Pain physiology

  1. Physiology of nociceptive pain transmission
    1. Peripheral Transduction: nociceptor stimulation leads to generation of action potentials

    2. Transmission from the periphery to the CNS: the action potentials are conducted to the dorsal horn of the spinal cord by sensory afferent nerves (also referred to as primary(1°) afferents or 1st order neurons)

    3. Ascending modulation from the spinal cord to the brain: the peripheral afferent synapses onto cell bodies (referred to secondary neurons, or 2nd order neurons) that send axonal projections to the brain

    4. Brain awareness/perception: within the brain, the peripheral nociceptic stimuli is perceived as pain

    5. Descending modulation: axonal projections from neurons in the brain descend down the spinal cord and synapse onto cell bodies that transmit nociception from the periphery to the brain, thus, modulating the extent of ascending nociceptive input to the brain.
  2. Peripheral transduction @ nociceptor
    • chemical: bradykinin - vasodilator/inflammatory mediator, substance P - neurotransmitter that alters excitability of nociceptive afferents/proinflammatory
    • Thermal: activated > 43C
    • Mechanical: strong pressure
    • cell bodies of nociceptors located at DRG, trigeminal ganglia, nodose ganglia
  3. Types of peripheral nerve fibers
    • A-alpha and A-beta: large diameter, myelinated for motor and proprioception
    • A-gamma: smaller diameter, myelinated, for muscle tone
    • A-delta: smallest myelinated, ACUTE pain (A=acute), fast speed, pain, temp, touch
    • C: unmyelinated, chronic pain (C=chronic), slow speed, pain, temp, touch
  4. Transmission of peripheral fibers to spinal cord
    • gate control theory: input from A-beta fibers synapsing @ substantia gelatintosa (Rexed's lamina II) reduce effectiveness of nociceptive input of C fibers
    • neuromatrix theory: multidimensional experience - cognitive-evaluative, motivational-affective, sensory-discriminative
  5. sensitizaition factors
    • peripherally released sensitizing agents
    • enhancement of ionic flux in response to noxious stimuli
    • reduction of activation threshold of voltage-sensitive sodium channels
    • increase in second messenger/signal transduction pathways
    • changes in wide dynamic range neurons in DRG - respond to broad range of intensity of stimulation
    • NMDA receptors (not normally activated) now activated/"primed" b/c incr. [glu]
  6. capsaicin desensitization mech
    • due to depletion of substance P
    • massive accumulation of intracellular Ca++ -> destruction of cytoskeleton
    • mild swelling of the axons, possible terminal degeneration
    • not a local anesthetic, only blocks conduction of C fibers
  7. wide dynamic range neurons
    • increases in pain signals to these neurons increase their activity
    • A-beta activity can inhibit WDR neuron activity @ dorsal horn of spinal cord
Card Set
Pain physiology
pain wk2 blk4