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Pathophysiology of Pain (Nociceptors (What are they? (specialized sensory…

- - - - selectively respond to noxious or potentially tissue-damaging stimuli
        
        thermal
        
        mechanical (pressure)
        
        chemical (e.g. K+ or H+ ions_
    - - Important property: can be SENSITIZED
        
        their excitability can be increased as a result of tissue damage and inflammation
        
        Sensitization + a reduction in the threshold at which the nociceptor responds to a noxious stimulus and an increase in the magnitude of that response
  - - - well-localized
      - originates from receptors in skin, muscles, joints, or bones
    - - when internal organs swell, stretch, or become damaged
      - poorly localized
  - - - direct stim. of afferent neurons due to tissue injury, or stimuli indicating potential injury or tumor infiltration of skin, soft tissue, or viscera
    - - 1) Transduction
        
        process of converting painful stimuli to neuronal action potentials, nociceptors transduce noxious stimuli into action potentials and are sensitized
        
        chemical mediators alter the membrane potential of the nociceptor --> increased sensitivity (and reactivity) of nociceptor to noxious stimuli
        
        once released, these chemicals -bind and activate spec. receptors on the nociceptor -increase the excitability of neuronal cell membrane -lead to gen. of an AP
        
        chemical mediators released include K+, H+, serotonin, bradykinins, NE, prostaglandins, others
      - 2) Transmission
        
        stim. nociceptors transmit impulses to the CNS by means of specialized sensory fibers
        
        A8 fibers: large, myelinated fibers involved in fast transmission of sharp, stinging, and highly localized pain
        
        C fibers: small, unmyelinated fibers involved in slower transmission of dull, aching, and poorly localized pain that lingers
        
        Most sensory afferent pain fibers enter the spinal cord by way of the posterior nerve roots
        Cell bodies of pain neurons located in the dorsal root ganglion of the spine.
        
        Pain signals transmitted by afferent fibers enter the spinal cord through the dorsal horn, synapse on second order neurons, and then cross the cord (decussate) and project centrally in the anterolateral tract
        
        Neurotransmitters that bind N-methyl-D-aspartate (NMDA), AMPA receptors in spinal cord are released.
        
        Signal terminates in thalamus, which acts as relay station to cortical regions.
      - 3) Perception
        
        Impulse becomes a conscious perception of pain
        
        Pain threshold - level of pain stimulation required ot be percieved
        
        degree of pain and individual is willing to bear before seeking relief
        
        Likely brain structures involved:
        
        Somatosensory cortex - localization and interpretation/characterization
        
        Limbic system - emotional and behavioral
        
        Reticular system - autonomic response
      - 4) Modulation
        
        descending pathway from the brain to the dorsal horn of the spine
        complex mechanism whereby synaptic transmission of pain signals is changed
        
        may be inhibited or amplified
        
        Key players in inhibiting pain signals
        
        endogenous opioids - block release of NT
        
        serotonin
        
        norepinephrine
        
        GABA
        
        Rub it, it will feel better! Activates A-beta fibers which inhibit transmission of nociceptive info (Gate Control Theory)
- - - - Although the pain feels as if it originates in the periphery, it is actually a manifestation of abnormal sensory processing within the CNS.
        
        can persist long after healing of the injury in chronic pain states - maladaptive
        
        may result from inadequately-treated pain
- - - - nerve regeneration results in sprouts and neuromas that fire spont.
      - peaks several weeks after injury
      - change in expression of Na/K channels
    - - low-threshold sensory fibers terminate in areas where nociceptive neurons usually terminate
      - assc. allodynia and hyperalgesia
  - - - post stroke pain, pain assc. with MS or Parkinson's, spinal cord injruy
    - - post-herpetic neuralgia, diabetic neuropathy, chemo-induced neuropathy, HIV sensory neuropathy, phantom limb pain