topic 5 - pain and pain suppression Flashcards
types of nociceptors
Highly myelinated axons (Aδ fibres) convey mechanical pain very quickly and precisely: early pain. This is informative about location.
Unmyelinated axons (C fibres) convey different kinds of pain more slowly and less precisely: late pain. This is vague about location.
- C fibres can be sensitive to pungent irritants (mustard oil) and capsaicin
prostaglandis
- molecules that help with inflamation and fight off invaders
- senstise the free nerve endings therefore pain perceived in that area is stronger
Somatosensory pathways
- incoming nociceptor has a cell body in the dorsal root ganglion and they make a synapse in the dorsal horn of the spinal cord. Glutamate is the main neurotransmitter used in that synapse and substance P as a co-neurotransmitter (substance p used as an amplifier)
- that first CNS sensory neuron’s axon runs across other side of spinal cord, through medulla and through the mid brian and makes a synapse in the thalamus (ventral posterior nucleus)
- neurons from the thalamus make synapses onto the neurons in the primary somatosensory cortex which tells us where the pain is
- pathway that it comes through tells us there is pain - if it doesn’t make it to the brain it is not pain.
phantom limb
feeling of pain in a lost limb due to it still being represented in the brain
Dual brain mechanisms
Pain sensation (physical) - coded in the primary somatosensory cortex.
Unpleasantness perception (emotional) - anterior cingulate cortex.
how to treat phantom limb pain
mirror with good limb seeing it being treated
hypnosis induced analgesia
pain with sticking ur hand in rly hot water
hypnosis reduced pain of uncomfortablness by reducing activity in the anterior cingulate cortex
pain suppression - non-drug approach
- direct stimulation of the PAG
- stressful situations (soldiers etc)
- placebo effect
- acupuncture (tested using naloxone)
what blocks opiate receptors
naloxone, also used for heroin overdoses
Capsaicin
- used topically on skin for muscle relief (deep heat)
- hot sensation depletes substance p
NSAID
anti-inflamatory drugs
inhibit the enzymes that make prostaglandins - reduction in prostaglandins production
NSAID side effects
COX1 - involved in blood clotting: aspirin prevents blood clotting. involved in protection of stomach lining from acid: NSAID bad for stomach
paracetamol
works through CB-1 receptors (cannabis)
morphine usage and half life
half life - 3/4 hours only 20% crosses blood-brain barrier
heroin usage and half life
0.1-0.25 hours half life, lipid soluble so easily crosses blood-brain barrier
morphine usage and half life
3-4 hours half life, 20% crosses barrier
oxycodon half life
4.5 hours half life
Fentanyl half life
3-7 hours
opiates short term effects
- relieve pain
- relieve cough
- relieve diorhea
- induce hypothermia
- induce sleep
- stimulate pleasure
opiates physiological action (how do they work)
- mimic the action of endogenous opioids: endorphins
opioid receptors
3 major subtypes:
- delta
- kappa
- mu
maybe learn where they are and what for
opioids on the periaqueductal gray matter in mid brain ( in the descending analgesia circuit DAC)
the inhibit activity of inhibitory neurons
opioids on the spinal cord in the DAC
block the incoming pain signals
opiates long term effect
mild as long as taken.
you will be:
- constipated
- reduced libido
- pupil constriction
- menstrual irregularity
But you will have withdrawals
You get all the pleasure you need so might not take care of yourself etc
Heroin withdrawal effects
begin 6-12 hours after last dose, stop after around 7 days
Includes:
- restlessness
- runny nose
- sweating
- muscle spasms
- tremor
- vomitting
- sweating
how to deal with heroin withdrawals
- avoid drug-related context
- take more drugs
- methadone
- acupuncture
opiate addictiveness
in Ventral tegmental area (VTA):
- opiates inhibit GABA-ergic interneurons
- this releases inhibition from neurons which project to nucleus accumbens
- more dopamine release
In nucleus Accumbens:
-effects independent from but similar to dopamine from VTA
cannabis usage
- 20-50% taken up from smoke, less from ingested (6%)
- very lipid soluble and easily crosses the blood-brain barrier
- easily stored in fat tissue, half life of 7 days
cannabis short term effects
Recreational use:
- reduction in anxiety
- dissociation in ideas
- heightened sensations
- distorted sense of time (goes slower)
- intense emotional experiences
- hallucinations (infrequent)
Medical use:
- reduces nausea
- increase in appetite
- dilation of bronchioles
- blocks seizures
- decreases severity of glaucoma
pain relief:
- as effective as opiates for acute pain
- greater potency and efficiency than opiates for chronic pain (but side effects)
- sites of action include:
peripheral nerves
direct spinal chord activity
descending analgesia circuit
anterior cingulate cortex
cannabinoid receptors
highest concentration exist in the hippocampus
function of endocannabinoids
- released from the POST synaptic side of synapse and bind with pre synaptic side
- work in close vicinity of other synapses
- suppresses the pre-synaptic release of neurotransmitters
- in the hippocampus, this affects GABA, hence suppressing inhibition: depolarisation-induced suppression of inhibition (DSI)
DSI
-endogenous cannabinoids released from post-synaptic terminal when depolarised
- cannabinoids sit on pre-synaptic terminals of other synapses
( i dont rly get this)
person who doesnt feel pain
- burns herself on stove without realising
- defect in the FAAH enzyme (breaks down anandamine (linked with cannabinoids))
cannabis long-term effects
- problems associated with smoking
- impairments in memory recall
- impairments in attention
- slower decision making
- if taking skunk - increased odds of psychosis by up to 5x
- decline in IQ with persistent use (age 13-39)
- especially vulnerable if starting in adolescence
physical dependance on cannabis
- tolerance develops during extended use but withdrawls are rare
- long-term users may experience sensitization of the desired effect
what drugs work on the CNS
cannabis and opiates
cocaine usage and half-life
- reaches peak in blood in blood at 30-60 mins
- half life of 30-90 mins
- easily penetrates blood-brain barrier
what does cocaine increase
- euphoria
- energy
- confidence
- talkative
- active
- attention
- alertness
mono-amines
- seratonin
- dopamine
- noradrenaline
- adrenalin
cocaine acts at the mono-aminergic synapse
