Pain management

• What is pain?

  an unpleasant sensory and emotional experience associated with actual or potential tissue damage
• Pain is multifactorial and many aspects can modulate the level

  • injury
  • infection
  • inflammation
  • gender
  • age culture
  • expectation
  • hospitalisation
  • anxiety
  • stress
• positive effects of pain

  • danger alert
  • withdrawal
  • protection
  • rest injury
  • prevention
  • learning
• negative effects of pain

  • suffering
  • impaired function
  • motor
  • respiratory
  • CVS

  Relieving pain hopes to alleviate all these
• pain pathway

  • pain recognition
  • peripheral conduction
  • spinal processing
  • ascending transmission
  • relay to cortex
• Nociceptors are bare nerve endings

  • mostly in skin
  • some in deeper tissues
  • some dormant - activated by injury
• Nociceptors respond to several stimuli

  • mechanical, thermal, chemical
• Nociceptors are sensitised by inflammatory mediators

  • bradykinin, histamine, prostaglandins
• fast response pain conduction

  • a-delta fibres
  • large, myelinated
  • up to 10 m/sec
  • sharp, stabbing pain
• slow response pain conduction

  • C fibres
  • small, unmyelinated
  • 1.2 m/sec
  • aching, burning pain
• spinal transmission of pain

  • dorsal root ganglion
  • lateral spinothalamic tract
• withdrawal reflex

  • synapses in dorsal root ganglion
  • interneurone to anterior horn cell
  • synapse then to muscle fibre
• Visceral pain is initiated by distension, inflammation or ischaemia
• visceral pain pathways are generally via autonomic nerves and poorly localised
• visceral pain may be perceived in the relevant dermatome -referred pain
• Cardiac pain localises to central chest/arm (T1-T4)
• uterine pain localises to low central abdomen (T10-T12)
• neuropathic pain results from nerve damage

  • trauma
  • infection e.g. herpes zoster
  • often becomes chronic
  • difficult to treat
• analgesic strategy targets pain pathway between pain recognition and relay to cortex
• Analgesic strategy can involve physiological pain modulation

  • amplification systems
  • inhibitory systems
• NSAIDs target amplification systems
• Opioids/SRI target inhibitory systems
• local anaesthetics target pain pathways
• Local anaesthetics overall structure

  • aromatic ring (lipophilic)
  • amide or ester link
  • amine group (hydrophilic)
• local anaesthetics are bases - proton acceptors
• charged form of amine group (quaternary ammonium group) important for function of local anaesthetics
• • local anaesthetic administered extracellularly in ionised form
  • becomes unionised to cross membrane
  • works intracellularly in ionised form to prevent Na+ channels opening
• first local anaesthetic was cocaine
• ester local anaesthetics have now largely been replaced by less toxic amides

  • lidocaine (short acting)
  • bupivacaine (long acting)
• Local anaesthetics

  • very effective short-term for specific target sites (epidural, intercostal, brachial plexus etc.)
  • drugs are dangerous - must be monitored appropriately
• prostaglandins are part of the eicosanoid system

  • local cell signalling
  • derivates of eicosanoic acid
• prostaglandins are short-lived

  • synthesised and released almost instantly
• prostaglandins are involved in many actions, including peripheral pain sensitisation - PGE2
• prostaglanding synthesis

  • phospholipid
  • arachadonic acid
  • leukotrienes
  • prostaglandin H2
  • thromboxanes
  • prostaglandins
• PGE2

  • pain sensitisation
  • renal arteriole
  • dilatation
  • ductus arteriosus patency
• PGF2a

  • bronchoconstriction
  • uterine contraction
• PGI2

  • inhibition of platelet aggregation
  • vasodilatation
• TXA2

  • activation of platelet aggregation
  • vasoconstriction
• COX-2

  • constitutive (background)
  • gastric protection
  • platelet aggregation
  • renal protection
• COX-2

  • inducible (responsive)
  • inflammation
  • hyperalgesia