8/29 Neurobiology of Pain - Suss Flashcards Preview

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Flashcards in 8/29 Neurobiology of Pain - Suss Deck (32)

sensory neuron fibers



type I

13-20 um




  • muscle spindle : proprioception
  • Golgi tendon organ : proprioception


sensory neuron fibers



type II

6-12 um




  • muscle spindle : proprioception
  • Meissner's corpuscle : superficial touch
  • Merkel's receptor : superficial touch
  • Pacinian corpuscle : deep touch, vibration
  • Ruffini ending : deep touch, vibration
  • hair receptor : touch, vibration


sensory neuron fibers



type III

1-5 um




  • bare nerve ending : pain
  • bare nerve ending : temp (cool)
  • bare nerve ending : itch



sensory neuron fibers



type IV

0.2-1.5 um




  • bare nerve ending : pain
  • bare nerve ending : temp (warm)
  • bare nerve ending : itch



nociception involved SPECIALIZED neurons and receptors

ex. temp sensation - thermoreceptors sense up to a certain point, nociceptors take over after that point


  • nonnociceptive thermoreceptors continue to respond at same rate even at higher temps
  • nociceptors respond at higher temps only


pain temporal elements


which fiber conducts?

first pain : A-delta fiber

second pain : C fiber


four components of pain

1. sensory discriminative component (who/what/when)

  • location, intensity, quality of stimulation
  • depends on pathways that target traditional somatosensory areas of cortex

2. affective motivational component

  • unpleasant quality of experience that activates autonomic nervous system
  • depends on addtl cortical and brainstem pathways

3. sensitization

  • hypersensitivity to protect injured area, promote healing, prevent infection

4. descending control/central modulation

  • reduce pain perception


anterolateral pathways that transmit nociceptive information

1. spinothalamic tract : discriminative aspects of pain, temperature

  • facts of what's causing pain

2. spinoreticular tract : emotional and arousal aspects of pain

  • emotional aspects of pain (sweat, fear, desire for comfort)

3. spinomesencephalic tract : central modulation of pain

  • descending control of pain that helps reduce pain sensation


anterolateral pathways

starting in rostral medulla

  • STT continues up into thalamus
  • SRT sends axonal projection to reticular formation in pons
  • SMT sends projections to superior colliculus (bump in midbrain) and periaqueductal gray


also anterolateral projections to midline thalamic nuclei → cingulate cortex + insular cortex


thalamic relays of somatosensory system

VPL : medial lemniscus, spinothalamic tract

VPM : trigeminal lemniscus, trigeminothalamic tract


midline thalamic nuclei : spinoreticular & spinomesencephalic tracts

intralaminal nuclei : spinoreticular & spinomesencephalic tracts


chronic pain and gray matter

chronic pain can decrease gray matter


localization of lesions : paresthesia


lesion of parietal lobe or primary sensory cortex

contralateral numb tingling or pain


localization of lesions : paresthesia


lesion of thalamus

contralateral burning pain 

[Dejerine-Roussy Thalamic/Central Syndrome]


localization of lesions : paresthesia


lesion of DCMLS

  • tingling, numb sensation
  • tight band-like sensation around trunk or limbs
  • feeling of having gauze on fingers
  • electric sensation down back/extremities upon neck flexion [Lhermitte's sign]


localization of lesions : paresthesia


lesion of nerve roots

radicular pain with numbness and tingling in dermatomal distribution [radiculopathy]


localization of lesions : paresthesia


lesion of anterolateral STT pathways

sharp, burning, or searing pain


causes of sensory neuropathies



  • distal symmetrical polyneuropathy (glove and stocking)
    • compromised microvasculature to nerve roots
  • acute mononeuropathy


causes of sensory neuropathies



extrinsic compression, traction, laceration, or intrinsic entrapment

  • neurapraxia : mild insult [temp impairment of nerve conduction]
  • Wallerian degen : severe insult [degen distal to site of injury; regen may occur]
  • causalgia/complex regional pain syndrome : incomplete regen → burning sensation, edema
  • neuralgia : severe persistent pain in distributino of CN or spinal nerve
    • ex. trigeminal neuralgia


causes of sensory neuropathies



  • distal symmetrical polyneuropathy (glove and stocking)
    • compromised microvasculature to nerve roots
  • acute mononeuropathy


causes of sensory neuropathies


Varicella/Herpes-zoster virus

increases excitability of sensory neurons in DRG → low threshold of firing and spontaneous activity

ex. shingles → severe pain in dermatomal distribution/rash

tx: antivirals


Na channel mutations and pain sensation


which gene

how they found it

diff types of mutations in it

congenital insensitivity to pain in family in Pakistan → research has revealed the gene responsible 


Na v1.7 encoded by SCN9A gene

  • recessive mutations → loss of function →
    • congenital insensitivity to pain (CIP)
  • dominant mutations → gain of function
    • inherited erythromelalgia (IEM) : extreme sensitivity to temp
    • paroxysmal extreme pain disorder (PEPD)






repeated application of noxious stimulus leads neighboring neurons that were NOT responsive to become responsive!

