensory nervous system
where does neuropathic pain occur
anywhere on spinal cord up to brain
what do sensory abnormalities range from for neuropathic pain
deficits perceived as numbness to hypersensitivity (hyperalgesia and allodynia)
and
deficits perceived as paresthesias
what does paresthesias feel like
tingling, burning, prickling
(usually felt in appendages)
examples of neuropathic pain
diabetic neuropathy
postherpeutic neuralgia
spinal cord injury pain
phantom limb pain
post-stroke central pain
inflammatory pain
activation and sensitization of the nociceptive pain pathway by a variety of mediators released at a site of tissue inflammation
what mediators have been implicated as key players in inflammation ?
they do this by infiltrating what cells?
proionflammatory cytokine
leukocytes, vascular endothelial cells, or tissue resident mast cells
what are some examples of pro-inflammatory cytokines
IL‐1‐alpha
IL‐1‐beta
IL‐6
TNF‐alpha
chemokines
reactive oxygen species
vasoactive amines
lipids
ATP
acid
examples of inflammatory pain
appendicitis
rheumatoid arthritis
inflammatory bowel disease
herpes zoster (shingles)
true or false
pathological processes occur in isolation
false
never occur in isolation
characteristics of pathological processes
> 1 mechanism may be present
1 type of pain may be detected in a single patient
example of pathological processes as a clinical implication of pain
inflammatory mechanisms are involved in neuropathic pain
are all well-recognized pain disorders easily classifiable?
no
what are the treatments from pain disorders that are well recognized but not classified easy?
specific therapies are well known
examples of pain disorders that are well recognized but not classified easy
cancer pain
migraine
primary headaches
wide spread pain of the fibromyalgia type
how does phantom pain mirror therapy work
mirror neuron in our pre motor cortex
-fires when acts and observes by another
decreases pain by resolving conflict between motor intention proprioceptor and visual system
what fiber sensory afferent nerve fibers are involved in pain sensation
C-fiber
A-delta
c-fiber
non-myelinated (slow
aching pain later
mechanical
thermal
chemical
A-delta fiber
large, myelinated (fast)
sharp, immediate pain
mechanical
thermal
how does neuroplasticity relate to pain
strengthen or inhibit a pathway
-chronic continues to trigger/reinforce pathway
-so continues to change
can be desensitized
example of nerve damage
root canal
-nerve goes wild is what causes pain
enhanced pain from stimulus that does not usually produce that much
hyperalgesia
what type of pain is fibromyalgia
allodynia
-touch arm or certain clothing causes pain
refers to central pain sensitization following normally nonpainful, often repetitive, stimulation
allodynia
describe the simulus intensity and pain intensity graph
where does transduction happen
peripheral nerve (PNS)
where can transmission happen
central transmission
synaptic transmission
peripheral transmission
where are the A and C fibers located
dorsal root ganglion
what are the primary sensory neurons
EAA - excitatory amino acid
CGRP - calcitonin gene-related peptide
SP - substance P
Gal - galatin
NPY - neuropeptide Y
what is glutamate
excitatory amino acid (EAA)
what is galatin
neuropeptide g-couple receptor for K channels
hyperpolarizing effect
tranduction
conversion of stimulus into action potential
transmission
impulse travels to synapses in dorsal horn
secondary euron decussates
perception (where occurs)
cerebral cortex
modulation
facilitation or inhibition via descending efferent pathways/neurotransmitters
nociceptive nerve fiber Aα
efferent motor
fast, sharp pain
myelinated
nociceptive nerve fiber Aβ
afferent sensory
fast, sharp pain
myelinated
nociceptive nerve fiber δ (delta)
afferent sensory
5-30 m/s
fast, sharp pain
myelinated
nociceptive nerve fiber C
afferent sensory
0.5-2 m/s
slow, aching, throbbing pain
unmyelinated
what are the cells involve in tissue damage and inflammation and what do they specifically do?
