Pharmacology of Pain Flashcards
How can pain occur within seconds to minutes?
Activation of nociceptive/specific wide dynamic range neurons proportional to intensity of stimulus
How can pain occur within minutes to days?
Sensitisation of nerve terminals at the injury site and delayed central sensitisation
How can pain occur within days to months?
Changes in supply of trophic growth factors, sprouting of fibres, abnormal innervation and trans-synaptic degeneration
What are the 3 types of pain?
- nociceptive (acute noxious mechanical/thermal/electrical stimuli)
- inflammatory (semi-acute or chronic ischaemia/infection/local degeneration)
- neuropathy (chronic maladaptive plasticity/disease affecting somatosensory nervous system)
What is the formation of the local circuits in the dorsal horn?
- first synapse between C fibre and dorsal neuron releases multiple transmitters which bind to various receptors
- NO, PG, glutamate
- interneuron modulates neuron so multitude of possible targets even just at first synpase
What is the role of opoids?
In the efferent pathway:
- activate PAG
- inhibits transmission directly at first synapse
- activates NRPG
- inhibits transmission at secondary neuron in periphery
Which parts of the brain do nociceptive stimuli activate?
- spinal cord
- thalamus
- somatosensory cortex
- anterior cingulate cortex
- insula
- amygdala
- prefrontal cortex
- hippocampus
What factors influence pain perception?
- cognition (attention/distraction/control/hypervigilance)
- mood (depression/anxiety)
- context (beliefs/expectations/placebo)
- chemical and structures (atrophy/dopaminergic dysfunction)
- injury (peripheral and central sensitisation)
- genetics
Which factors modulate the risk of developing chronic pain?
- hardware at birth (gender, genotype, epigenetic profile)
- environmental influences (acute injury/disease at critical developmental periods, stressful life events)
- gene + environment interactions (personality and psychology - pessimism/anxiety)
What are the 3 main families of opoids?
Proopiomelanocortin
Proenkephalin
Prodynorphin
What are the main receptors which opoids act on?
- Mu (1 and 2, widespread)
- Delta (1 and 2)
- Kappa (1,2,3)
- also pro-nociceptive endogenous systems such as CCK
What explains the broad spectrum of effects of opoids?
- Mu receptors being widely distributed
What are the problems of direct administration of opoids?
Very short half-lives so rapidly inactivated in circulation
Why can Mu receptors be negative?
- when opoids bind react most intensely which can cause adverse effects:
- increased dependence, respiratory depression, pupillary constriction
How can receptors to opoids be targeted in different patients?
- cause difference is responses
What are the 3 types of analgesia?
Supraspinal
Spinal
Peripheral
Which opoid receptors cause supraspinal analgesia?
Mu receptors
Which opoid receptors cause spinal analgesia?
Mu receptors
Delta receptors
Kappa receptors may
Which opoid receptors cause peripheral analgesia?
Mu receptors
Kappa receptors
Which opoid receptors cause pupillary depression?
Mu receptors highly
Delta receptors
Kappa receptors may
Which opoid receptors cause pupillary constriction?
Mu
Which opoid receptors cause reduced GI motility?
Mu
Delta
kappa may
Which opoid receptors cause sedation?
Mu
Kappa
Which opoid receptors cause euphoria?
Mu