  • hyperalgesia : phenomenon of stimuli that are normally perceived as slightly painful → significantly more painful
  • allodynia : induction of pain by what is normally an innocuous stimulus


protects injured area, promotes healing, prevents infection

results from changes in sensitivity of peripheral nociceptive receptors and/or central targets


peripheral sensitization

sensitization of first order (DRG) neuron


result of interaction of nociceptors with substances in "inflammatory soup" → decrease threshold of activation for nociceptors


Substance P → vasodilation of blood vessels (edema), degranulation of mast cells → histamine released (lowers threshold of DRG neuron activation)

prostaglandins : increase response of nociceptive fibers

  • application: NSAIDs (ex. aspirin, ibuprofen) fx by inhibiting COX to prevent synthesis of prostaglandins!


central sensitization

sensitization of CNS neuron (second order neuron)


immediate, activity-dep increase in excitability of neurons in dorsal horn of spinal cord following high levels of activity in nociceptive afferents to increase pain sensitivity



1. transcription independent (windup)

  • lasts only during stimulation (acute)

2. transcription dependent (allodynia) 

  • can outlast stimulus for hours (chronic)
  • can be mediated by COX 


  • devpt of or increase in spontaneous activity
  • reduction in threshold for activation by peripheral stimuli
  • expansion of receptive field size (conversion of cociceptive-specific neurons → wide dynamic neurons that can response to both innocuous and noxious stimuli)


capsaicin as analgesic

moderate heat and capsaicin activate

  • vanilloid receptor (VR1) in C fibers
  • transient receptor potential (TRPV1) in C fibers

repeated application of capsaicin...

  • causes desensitization of C fibers → blocks peripheral sensitization!
    • how? continuous activation causing them to run out of nt!
  • depletes Substance P → blocks peripheral sensitization!


descending control of pain perception

1. stress-induced analgesia

  • battlefield/athletic injuries often don't present until AFTER stressful situation 
    • fight or flight response is overriding pain perception

2. placebo effect : physiological response following admin of a pharmocologically inert "remedy"

  • effects can be blocked by naloxone (inhibitor of opiate receptors)
  • may explain hypnosis, meditation, acupuncture, mother's kiss


overlap in brain activation: 


pain & meditation

  • anterior cingulate cortex
  • insula


both areas are triggered by both pain and meditation


how do endogenous opioids work to reduce pain perception?

enkephalins, endorphins, dynorphins affect descending control of nociceptive info


descending inputs through downward projections (ex. Raphe nuclei) synapse on enkephalin-containing local circuit neuron (interneuron) → INHIBITS the signal of the C fiber (nociceptor) onto the dorsal horn projection neuron


gate theory of pain


what is it?

example of the stubbed toe

  • players at work, what they do

application of theory

local modulation of nociceptive information


  • pain results from the balance of activity in nociceptive and non-nociceptive afferents

implication : when you stub your toe...

  • PAIN RELAY: activation of C fibers → hit secondary dorsal horn neuron with pain signal + inhibit inhibitory interneuron (so as to open the gates to pain reception)
  • RUBBING YOUR TOE: activation of mechanoreceptors (A-beta fibers) → activate inhibitory interneurons to MODULATE the transmission of pain (close the gates a little)!

application : TENS (transcutaneous electrical nerve stimulation) activates A-beta fibers → reduces pain


dorsal column pathway for visceral pain

pain signal on primary neuron hits DRG cells and synapses close to midline

secondary neuron ascends in dorsal column pathway

  • DOES NOT decussate right away!
  • instead, moves ipsilaterally up to medulla before second synapse

tertiary neuron decussates in medulla → heads up to ventral posterior thalamus to third synapse

quarternary neuron sends signal out to insula


surgical interventions for intractable pain

1. midline myelotomy for visceral pain

  • selective cutting out of transmission areas

2. cordotomy for cutaneous pain

  • cut lateral funiculus from dentate ligament to line of ventral rootlets several segments rostral to highest dermatomal level of pain


referred pain

visceral pain that is conveyed centrally by neurons that carry cutaneous pain


when multiple primary order neurons converge on same secondary order neuron, you cannot distinguish which "primary site" the pain originated at

→→→ referred pain!

ex. esophagus and heart have overlap → GERD can present as pain on L ant chest wall, so you get mixup between MI and GERD

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