mast cell & macrophage & platelets
-produce PAF (platelet activating factor)
-activates H1 (GCPR)
platlets
-produce bradykinins
-activates P2X2
damage (maybe platelets)
-activates A2 & ASIC
eosinophil & keratinocytes
-produce β endorphin (opioid)
-activate µ opioid
what modulators of tissue damage and inflammation are inhibitory
µ opioid
GIRK
M2
GABAa
what modulators of tissue damage and inflammation are GPCRs
SHT
H1 - histamine
EP - epinephrine
B1/2 - bradykinins 1&2
µ opioid
A2 - autoreceptor
M2
TRPV1 - transient receptor protein voltage
what modulators of tissue damage and inflammation are cytokine receptors (JAK kinase)
IL-1R
TRKA - capsalcin
what modulators of tissue damage and inflammation are ion channels
P2X2
ASIC - acid sensing ion channel
GIRK - g-protein inward rectifying K+
GABAa
what does A2 deal with
alpha 2
autoreceptor
dampening of signals
what does ASIC deal with
acid sensing ion channel
-activated when pH in body decreases
-injury = acidic environment
what does P2X2 deal with
ATP signaling
what does GIRK deal with
hyperpolarizing membrane
what does TRPV1 deal with
capsalcin
in peppers and icy hot
-rubbing injury / only used topically
open ion channels to respond to pain
is interneuron part or ascending or descending?
descending
gate theory of pain
pain reduced by activating a nonpainful sensation
rubbing can close the gate by inhibiting pain by going to the thalamus
-deep pressure activates pascinian corpuscles
what activates nociceptors
noxious stimuli (H+ / temp / etc. ) applied to endoorgans
what prostoglandins are released from injury (and from what)
released from damaged cells
PG E2
serotonin (5-HT)
nerve growth factor (NGF)
released from blood vessels
bradykinin (BK)
released from nociceptors
substance p (SP)
what do the prostoglandins etc. do once released from injury
activate nociceptors directly or sensitize them to subsequent stimuli
how do the nociceptors get sensitized to stimuli
parallel activation of intracellular kinases by GPCR and tyrosine kinase receptors
what are the primary nociceptive afferents what do they synapse with
C-fibers
A delta fibers
synapse to second motor neuron in substantia gelatinosa
what is released from the primary afferent terminals (A)
glutamate (Glu)
substance P
what does the release of glutamate do
activates glutamate receptors
- NMDA R
- AMPA R
- mGluRs
activates neurokinin receptors
- NK-1
located post synaptically on the spinal neurons
how are these synapses negatively modulated
by spinal inhibitory interneurons (I)
-employ enkephalins (Enk) or gamma-aminobutyric acid (GABA) as neurotransmitter
how does antinociception occur
activated noradrenergic or seotonergic systems activate inhibitory interneurons
what are depressive disorders from
exaggerated hyperalgesic effect
-level of neurotransmitters is lower / higher response
where is the gating of pain
substantia gelatinosa
what are the cannabinoid receptors in the endocannabinoid system
CB1 and CB2
GPCRs
what is the endocannabinoid system and receptors involved in
appetite, pain sensation, mood, memories
inflammatory pathways ? (potential)
what does CB1 do
reduce substance P being released
(presynaptic)
what do CB1 and CB2 mostly bind to?
anandamide (endogenous cannabinoid)
what does CB2 do?
suppresses reactive microglia behavior and central neuroinflammation
on glia (microglia)
antagonist
blocks
agonist
stimulates
what does alpha 2 do
stimulates the autoreceptor to reduce further neurotransmitter release
what acts on the brain
opioids
alpha2 agonists
centrally acting analgesics
NSAIDS
COX-2 inhibitors
what acts on the dorsal root
local anesthetics
opioids
alpha2 agonists
what acts on the peripheral nerve
local anesthetics
what acts on the peripheral nociceptors
local anesthetics
anti-inflammatory drugs
NSAIDS
COX-2 inhibitors
