Section 3 Pain Flashcards
The detection and localization of a stimulated pain receptor:
nociception
The emotional (affective) and arousal aspects of such stimulation:
pain
T or F? Pain and temperature are transmitted along different pathways.
F. same pathway
T or F? All thermoreeptors are specialized for non-noxious temperature ranges.
F. Some (same for noxious)
Temp range bw 50’ and 140’ stimulates:
TRPA1, M8, V4, V3, V3, TRPV1, TRPV2 (low temp to high temp)
At what temp do thermoceptors plateau out?
after 140’
Fire at a high rate of increase at the 45’ C range:
TRPV1
Fire at a high rate of increase at 50’ C:
TRPV2
Fire at a higher rate at decreasing temperatures:
TRPV4, TRPM8, TRPA1
How do thermoceptors respond to increasing temps?
by changing their conformation
TRPM8:
increases firing as things get cool and activated by menthol
Why is menthol cool?
transmitted via TRPM8, temps under 25 ‘C
Which are activated by capsaicin:
TRPV1 fibers, active as it gets hotter normaly, 45’ C
Medical tx using capsaicin:
arthritis ointment, gradually hyperactivates nociceptor axons, depleting its NT (substance P) and blasts them out, making nonfxnal, TRPV1
What is the NT for arthritis?
Substance P
A-delta nocioceptors:
thinly-my, fast conducting, fast pain (sharp, prickling, localized)
C nocioeptors:
unmy, slower conducting, slow pain (diffuse, burning)
A nocipceptor that responds to all types of stimuli:
polymodal (therm, mechanical, heat and cold)
Localized response to stepping on a tack, and then diffuse later:
differentiation comes bc we have 2 types of fibers that transmit at different rates
What activates nocioceptors?
Heat, cold, mechanical, chemical
T or F? Some nociceptors respond to only one type of stimulus.
T
What gives rise to the inflammatory soup?
Damage cells leak contents which activates the nocio endings giving rise to the inflammatory soup
Contents of the inflammatory soup:
ATP, serotonin (5-HT), histamine, bradykinin, H+, prostaglandins
Reduce pain by taking:
an aspirin, reduces prostaglandin production
What does tissue damage lead to?
the release of substances that activate nociceptors
What is 5-HT?
Serotonin
Both aspirin and IB profin block:
COX-2
Which is more selective, aspirin or Ibuprofen?
Ibuprofin
Pwy from tissue damage to pain:
Cut, arachidonic acid, COX-2, prostaglandins, pain
Ibuprofin only blocks:
COX-2
Aspirin blocks:
both Cox-1 and Cox-2
Blocking Cox-1 is associated with?
GI symptoms
Selectively blocks pain and not other sensations:
Analgesic
Anesthetics block:
non-selectively, not just pain
Lidocaine blocks:
voltage gated Na channels, blocks all n. conduction, unable to move nearby mm. as well)
Name an analgesic.
Aspirin
T or F? APs can’t invade non-stimulated nociceptor branches.
F. they can
What NT increases activation of nearby nocioceptors?
Histamine
How can pain lead to edema and more pain?
APs invade non-stimulated branches, nociceptor endings release Sub P and CGRP (calcitonin Gene-Related Peptide), Sub P activates mast cells, macros, and neutrophils, which release pain producing substances. CGRP and SubP cause vasoldilation, plasma leaks out, including bradykinin, edema and more pain
Increased sensitivity to painful stimuli:
hyperalgesia (prone to heightened pain if area has already been hurt (soup and other aspects of CNS)
Pain due to a stimulus that deos not normally provoke pain:
allodynia
Painful, inflammatory condition usually caused by carious bacteria penetrating dentin:
pulpitis
Early events in inflammatory pain:
vasodilation, inc interstitial fluid P, pain
Early symptoms of pulpits:
hypersensitivity of tooth (cold, hot evoke a stab of short lasting pain)
Type of receptors peripheral neurons have:
Opioid
Major source of peripheral opioids:
Immune cells
Endorphins:
bind receptors in the brain
“endorphin” stands for:
Endogenous morphine
Types of endorphins:
enkephalins, endo(mo?)rphins, dynorphins
Endogenous opioid receptors:
delta-OR, kappa-OR, mu-OR, nociceptin/orphanin FQ peptide receptor
Synthetic ligands for ORs:
codeine, oxycodone, morphine, heroin, methadone, usually similar to opium
Effects of peripheral opioid receptors:
Change levels of 2nd msgs (i.e. cAMP), reduce Ca channel opening, cell depolarizes, Sub P, CGRP, and other nasty things leak out. Less Na channel opening, leads to less pain conduction to CNS
What differentiates pain fibers from others?
