05. Sensory Systems - Pain

• nociception = sensory portion of pain
• nociceptors have free nerve endings in the skin, muscle and viscera, no specialised apparatus
• mechanical nociceptor = cuts and blows, causes a sharp pain - A delta fibres

  • faster than C fibres, cause first pain showing localisation
• polymodal nociceptor = many stimuli, causing dull burning pain - C fibres

  • slower than A delta fibres causing second pain, showing strength of stimulus
• nociceptors synapse in the substantia gelatinosa in the spinal cord
• nociceptors are excitatory with glutamate as a neurotransmitter
• dorsal horn is mostly inhibitory interneurons - pain signal must overcome the inhibition
• nociceptors excite a inhibitory neurone which inhibits the normal inhibitory neurone leading to a pain signal being sent to the brain
• mechanoreceptor activation leads to less pain as it increases inhibition
• descending sensory pathways act as feedback control, releasing noradrenaline, serotonin and endogenous opioids to decrease pain
• hyperalgesia = heightened pain to normally painful stimuli
• allodynia = pain to no pain stimuli
• peripheral sensitisation:

  • antidromic action potentials lead to substance P and CGPR being released at the peripheral nerve ending
  • causes swelling and immune cell migration
  • causes release of pro-inflammatory substances
  • decreases threshold value leading to increased action potential generation
• central sensitisation:

  • low frequency firing leads to glutamate release which binds to AMPA receptor
  • high frequency ALSO leads to substance P release
  • this binds to NK-1 which further depolarises membrane
  • relieves Mg2+ block on NMDA, allowing for Ca2+ entry
  • Ca2+ leads to secondary messenger cascades