Lecture 25 - An Introduction to Pain Flashcards
A major concern is when acute pain becomes…
chronic pain - very difficult to treat
What are the different types of pain?
Nocioceptive - pin prick
inflammatory - hammer hit
Neuropathic - pain signal trapped in the nervous system = chronic pain
Describe Acute nociceptive pain?
Immediate, short duration, localised
NS is activated
relay, amplification, attenuation
Reflex withdrawal response
How is the transient potential receptor subunit (TPRV1) - ion channel pore related to pain?
responds to increases in acidity as well as capsaicin (the hot part of chili) and temperature
These are general nociceptors
What is the general tissue response to Acute injury?
cell lysis, acid H+, ATP releae
releae of mediators: seretonin histamine, PROSTAGLANDINS, cytokes
nociceptors activated and sensitised
localised pain hypersensitivity occures
What are the early and long term changes to nocioceptors?
early inflammation - amplification via receptor threshold and latency reduction
Long term changes - transcription mediated by cytokines and grwoth factors increase production of receptors, ion channels and neurotransmitters, causes Hyperalgesia (think about sunburn sensitivity)
What is allodynia?
“pathological response” e.g excruciating pain with light tough - NS has been over-activated and changed to chronic pain stage
What nerve fibres are involved in pain?
A-delta and C fibres - 70-90% of peripheral nerve
a-delta: Fast, sharp, acte, pricking localised pain mechanical and thermal pain
c fibres - slow pain aching, throbbing, burning pain, chemical pain
Looking at the doral root horn, what is the main excitatory neurtransmitter and which receptors are responsible for pain
Glutamate is main excitatory NT
GABA - is inhibitory NT
NMDA - when Mg2+ is displaced there is cellular remodelling (protracted nociception)
Which drug targets NMDA receptors?
Ketamine
What other senses inhibit pain?
Endorphins
Opioid receptors have a high concentration in the …
spinal cord
What can dampen pain signals going up the spinal cord?
Descending noradrenergic and 5-HT3 fibres
these can inhibit the spinal dorsal horn and dampen incoming signals
Amitryptilline simulates what?
The Descending noradrenergic and 5-HT3 fibres
Gabapentin act on a ____ channel in the spinal cord
calcium
Pain pathways project to ______ _____ and ___-_______ ___ ____
Superior colliculus and peri-acqueductal grey matter (PAG)
stimulation of PAG causes profound anagesia
endogenous opioids activate this area
This forms the basis for deep brain stimulation of intractible pain
What happens when a patient has chronic pain?
There is an excessive pain response, leading to abnormal hyper-excitability and structural remodelling = phenotypic change
pain signal EMBEDDED within NS
15-20% can develop chronic neurpathic pan after traumatic injury
pain genes can determine pain response
What is the ‘Stargazer gene’ (CACNG2)
a mutation in stargazin protein
mouse had absense seizures and ataxia in addition to susceptibility to neuropathic pain
The human CACNG2 is associated with…
chronic pain! same gene as the one in mouse - research underway…
How can genetics lead to lack of sensitivity to pain?
mutation in Na, 1,7 receptor gene - one of the key trasnmitters of pain
What enzyme allows the conversion of codeine to morphine?
liver enyme CYP2D6
What are the types of analgesic medication?
Opioids (mainstay for severe and moderate pain) - morphine
paracetamol
Aspiriin
NSAIDS
others
What are opioid side effects?
Ventilatory depression
drowsiness and sedation
nausea and vomiting
What are some pain management stragegies?
Multimodal analgesis - use of smaller doses of opioids in combination with other analgesis drugs
Pre-emptive analgesia - prior to surgery (thery: attenduate injury and neuroplastic repsonse
target nerve transmission - local anaesthesia (Lignocaine)
Remove cognition - general anaesthesia