Na channel type (1.8 and 1.9 for damage sensing?) for AP transmission to s.c. (sometimes overexpressed making the axon hyperexcitable)
What may develop after traumatic damage to a peripheral nerve?
causalgia, improper n. regeneration, excess Na channels, easier to generate APs even wo pain stimulus
T or F? Strong analgesics can tx causalgia.
T. ish. Sometimes not enough
Hypothesized mechanism of causalgia:
upregulation of Na channels
How does an Inflamed nerve differ from a normal nerve?
less my, more voltage sensitive Na channels, easier to get APs when they should be firing, cross-talk, new kinds of Na channels can appear
What starts to get expressed in pulpits?
New kinds of Na channels on my polymodal A-delta fibers
What happens to my polymodal A-delta fibers if they start to loose their my?
cross-talk
What controls how much pain info reaches consciousness?
Descending projections
What can lead to hypersensitivity to pain or the damping down of pain?
Local changes in the s.c.
Where does modulation of pain transmission take place?
s.c.
Why do you instinctively rub a site of pain?
Activation of touch fibers activates interneurons that inhibit pain, this reduces the amount of pain info going to higher levels
What determines how much pain gets up to consciousness?
interneurons
What can activate the inhibitory neurons that can damp pain?
touch and pressure
T or F? Endorphins work in both the CNS and PNS.
T
The gate control theory of pain:
Stimulate pain fiber, depolarize terminal, Ca enters, glutamate and Sub P released, excite projection neuron
Presynaptic mech to reduce pain transmission:
release endorphins that shut down voltage gated Ca channels. Little transmitter coming out of the pain fiber, less transission of pain
Postsynaptic mech to reduce pain transmission:
increase K channel activity via binding of Sub P to receptor, K channels open, K leaves, hyperpolarizing cell, less pain transmission (lower endorphin firing rate)
What does morphine mimic?
effects of dorsal horn inhibitory interneurons
What are the key to understanding opiate analgesia?
opioid interneurons
Disadvantage to (dorsal horn inhibitiory interneurons?)
opioid receps are all over the brain that are not involved w pain
Opioid overdose leads to:
depression of breathing
What happens with prolonged use of opioids?
Brain desensitized, higher and higher doses required
TENS stands for:
Transcutaneous Electrical Nerve Stimulation
To relieve pain after surgery:
TENS
How does TENS work?
Place electrode bw pain and s.c., inc amp until activating touch and not pain fibers.
Which have a lower threshold of activation, touch or pain fibers?
Touch, can be stimulated to decrease pain transmission
How long does TENS therapy last?
hours beyond the tx
Wide dynamic range of nociceptor dorsal horn projection cells:
signal presence of mild to extreme pain, there to signal the somatosensory cortex, primarily factual info
2 kinds of nociceptor dorsal horn projection cells:
Wide dynamic range (WDR) and Nociceptor specific (NS)
What do WDR dorsal horn projection cells respond to?
both touch and pain
WDR dorsal horn projection cells provide input primarily about:
the location and magnitude of the stimulus to the pwys, such as somatosensory cortex
Fxn of nociceptive inputs:
give you the emotional (affective) aspects of the pain experience
What do nociceptive specific cells respond to?
nociceptive inputs only
Nociceptive specific dorsal horn projection cells provide input primarily to:
the pwys associated w the affective (emotional) aspects of pain
Central sensitization:
CNS neurons that prone to firing bc of repeated or extremely painful stimuli (i.e. extreme activation of NMDA-type glutamate receptors, making the synapse stronger)
reinforce connection, making it permenantely stronger by the NMDA receptors:
Memory formation/ long term potentiation:
Pain that doesn’t have a visible cause:
neuropathic pain ie phantom limb pain.
Phantom limb pain generally starts with:
peripheral pain
What is the trigger for phantom limb pain?
Peripheral pain
What does phantom-limb pain set off?
over-stimulation w in s.c.
Causes of Phantom limb pain:
post-synaptic NMDA recep open bc of excess release of glutamate triggering long-term increases in strength of synapses OR trauma induces Sub P release from C fibers inhibiting post-synaptic K channels: extreme excitation
Other probable aspects of the causes of phantom limb pain:
gene transcription, new axon terminals, changes that propagate to higher levels of the brain
Mirror box therapy:
Look at normal arm mirroring the other arm moving it as if the damaged arm were in tact. Pain goes in a few weeks or months
Why are pain levels felt so variable depending on your emotional state?
Gating from higher levels
Descending pain-control pathways:
PAG activates rostral medulla, the off switch cells (in the RVM) activate dorsal horn opiate interneurons, pain transmission is reduced
T or F? Off cells project to dorsal horn making them less excitable, reducing the transmission of pain.
