Pain pathway
Nociception -> pain -> suffering -> pain behaviour
3 sources of pain
- trauma
- inflammation
- ischaemia
Physiology of trauma
Neuronal - free nerve endings
Conducted by A delta fibres
Myelinated - fast pain, quick reaction
Physiology of ischaemia and inflammation
Chemical - prostaglandins/histamine
Conducted by C fibres
Unmyelinated - delayed and continued pain
Gate control theory
Pain conduction is modulated at the spinal cord by peripheral nerve impulses and impulses from the brain
Gate-closing stimuli
Peripheral nerve stimulation (rubbing)
Mental state: endorphins, dynorphins and enkaphalins bind to ion-gated channels of post-synaptic nerve
Gate-opening stimuli
Glutamate (most excitatory neurotransmitter) binds to receptors
Mental stress (lack of feel good chemicals)
Bradykinin and other inflammatory mediators
Inflammation is caused by… in order to…
tissue damage
minimise consequences of damage and start repair
Symptoms of inflammation (5)
Redness Swelling Heat Pain Loss of function
3 stages of inflammation
- Damage to blood vessel: compromises laminar blood flow, so cells start hitting endothelium on inside of vessel
- Change in vascular permeability: joints in cell start leaking plasma and proteins, causing a drop in oncotic pressure and more fluid in interstial area
- Leukocyte accumulation: leukocytes migrate and adhere to side of blood vessel, opening gaps between cells further so they can emigrate to damaged area
- Phagocytosis of bacteria and damaged tissue and release of leukocyte product which dissolves foreign body
Biochemical process of inflammation
- Phospholipid from bilayer is acted on by phospholipase A2
- Creates arachidonic acid
- 5-lipoxygenase turns arachidonic acid into leukotrins, which attract white blood cells, cause vasoconstriction, bronchoconstriction, and vascular permeability
- Cycloxygenase 1+2 turn arachidonic acid into prostaglandins, anticoagulants, and platelet activator
Causes of ischaemic pain
Spasm causes blocked or narrowed blood vessels
O2 starvation
Process of ischaemic pain
- O2 starvation causes a lack of ATP
- Cells generate energy anaerobically
- Increased lactic acid
- Increase in hydrogen ions
- Increased acidity is perceived by pH sensitive nerves, which is converted to pain
Acute pain
Less than 3 months
Response to a natural or therapeutic process
Response to trauma
Chronic pain
More than 3 months
Typically not ‘useful’
Often caused by degeneration
Mechanism of local anaesthetics
Stop nerve conduction by preventing sodium ion channels working
Adverse effects of local anaesthetics (5)
Neurological disorders Convulsion Restlessness Respiratory paralysis Cardiac disorders - reduced impulse conduction
2 areas of pain relief
Epidural - between dura matter and vertebral spines
Spinal block - next to spinal cord
Mechanism of opioids
- Mimic endorphins, dynorphins and enkaphalins
- Bind to receptor on pre-ganglionc nerve
- Prevent neurotransmitter release by opening K+ channels
- Prevents depolarisation
Adverse effects of opioids (10)
Cough centre depression Sweating Pupil constriction Euphoria Respiratory depression Bronchial contraction Vasodilation Biliary spasm Decreased peristalisis (constipation) Increased bladder tone
Types of opioid
Morphine
Codeine (less potent)
Pethidine (doesn’t cause constriction of smooth muscle, but is metabolised quickly)
Tramadol (synthetic)
PK/PD lag
With opioids, the effect of drug is felt after drug levels have peaked, not at peak
Non-opioid analgesics (2)
- Non-steroidal anti-inflammatory drugs (NSAIDs), e.g. paracetamol or ibuprofen, inhibit cycloxygenase to reduce swelling and pressure
- Corticosteroids stop formation of arychonic acid from phospholipid
