topic 5 - pain and pain suppression Flashcards
(30 cards)
what are nociceptors?
receptors of damage
can have highly myelinated axons and unmyelinated axons
highly myelinated axons covey mechanical pain quick and precisely = early pain and informative of location. whereas unmyelinated axons convey diff kids of pain slowly and less precise = late pain. vague location. can be sensitive to extremes of mechanical stimulation, pungent irritants, and temperature, acid and capsaicin
what are prostaglandins
made as part of the inflammatory response to damage and increase vasodilation increasing blood flow to skin surface
what is the somatosensory pathway
- in the dorsal root of the spinal cord substance P is released alongside glutamate (substance P is a co-neurotransmitter) and allows for pain to be felt
what is the dual brain mechanism for pain perception?
primary somatosensory cortex causes the physical pain sensation and the anterior cingulate cortex causes an immediate unpleasant perception
what is hypnosis-induced analgesia in pain perception?
experiment where hands are placed in 45 degree water this is hot enough to hurt but not cause damage. the brain was then scanned for a response. increased activity in the anterior cingulate cortex. the brain region ‘hypnotised’ the individual against the pain. there was a higher pain sensation response in the somatosensory cortex however the response in the ACC (perception of pain) was lower
describe the descending analgesia circuit using your shit notes (pre brain)
nociceptors in the periphery detect damage through free nerve endings throughout the skin, fingers and toes. These free nerve endings converge into an axon (nociceptors). under high pressure the sodium gated channels open in the the nociceptors allowing sodium into the cell action potential goes from -70mV to -30mV opening voltage-gated Na+ channels causing depolarisation and an AP. Nociceptors sit in the dorsal root ganglion of the spine. AP reaches the presynaptic terminal in the dorsal root ganglion. vesicles containing the neurotransmitters Substance P and glutamate are released across the synaptic cleft. glutamate binds to the receptors (ligand-gated Na+ channels) which causes a new AP which travels to the brain.
describe the descending analgesia circuit using your shit notes (in brain)
the brain receives a pain signal so sends signal down descending neurone to release serotonin. second neurone releases opiates. this then inhibits the initial action potential of a pain signal
(now in peri aquaductal grey in the midbrain) (involves inter neurones and projection neurones) GABA inhibits projection neurone due to bind with chloride channels. causing the membrane potential to hyperpolarise = no AP :(. due to no AP no calcium enters causing depolarisation but this also causes no vesicles to released and no more GABA being released. and we circle back. projection neurones can depolarise again as there’s no GABA present. AP can travel down the PAG neurone to the Raphe magnus (nucleus in medulla) where glutamate is released causing the membrane potential to be positive. Raphe nucleus axon makes synapses in dorsal horn of spinal cord - all vertebrae pain location not specific). in the spinal cord there is a population of inhibitory interneurones which connect to the synapses from the raphe nucleus. vesicles release serotonin and noradrenaline across this synaptic cleft. interneurones = inhibitory but the serotonin receptors they make are excitatory allowing for depolarisation
last step of the descending analgesia circuit: what are the two target of the interneurones in the dorsal horn?
1) first order neurone –> releases endogenous opiods which cause the first order neurone to hyperpolarise making a AP less likely
2) presynaptic terminal –> inhibits serotonin causing the terminal to hyperpolarise = no AP
placebo affect - pain suppression
- participants given placebo skin cream to reduce their pain. this lead to activation of the dorsolateral prefrontal cortex which then activates the peri-aqueductal grey matter and activates the descending analgesia circuit
acupuncture - pain suppression
- act on the descending analgesia circuit
- tested using naxolone an opiate receptor blocker
- if given acupuncture naloxone wont work
if given naloxone acupuncture wont work
because DAC needs opiates to work
capsaicin and pain suppression
- used for muscle pain through skin
- causes lots of substance P to be released so it runs out at the synapse and causes half hour ish of no pain
NSAIDS and pain suppression
- non-steroidal anti-inflammatory drugs
- aspirin, ibuprofen, COX-2 inhibitors
- act peripherally - poor blood brain barrier penetration because of binding proteins in the blood
- mechanisms of action: inhibition of cyclo-oxygenase 1 and 2
- reduction in production of prostaglandins
- Side effects
–> COX-1 involved in blood clotting: aspirin prevents blood clotting
–> COX-1 involved in protection of stomach lining from acid: NSAIDs bad for stomach
Paracetamol and pain suppression
- reacts with endogenous molecules to form AM404, agonist of TRPV1 and CB-1 cannabinoid receptors
- TRPV1 channels found on nocicepetors
- CB-1 receptors are found in many central and peripheral pain-related circuits, including DAC where they reduce inhibition
opiates and pain suppression
- opium = smoked or eaten
- morphine = many different ways; only 20% crosses blood-brain barrier half life of 3-4hrs
- codeine = oral
- heroin = injected, lipid soluble so crosses blood-brain barrier more
- oxycodone = pills with either fast or slow uptake
- fentanyl = higher powerful synthetic opiate - highly lipophilic - half life 3-7hrs
opiate short term effects
- relieve pain, cough, diarrhoea
- induce hypothermia
- induce sleep
- stimulate pleasure
physiological action of opiates
- opiate drugs mimic the action of endogenous opioids: endorphins
- bind to endogenous opioid receptors, which can be found in many places in the body and the brain
where are opioid receptors (MCQs connections)
in the brain
- preoptic area - hypothermia
- mesencephalic reticular formation - sedation
- locus coeruleus - sedation
- ventral tegmental area and n.Accumbens - rewarding
- peri-aqueductal grey area - pain relief, pleasure
- brain stem - coughing centre, breathing reg
long term effects of opiates
- mild whilst drug being taken
- constipation
- pupil constriction
- menstrual irregularity
- reduced libido
heroin withdrawal symptoms
- begin 6-12 hrs after last dose and last 7 days ish
- restlessness
- watering eyes
- chills, shivering
- nausea, vomiting
- tremor
- runny nose
- sweating
- gooseflesh
- diarrhoea
- muscle spasms
counteracting withdrawal symptoms of heroin
- more heroin
- methadone - wean-able opiate
- acupuncture
- avoid drug-related contexts
opiate addictiveness
- affect the mesotelencephalic dopamine system and ventral tegmental area (VTA)
- opiates inhibit GABA-energic interneurones
- this releases inhibition from neurones whcih project to nucleus accumbens
- more dopamine released
- Nucleus accumbens: effects independent from but similar to dopamine from VTA
cannabis and pain suppression
- made of THC and CBD
- both lipid soluble and easily cross blood-brain barrier
- easily stored in fat tissue and have half life of 7 days
- less withdrawal due to slow half life
what are the short term effects of cannabis
?
recreational use:
- reduction in anxiety
- dissociation of ideas
- heightened sensation
- distorted sense of time - seems slower
- intense emotional experiences
- hallucinations - infrequent
medicinal use
- reduces nausea
- increase in appetite
- dilation of bronchioles
- blocks seizures
- decreases severity of glaucoma
- reduces pain
intoxication
- uncoordinated
- slower reflexes
- longer than alcohol
attention and STM probs
panic attacks
paranoia
no realistic lethal overdose
physiological action of cannabis
- THC - partial agonist of CB1 (brain) and CB2 (immune system) receptors. psychedelic effects
- CBD - antagonist on CB1 receptors. interacts with many other receptors in the brain
- dont know how two react