F. MORE excitable
Fxn of PAG:
Pain modulation
Locus Coreruleus:
projects to dorsal horn, releases NE, this reduces pain transmission, much like opioids do, inhibitory effect on dorsal horn
What activates the Locus Coreruleus?
PAG
These cells make it easier for pain info to reach higher levels:
proprioceptive cells in the rostal ventral medulla
T or F? The RVM has both on and off cells.
T
Fxn of on cells of the RVM:
pro-nociceptive action
What determines how much pain reaches consciousness?
Balance bw the 2 pain-control pathways, the on and off cell activity
Why should pain transmission pwys be open?
To keep protective reflexes at a useful level, in case you get cut, etc.
Where are opioid receps found?
on peripheral and central ends of pain fibers, on projection neurons, and now here in the RVM
T or F? Opiates inhibit the OFF cells.
F. Facilitate the off cells, opioids hit these cells and turns off pain
T or F? Opiates inhibit ON cells.
T
How do systemic opioids work?
by activating off cells at the RVM and mimicking inhibitory interneurons in the dorsal horn
Role of opiates under conditions of morphine tolerance:
they bc pronociceptive, causing pain
PAG has (few/many) opioid receptors.
many
PAG is turned on by:
the dorsal horn (turn antipain system on), anterior cinguate (emotional component of pain), and other ascending connections form the s.c.
Slow pain is assoc with what part of pain
the emotional aspect
Fast pain goes (here) and localizes where the pain is from.
to the somatosensory cortex
Is slow or fast pain associated with the localization of pain?
fast
T or F? Fast pain transmits a great deal of info regarding the magnitude of pain.
F. little or no info about this
The anterior cingulate is associated with this type of pain:
slow, perception of the emotional component of pain
Cingulate and the insula cortex is involved in:
mediating pain
Viscera sends pain to:
the insula
What is the insular cortex connected to?
the amygdala, for the emotional connection
The insular cortex is involved in:
pain consciousness, esp. visceral pain
Cannabinoids are similar in effects to:
opioids
How do cannabinoids work?
via G-protien coupled cannabinoid receptors
What is anandamide (AEA)?
One of several endocannabinoids (endogenous)
How do cannabinoids act on their target?
Increase in Ca++ in postsynaptic cell, if this synapse has a cannabis component, there will be a release of cannabinoids which go backwards to act on the cannabinoid receptors on the presynaptic cell (CB1 receptor), inhibiting their targets, reducing voltage sensitive Ca++ activity and NT release
Do cannabinoids work on the pre or postsynaptic cell?
pre, backwards transmitters “retrograde”, released from postsynaptic cell
2 ways cannabinoids inhibit their targets:
activate K channel activity or reduce voltage-sensitive Ca channel activity
How can we treat persistent neuropathic pain?
Cannabinoids
Where in the CNS are cannabinoids found?
Dorsal horn, RVM, and PAG
T or F? Cannabinoids and opioids are part of the same system.
F. seem to be 2 distinct systems: different sites in the PAG
T or F? Cannabinoids are coextensive with opioids.
F. They exist in a different locations and are 2 different systems.
What role do cannabinoids play in the periphery?
anti-nociceptive, nociceptors have cannabinoid receps
Inflammatory skin disease is related to:
renal failure, liver disease, and some cancers
T or F? Itch is a separate sense.
T
How is itch inhibited in the body?
s.c. has a set of inhibitory interneurons that inhibit itch (unresponsvie to pain)
Itch is a prominent feature of:
inflammatory skin disease
2 types of itch:
Chemical and mechanical itch
What fiber type is chemical itch stimulated by?
C-fibers
Examples of chemical itch:
allergic reactions, bug bites
Examples of mechanical itch:
scratchy sweater, bug walking on skin
What is mechanical itch mediated by?
C-fibers and low-threshold A-fibers
Migraine may be a result of:
cortical dysfunction
Where do migraines likely begin?
Trigeminal complex in cortex
Are men or women more prone to migraines?
women 18% vs. 6%
What do migraines lead to?
Change in blood flow in and around the brain
Rx for acute migraines:
agonist of serotoinin (5-HT(1B) and 5-HT(1D) receptors, BV constriction and prevents extravasation (reduce the inflammatory soup and decreaese the release of CGRP and substance P)
Long-term mgmt of migraines:
diet, lifestyle (i.e. chocolate can give some people migraines)
Phase 2 trials to treat migraines:
ABs to CGRP or CGRP receps
Tx for migraines involving behavioral techniques:
condition pts to activate their own anti-pain circuits
What can be used to reduce the intensity of migraine attacks?
Sympathetic system cues: temperature, sweating to reduce tension from pain (Biofeedback)
cyclooxygenase is aka:
COX-2
Fxn of COX-1:
Key player in inflammation, protects the GI tract, kidneys, and platelets, induced by injury
