9 - pain/sensory Flashcards
what is neuropathic pain
pain caused by damage to somatosensory nervous system
nerve injury
types of neuropathic pain
allodynia
dysesthesia
dysesthesia
abnormal or unpleasant sensation felt when touched, caused by damage to peripheral nerves
types of dysesthesia
motor
sensory
sensory neuropathy
tingling numbness shooting pains unable to detect hot or cold pain affect nerves that control feeling
motor neuropathy
affects motor nerves (nerves that control muscles)
muscle weakness/wasting
muscle twitching/paralysis/cramps
how do you treat neuropathic pain
antidepressants
anticonvulsants
corticosteroids to relieve pain/pressure
spontaneous pain
occurs in the absence of a stimulus
2 types of spontaneous pain
continuous
paroxysmal
continuous spontaneous pain
steady and on-going (often felt on skin)
ranges from pins and needles sensation to cramping and aching
paroxysmal spontaneous pain
intermittent pain
no precursor
shooting or stabbing sensation
what is phantom pain
perception of pain relating to a limb/organ that is not physically part of the body
potential mechanisms for phantom pain
abnormal growth of injured nerve fibres
neuromas
central sensitisation
what are neuromas
growth/tumour of nerve tissue
formed from injured nerve endings at stump site and fore abnormal action potentials
central sensitisation
increased excitability of dorsal horn neurons
treatment of phantom pain
antidepressants
anticonvulsants
narcotics - opioid
NMDA R antagonists - block Glu
spinal cord stimulation
hypnosis
acupuncture
mirror box visual feedback
use of antidepressants to treat phantom pain
modify neurotransmitters
help you sleep
what can anticonvulsants be used to treat
epilepsy quiet damaged nerves seizures bipolar disorders neuropathic pain
what is a convulsant
production of a sudden involuntary muscle contraction
how do anticonvulsants work
suppress rapid firing of neurons block Na+ channels increase GABA signalling block Glu receptors inhibit Ca2+
effect of increase GABAa activity
Cl- influx
hyperpolarisation
effect of increasing GABAb activity
inhibition of VOCCs
opening of GIRK channels
reduce excitability
role of sensory neurons
afferent neurons that transmit sensory input to CNS
convert external stimuli to electrical impulses
what do sensory neurons connect with in the cns
interneurons
examples of sensory receptors
mechanoreceptors photoreceptors chemoreceptors thermoreceptors nociceptors
mechanoreceptors
sensory receptor that responds to mechanical pressure
e.g. touch, auditory vibrations, vestibular
photoreceptors
rods and cones in the retina
sensitive to light
chemoreceptors
peripheral chemoreceptors - in blood (aortic and carotid bodies)
central chemoreceptors - detect pH of csf
neuromuscular blocks (NMB)
block neuromuscular transmission at the neuromuscular junction
causing paralysis of the affected skeletal muscles
when have you achieved a full neuromuscular block
when the muscle is no longer responsive to ACh released by motor neurons
depolarising NMB mechanism
ACh receptor agonist
NMB binds to ACh receptors, outcompetes ACh
cation influx causes membrane depolarisation
NMB not degraded by AChE
ACh receptor desensitised
prevention of further action potentials
why do depolarising NMBs cause constant depolarisation
NMB is not broken down by AChE
non-depolarising NMB mechanism
ACh receptor anatagonist
NMB prevents sufficient binding of ACh to its receptors
prevents normal downstream depolarisation events
vision receptos
detect and interpret light stimuli
wavelenght 400-750nm
rods function
for seeing in the dark
function in less intense light
concentrated at outer edges of retina
used for peripheral vision
rod structure
long rectangular outer segment made of double membrane discs
photoreceptive pigment = rhodopsin
cone cells
interpret colour vision function best in bright light
cone structure
shorter triangluar shape outer segment
what causes hyperpolarisation of photoreceptor membraen
closure of VOCCs
what is released when photoreceptor membrane hyperpolarises
glutamate
describe the excitatory response in photoreceptor membrane
Glutamate causes decreased excitatory response at ionotropic receptors
inhibition of horizontal cells and bipolar cells due to hyperpolarisation
describe the inhibitory response in photoreceptor membrane
glutamate causes decreased inhibitory response at metabotropic receptors
excitaton of bipolar and horizontal cells due to depolarisation
where are hearing receptros found
mechanoreceptors on Organ of corti in cochlea
mechanism of hearing
outer hair cells contract in sync with sound and amplify signal
inner hair cells transduce mechanical signal vibration into an electrical signal
open mechanically gated K+ channels
hair cells
the sensory receptors of the auditory and vestibular systems in the ears
where are auditory hair cells found
spiral organ of corti on basilar membrane on cochlea in inner ear
role of outer hair cells
mechanically amplify low-level sound that enters the cochlea
auditory nerve
relays electrical signals transduced from inner hair cells to auditory brainstem/cortex
cochlea
part of inner ear
recieves sound causes stereocilia to move
creates electrochemical potential between sections
important for mechanical sensing an K+ flow
organ of corti
made up of hair cells
lies between tectorial and basilar membranes
3 bones of middle ear
malleus
incus
stapes
role of bones in middle ear
vibrations introduce pressure waves into the ear
these waves are amplified by hair cells
thermoreceptors
slowly adapting receptors that detect changes in skin temperature
transient receptor potential (TRP) channels
when activated, allow depolarisation of the neuron via Ca2+
when skin is above 36 degrees
warm receptors activated
cold receptors quinescient
nociceptors
sense noxious and harmful stimuli that require a response
types of nociceptors
thermal/mechanical
polymodal
