sodium channels and pain 1 Flashcards
what is pain defined as?
- pain is an unpleasent sensory or emotional experience associated with actual or potential tissue damage.
give stages of how pain is reached by the brain?
-injury/stimulus
-peripheral nerve
TRANSDUCTION
- dorsal root ganglion
CONDUCTION
- dorsal horn of spinal cord
- ascending pathway
TRANSMISSION
-brain
-descending pathway from brain to spinal cord - coordinates response
what is nociception?
PArt of pain pathway but the stage before the brain becomes involved?
give steps of a spinal cord reflex?
- sensory receptor
- afferent pathway
- integrating centre
- efferent pathway
- effector organs
what is a DRG neuron and what do they do?
- DRG is dorsal root ganglion neuron
- relay information from the periphery to the spinal cord
what is noxious stimuli?
Stimuli which is an actually or potentially tissue damaging event
what is non-noxious stimuli?
stimuli which has no potential tissue damage - e.g. touch
explain why DRG are part of a heterogenous population
- because DRG come in different sizes
- they can respond to different stimuli
what do different sizes of DRG respond to?
- large - non-noxious stimuli e.g. touch
- medium - noxious stimuli -pain sensing (nociceptive)
- small - noxious stimuli - pain sensing (nociceptive)
what are the 3 key components in pain sensing?
- transduction
- conduction
- transmission
what are the different myelination of nociceptors?
Ab - thick
Adelta - thin myelination
C- no myelination
what is transduction?
- exchange of one physical stimulus to another - sodium in neuron reach a threshold for Nav to get involved and to reach an AP
- from skin to nerve?
what is involved in the conudction of pain?
-dorsal root ganglion conducts to SC?
what is involved in the transmission of a pain stimulus?
- spinal cord central termini
Define accute pain
acute pain alerts the body of chemical,thermal or mechanical stimuli which has the potential to damage the body
- has a protective role
Define chronic pain?
- pain which persists - usually accompanies chronic inflammatory conditions
- neuropathic pain results from damage to the nerve, which can be caused by trauma , diabetes, cancer treatment and herpetic infection.
how many people are said to be suffering from chronic pain?
19% of europeans suffer moderate to severe chronic pain
-50% of those feel there is an unmet therapeutic solution to chronic pain
What are NSAID?
- non-steroidal anti-inflammatory drugs
- inhibit COX enxymes (which produce prostaglandins)
- side effect - GI tract irritation
- limited use on peple with heart, renal conditions and diabetes.
what are opioids?
Class of drugs which bind to opioid receptors in the CNS, PNS and GI tract.
- have short term side effects
- build up tolerance and develop a dependence on them.
why is pain important?
pain is important as it has a protective role - if cannot sense pain you cannot sense tissue damage - this means people are unaware that they are harming there body
- results in infection or loss of limbs/finger and deformities etc
GOAL IS TO RELIEVE PAIN BUT NOT TO ABOLISH IT COMPLETELY.
give conditions in which patients feel extreme pain
- PE (primary ethermalgia)
- PEPD (paroxysmal extreme pain disorder)
-feel pain when chewing + defecating
(dominant??)
give conditions in which patients have the absence of pain
CIP - complete insensitivity to pain
recessive
Why are Voltage gated sodium channels (VGSCs) concerned with pain?
- VGSCs are essential for the excitability of mucles and nerves
- concerned with the conduction of pain
- VGSC’s are major targets for local aneasthesia and epilepsy
- with absence of VGSC’s = hypoexcitability/silence
- inherited pain disorders linked to mutations in VGSCs
how many VGSCs are there?
9
Nav1.1 to Nav 1.9
what differs between different VGSC s/alpha subunits?
- activation and inactivation properties vary
- different neurons can fine tune excitibility
- expression patterns and levels differ
- are specialisations to where different alpha subunits are expressed
Where are Nav1.7-1.9 expressed?
exclusively in PNS
good targets for pain therapy
Where are Nav 1.1, 1.2, 1.3 and 1.6 expressed?
in both the PNS and CNS - but dont want to target these for pain therapy as are not PNS specific - don’t want to disrupt CNS