Pain

• What is the research area of Rory Mitchell in physiology?

  Cellular and molecular mediators of pain processing
• What are the novel molecular targets for analgesia mentioned in the study material?

  Novel molecular targets for analgesia
• What is nociception?

  Processing of noxious sensory inputs
• What type of neurons are sensory neurons in the context of pain?

  Bipolar, with cell bodies in dorsal root ganglia
• What do nociceptors respond to?

  Intense mechanical, thermal, or chemical stimuli
• What are the types of sensory nerve endings in the skin?

  Nociceptors
• What are the characteristics of A$b$ fibers?


  Thickly myelinated axons with fast conduction
• What are the characteristics of A$d$ fibers?


  Thinly myelinated axons with slower conduction
• What are the characteristics of C fibers?

  Unmyelinated axons with very slow conduction
• What are the subtypes of afferent neurons in pain processing?

  • Primary sensory neurons relay in spinal dorsal horn
  • First relay occurs in the dorsal horn of the spinal cord
  • Nociceptive and non-nociceptive afferents terminate in different laminae
• Where do nociceptors terminate in the dorsal horn?

  Laminae I, II, V
• Where do non-nociceptors terminate in the dorsal horn?

  Laminae III, IV
• What are the two major classes of C-fiber nociceptors?

  • Peptidergic: express Substance P / CGRP
  • Non-peptidergic: bind IB4 lectin
• What role do interneurons in the superficial dorsal horn play?

  They can modulate pain inputs before relay to the brain
• What is the spinothalamic tract responsible for?

  Somatosensory pathway through thalamus to somatosensory cortex
• What is the spinoparabrachial tract responsible for?

  Affective pathway through brainstem to hypothalamus and amygdala
• What does fMRI scanning reveal about pain?

  Multiple regions of the brain are activated by noxious stimuli
• What is meant by "endogenous analgesia"?

  It refers to the body's natural pain relief mechanisms
• What was the prevalence of back pain in Scotland in 2010?

  8%
• What are the impacts of chronic pain on quality of life?

  • Difficulty sleeping: 60%
  • Lack of energy: 55%
  • Drowsiness: 39%
  • Poor concentration: 36%
  • Depression: 33%
  • Anxiety: 27%
  • Lack of appetite: 18%
• What are the classifications of chronic pain states?

  • Inflammatory: trauma, infections, arthritis, post-operative, colitis
  • Neuropathic: surgery, amputations, traumatic plexus avulsions, peripheral neuropathies, trigeminal neuralgia, central pain
• What is the treatment for inflammatory pain?

  Opioids and NSAIDs, which are effective
• What is the treatment for neuropathic pain?

  It is difficult to treat
• What is allodynia?

  When innocuous stimuli evoke pain
• What is hyperalgesia?

  When pain is worse and stimuli that are normally innocuous can evoke pain
• What causes chronic hypersensitive pain states?

  • Increased excitability of sensory nerves (peripheral sensitisation)
  • Changes in the spinal cord (central sensitisation)
• What is peripheral sensitisation?

  Marked sensitisation of peripheral nociceptor terminals due to inflammatory mediators
• What happens during central sensitisation?

  Persistent noxious stimuli evoke lasting increases in spinal neuron excitability
• What role does glutamate play in central sensitisation?

  It contributes importantly to central sensitisation via the NMDA receptor
• What are the functional changes in chronic hypersensitive pain states?

  Increased excitability of neurons in the dorsal horn
• What are spontaneous electrical discharges in afferent nerves associated with?

  They contribute to sensitisation
• What changes occur in afferent gene expression profile due to nerve injury?

  Marked phenotypic changes in mRNAs in DRG cells
• What are examples of neuropathic pain?

  • Diabetic neuropathy
  • Post-herpetic neuralgia
• What is the efficacy of current analgesics in neuropathic pain states?

  They show very poor efficacy and dose-limiting side effects
• What is the estimated number of patients with diabetic neuropathy worldwide by 2035?

  Approximately 300 million
• What percentage of patients with post-herpetic neuralgia have profound mechanical hypersensitivity?

  Up to 80%
• What are the references cited in the study material?

  • Basbaum AI, Woolf CJ. (1999) Pain. Curr Biol. 9:R429-31.
  • Woolf CJ, Salter MW. (2000) Neuronal plasticity: increasing the gain in pain. Science 288:1765-8.
  • Basbaum, Bautista et al. (2009) Cellular and molecular mechanisms of pain. Cell 139:267-84.