what supplies thermal/mechanical nociceptors
large, fast, myelinated A-delta afferent nerve fibres
pain felt by activation of thermal/mechanical nociceptorsq
fast response
e.g. stabbing pain
what supplies polymodal nociceptors
unmyelinated C fibres
pain felt by polymodal nociceptos
slow response, dull, aching pain
polymodal nociceptors
perform different functions in combination
2 phases of pain
phase 1 - medaited by fast, A-delta fibres
phase 2 - polymodal, slow C fibres
nociceptors have free nerve endings
not connected to specific nerve
connected to area of the body
effect of inflammatory mediators on nociceptive signal
increase the nociceptive signal
e.g. protons/ATP/histamine
released from tissue damage
what is pKa
measure of acid strength
the dissociation/ionisation constant
when does drug ionisation occur
when drugs are dissolved in aqueous solution to weak acidic or basic solutions
lower pKa means
more acidic
H+ lost more easily
lower Ka means
less acidic
Ka equation
[H+][A-] / [HA]
can ions pass passivley through membranes
no
what is peripheral sensitisation
increased sensitivity to afferent nerve stimuli
hypersensitivity
can be allodynia or primary hyperalgesia
mechanisam of peripheral sensitisation
reduction in threshold
increase in responsiveness of peripheral ends of nociceptors
expression on a-adrenoreceptors
inflammatory chemicals released
secondary hyperalgesia
changes to pain thresholds in the undamaged tissue surrounding the injury, which can become hypersensitive to touch
central sensitisation
allodynia
peripheral sensitisation
pain threshold decreases
pain from stimulus that normally wouldnt cause pain
primary hyperalgesia
peripheral sensitisation
changes in the area of injury
responsiveness increases
pain is prolonged and exaggerated
central sensitisation
increase in excitability of neurons in the cns
can cause secondary hyperalgesia
cause of chronic pain
central sensitisation
NS in persistent state of high reactivity
mechanism of central sensitisation
burst of nociceptor activity
strength of synaptic activity changed
different cns neurons activated that would normally only respond to noxious stimuli
role of spinal cord areas in withdrawal reflex
sensory neuron sends signal/enters via dorsal-horn of spinal cord
motor neuron leaves cns via ventral horn
types of pain conduction
A-delta fibres
C fibres
A-delta fibres
large, fast, myelinated
sharp, stabbing pain
C-fibres
small, slow, unmyelinated
burning, aching pain
interneurons in pain perception
1 type of neuron lets information into brain
1 doesnt
different amounts of the 2 interneurons lead to different perceptions of pain
causes of decreased pain threshold
sensitisation
neuronal plasticity
causes of increased pain threshold
habituation
where do pain fibres enter spinal cord
dorsal root ganglia
what do pain fibres cause release of
glutamate release
acute pain
sharp, short-lasting
directly related to soft tissue damage
chronic pain
due to sensitisation of soft tissue damage
types of Glu receptor
NMDA
AMPA
Kainate
mGluR
excitotoxicity
neuronal damage due to prolonged Glu synaptic transmission
synthesis of GABA
from glutamate
enzyme = glutamate decarboxylase
glycine
amino acid neurotransmitter
synthesised from serine
NMDA agonist
opioids
drugs involved in analgesia - modulate nociceptic signalling
cause Gi/o signalling
inhibitory effect
examples of metabotropic receptors
muscarinic cholinergic receptors (M1-M5) adrenergic receptors (a1, a2, b1, B2)
ideal pain killers
liquid at room temp high receptor-binding affinity high bioavailability ample potency low solubility in blood tissues
overall action of botox
prevents ACh release at NMJ to decrease muscle contraction
botox heavy chain
allows botox protein to bind and enter pre-synaptic neuron via plasma membrane
botox light chain
acts as a protease
cleaves SNARE proteins required for vesicle docking (SNAP-25)
botox mechanism more detail
heavy chain allows botox to enter pre-synaptic
light chain cleaves SNAP-25
NT-filled vesicle cannot dock to membrane
no ACh released
no muscle contraction
medical uses of botox
treat uncontrolled blinking
treat muscle spasms
treat overactive bladder
reduce wrinkles
volume of distribution
volume of liquid required (containing total drug) to match concentration of drug in blood plasma
the degree to which a drug is distributed in body tissue rather than the plasma
volume of distribution equation
total amount of drug in the body / drug blood plasma concentration
higher Vd
= greater amount of tissue distribution
characteristics of drugs with high Vds
low ionisation
high lipid-solubility
low plasma-binding capabilities
what may increase Vd
liver failure kidney failure (fluid retention)
why may decrease Vd
dehydration
clinical uses of Vd
determining drug dosages for desired blood concentrations
estimating blood concentrations when treating overdose
total drug clearance is
the volume of plasma which contains the the total amount of drug removed from the body per unit time
how do you calculate rate of drug elimination
plasma concentration x total clearance
when is clearance at a steady state
when rate of input = rate of elimination
what causes drug elimination
liver metabolism
kidney excretion
how do you determine drug clearance
measure teh plasma concentration at intervals during constant rate IV infusion until a steady state is reached
how do you calculate drug clearance
rate of elimination of drug / conc. drug left in body
drug half life
how long it takes to lose half of a drugs activity
low clearance =
less drug in urine
more drug in body
neostigmine
drug that inhibits acetylcholinesterase
effect of neostigmine on action potentials
AChE blocked
ACh not broken down
threshold level reached
new AP triggered
clincial use of neostigmine
treatment of myasthenia gravis
treatment of urinary retention
myasthenia gravis
not enough ACh receptors
causes weakness in skeletal muscles
autoimmnue disease
