Flashcards in Neuropathic Pain Deck (66):
an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or describe in terms of such damage
What are the 2 versions of pain?
Chronic (long term)
Acute (short term)
Is there treatment for chronic pain?
NO. you can only reduce the pain to a tolerable level that will not interfere with their daily function
What are the two main types of pain?
Nociceptive - pain associated with trauma, injury and inflammation (what we all think pain is)
Neuropathic - chronic pain syndrome that is associated with sensory abnormalities like numbness, tingling OR for example it may feel like you have a glove on (hand is warmer than the body)
Describe the pain processing loop in very basic terms.
Primary afferent (comes into the body) and carries pain impulse to the spinal cord, which relays info to brain. The brain then releases anti-pain sensing back to the spinal cord and then again to the site of injury.
What can chronic pain be caused by?
drug, disease, or injury that induces damage to the sensory fibres involved in the pain processing loop
What are some triggers of neuropathic pain?
What nerve fibres are associated with pain and temperature? Describe them as well please.
Aδ - small, myelinated
C - small, unmyelinated
*these are peripheral afferent fibres
What are the nerve fibres associated with touch and vibration?b Describe them as well please.
Aβ - large, myelinated
*Aβ in chronic pain start shooting chronic collaterals off of main root. Some of these hit the laminae 2 which means they are signalling the brain that the patient is in pain again.
Afferent = ?
coming into the spinal cord (dorsal)
Efferent = ?
leaving spinal cord (ventral)
Where are cortical neurons? When are they excitable?
In the brain.
Where are dorsal horn neurons? When are they excitable?
In spinal cord.
In neuropathic pain.
What is resting membrane potential of a cell?
Bc the cell membrane is actually more permeable to K+, the Ek is actually closer to -90 mV. How is this corrected back to the actual -70 mV?
3 Na+ out
2 K+ in
At rest, what ion(s) are high intracellular ?
At rest, what ion(s) are high extracellular ?
Ca2+, Na+ and Cl-
When the cell becomes more _____, that is what causes pain.
*whatever happens to make the cell more POSITIVE is what causes the pain response.
*whatever we can do to make the cell more NEGATIVE with stop the pain response.
So if we blocked Ca and Na channels, what would happen?
stop pain! :)
So if we blocked Cl channels, what would happen?
Pain would still be present :(
What would happen if we increased the flow of potassium (remember it flows from inside to outside of the cell)
stop pain! :)
What type of neurotransmitters bind to receptors and cause opening of Na and Ca channels?
How do anti-epileptic drugs work?
Block Ca and Na channels - therefore surpress pain
Describe the natural flow of ions.
K+ flows out.
Na+, Ca2+, Cl- flow in.
Describe action potential
-a stimulus causes depolarization
-Na+ channels open and Na+ flows into cell
-cell becomes more positive (depolarizes)
-if cell depolarizes to the threshold, an action potential will result
-Na+ channels close, K+ channels open
-Em returns to resting potential
*there is a refractory period following an AP when Na+ channels won't open
What do excitatory neurotransmitters do?
Give examples please.
-bind to post synaptic receptors and cause depolarization
ex. glutamate (Aδ fibres), Substance P (C fibres) and aspartate
What do inhibitory neurotransmitters do?
Give examples please.
-bind to post synaptic receptors and cause hyper polarization
ex. GABA, glycine (inter-neuronal fibres)
What can hyper excitability be caused by?
-enhancement of excitatory mechanisms
-loss or reduction in inhibition
What happens when cell permeability increases?
-Na+ increases intracellularly
-Ca2+ increases intracellularly
* when the intracellular conc of these ions increases, depolarization occurs and neutrons fire!
Describe the pathophysiology of "windup" (slide 13)
Pretty much you want to treat early because one abnormal cell activates other cells which can turn into a big tumor.
*Windup occurs when adjacent neurons produce AP in response to ectopic firing therapy increasing the strength of the pain signal
Again, what are the excitatory neurotransmitters?
Again, what are the inhibitory neurotransmitters?
What receptor does glutamate affect?
What receptor does aspartate affect?
Ca2+ and Na+ are affected by _____ transmission.
Cl- and K+ are affected by ________ transmission
T or F: a GABA agonist is beneficial in pain management
* GABA either increases Cl- influx or K+ efflux (both of these will make the cell less positive, resulting in pain suppression)
T or F: a drug that was an NMDA receptor blocker is not beneficial in pain management
* NMDA allows Na+ to flow into the cell (this would make the cell more positive so if we block this receptor, it is stopping a positive flow from coming into the cell so it would be beneficial in pain management)
AMPA receptor causes leakiness of what ion into the cell?
What effect does a GABA-A receptor have?
opens Cl- channels
What effect does a GABA-B receptor have?
opens K+ channels
closes Ca2+ channels
The neurotransmitters adrenalin, serotonin, and endogenous opioids all produce what effect?
T or F: symptoms of neuropathic pain are extremely predictable
False man - they are very unpredictable
What do neuropathic pain symptoms vary greatly depending on???
What are symptoms of neuropathic pain?
Note** - these are sensory symptoms, not nociceptive!
pain due to stimulus that doesn't normally provoke pain
*exaggerated pain symptoms from non-noxious stimuli
pain response greater than usual to a stimulus that is normally painful
*exaggerated pain symptoms from noxious stimuli
Abnormal numbing or prickling or skin
*pins and needles
What are the 3 things involved in the pain triad?
What additional disorders can chronic pain sufferers usually develop?
-lack of conc
Describe the DN4 questionnaire used to diagnose neuropathic pain
-Q's with Y or N answer
-total of 10 Q's
-Pt must score 4 or more to classify pain as NPP
Describe the visual analogue scale used to diagnose neuropathic pain
Pt's are asked to rate pain on a scale of 0-10
0 = no pain
5 = moderate pain
10 = worst pain
What are the 4 main points of focus for treating NPP (neuropathic pain) ?
1 - inhibition of first order sensory afferent
2 - synaptic inhibition between 1st order sensory afferent and DRG
3 - synaptic inhibition between DRG and dorsal horn interneurons
4 - synaptic inhibition between dorsal horn interneurons and ?? (slide cut off)
How can the action potential of a cell be regulated to treat NPP?
Describe decreasing excitation
Na channel blockers, inhibiting calcium channels or blocking excitatory receptors
Describe increasing inhibition
GABA agonists, inhibition of serotonin and noradrenalin reuptake
How do anti epileptics work to treat NPP?
-reduce influx of Na+ and Ca2+
-enhance inhibitory effects like GABA
-reduces conc of glutamate and/or blocks NMDA receptor
What is an example of an anti epileptic drug?
*it blocks N type calcium channels
How do tri-cyclic anti depressants work to treat NPP?
-block reuptake of noradrenalin and serotonin
-blocks Na+ and Ca2+ channels and NMDA receptors
How do SSRI (selective serotonin reuptake inhibitors) anti depressants work to treat NPP?
-inhibits serotonin reuptake without affecting noradrenalin
Describe examples of topical anti-neuralgic agents and how they work to treat NPP.
-exact mechanism is unclear however it has been proposed that these products desensitize afferent neutrons by depleting the release of substance P
ex. capsaicin ointment or lidocaine
What are first line treatments?
-anti-depressants (tri-cyclic or SSRI)
-topical anti-neuralgic agents
What are second line treatments?
What are third line treatments?
What are fourth line treatments?