L14 - pain (also revise D&D lecture for this) Flashcards
define pain
pain is a unique, unpleasant, sensory and emotional experience resembling actual /potential tissue damage
what are the sensory aspects of pain?
threshold of pain
intensity of pain
location of pain
what are the emotional aspects of pain
psychological aspects, eg
unpleasantness of stimulus and the emotions that evokes ( helplessness, fear)
which can escalate pain
describe the basic pain processing pathway
pain -> peripheral sensory nerves -> spinal cord -> cortex and limbic brain (pain perception) -> midbrain -> spinal cord (modification of pain we feel)
what brain region is associated with emotional aspect of pain processing
limbic brain
which brain region is associated with the sensory aspect of pain procesing
cortex
define nociception
the neural process of encoding noxious or potentially noxious stimuli
what are the 4 processes of nociception
transducton (stimulus to neurone)
transmission (peripheral neurones to brain)
modulation (descending inhibition)
perception
what sensory nerve fibres respond to noxious stimuli
(A delta) and C fibres
example of sensory nerve fibres do not normally respond to noxious stimuli
A beta
what are nociceptors
nerve endings in bodily tissues that can repsond to noxious stimuli and transduce them into receptor potentials
what inputs can nociceptors respond to?
mechanical
chemical
thermal
what is pain transduction
the coonversion of noxious stimuli to receptor potentials via nociceptors
describe process of pain transmission
process where pain message is carried from site of tissue injury to the brain (somatosensory cortex and limbic system) via axons of primary afferent nociceptor A∂ and C fibres
what is important to note about pain and transmission in the primary afferent fibre?
there can be pain percieved without transmisison in the PAF
there can be transmission in the PAF without pain being percieved
revise descending inhibition
x
list the key nuclei in the descending inhibition pathway ( and where theyre located)
periaqueductal grey (midbrain)
Locus Coereleus and rostral ventralmedial medulla (brainstem)
define acute pain
pain associated with tissue damage, shouldnt last longer than 3 months
serves a biological purpose - the pain prevents use of the damaged area, so it can heal effectively
define chronic pain
chronic pain lasting more than 3 months and outlasting the normal healing time for the tissue
serves no biological purpose
give examples of chronic pain
migranes
list two causes of chronic pain
peripheral sensitisation
central sensitisation
define peripheral sensitisation
increased sensitivity to afferent nerve stimulation
altered function of noicieptors
describe the process of peripheral sensitisation
nociceptors produce many neuropeptides.
neuropeptides have many effects including hyperalgesia, upregulation of existing and new receptors) and more
this makes the sensory nerve endings more sensitive and responsive to the NTs, reducing the threshold for nociceptor firing leading to elevated pain state)
give examples of neuropeptides released by nociceptors and the effects they have
substance P
histamine
5-HT
- primary hyperalgesia (making a pain stimulus more painful)
- allodynia (making a non painful stimulus painful)
- upregulation of existing and new nociceptors
define central sensitisation
amplification of pain by the CNS due to altered funcitoning of nociceptive neurones
what type of molecules can cause central sensitisation and how?
kinases
they alter activation kinetics of NMDA and AMPA receptors, and their trafficking to the membrane
this:
increases spontaneous neuronal activity
reduces threshold for receptor activation
including in pathways that are not normally nociceptive (eg A beta fibres)
what can central sensitisation lead to (sort of like symptoms)
pain when no pain stimulus is present
difference between peripheral and Central sensitisation
peripheral is due to altered responsiveness of nociceptors, central is due to increased activity of nociceptive neurones
peripheral, the pain is limited to site of injury, central it isnt
what are the types of pain
nociceptive (or inflammatory) -> from tissue damage
neuropathic -> from damage to pain system
other (central) -> due to neurological dysfunction (not damage)
what are the main inflammatory pain enhancers?
PGE2
PGI2
how do noxious factors activate nociceptors?
by increasing sensitivity and opening of VGNaC
by decreasing sensitivity and opening of VGKC
(in sensory neurones specifically)
leading to depolarisation and AP firing
list some noxious factors
prostaglandins bradykinins 5-HT ATP H+
describe process of neuropathy
a nerve lasceration, eg during surgery
damaged nerves cause firing and pain and nerves have a limited ability to heal themselves
so neuropathic pain often chronic
explain how NSAIs treat pain
- block COX enzymes reducing production of prostaglandins (noxious stimuli) - anti-inflammatory
- possibly also work in CNS where PGs have role in pain processing
- anti-pyretic effects from actions in CNS
what COX enzyme produces PGs
COX2
what COX enzyme inhibited by NSAIDs
both COX1 and 2
what effects does paracetamol have on symptoms
mild analgesic and anti-pyretic
describe proposed mechanism of paracetamol action
not entirely known, but
peripherally -> weak COX-2 inhibitor
centrally -> possibly due to activation of descending inhibiton pathways, but likely due to inhibtion of PG synthesis
how are analgesics used in neuropathy?
sometimes neuropathy can be due to dysfunction in channels of synapses / neurones (eg Na/K/Ca)
Ca2+ channels cannot be targeted as they are very widespread
Na channels can be targetted
