nociception

• Allodynia - Pain due to a stimulus that does not normally provoke pain. (brush against burnt skin)
• Hyperalgesia - Increased pain from a stimulus that normally provokes pain.
• Hypoalgesia - Diminished pain in response to a normally painful stimulus
• acute pain - seconds - prevents and reduces damage
• subchronic pain - hours - protective
• chronic/clinical - months or years
• nociceptors

  thermal - TRPV1, TEPV2 TRPV3 TREK-1

  acid - gated by protons TRPV1, ASIC, DRASIC

  mechano - MDEG, DRASIC, TREK-1

  cold - TRPM8
• primary afferent fibres

  • Aβ: Thick, myelinated, fastest

  Transmits: Light touch, pressure, vibration

  • Aδ - Medium, thinly myelinated, fast

  Transmits: Touch, temperature, & sharp pain

  • C: Thin, unmyelinated, slow

  Transmits: Noxious temperature, itch, pressure, & dull pain
• absence of input from c fibres (glutamate)

  • active inhibitory neurone supresses pain pathway

  strong pain

  • c fibre stops inhibition
  • strong signal sent to brain
• ascending pain pathway - spinothalamic tract - signals to thalamus

  • PAG & NRM send efferent signals down to the spinal cord, producing diffuse inhibition via inhibitory interneurons.
• descending pain pathways

  • PAG projects to the nucleus raphe magnus (NRM) and the rostral ventral medulla (RVM)
  • NRM & RVM send projections back down to the dorsal horn of the spinal cord
• inflammatory pain:

  • range of chemicals produced after tissue injury
  • lower pain threshold and sensitize nerve endings
  • Activation of nociceptors stimulates feedback systems that promote inflammation

  IMMUNE SYSTEM

  • Release of Substance P activates Mast Cells to release Histamine

  BLOOD VESSELS

  • Substance P and CGRP stimulate vasodilation & increase permeability of capillaries, facilitating inflammation
• COX-1, COX-2, COX-3 - causes inflammation and pain
• COX inhibitors - anti-inflammatory