Nocioception I & II

Question 1

Types of temperature receptors (+fiber types)

Answer 1

• cool receptors (10-37°C)
  
  • 10x cool vs. warm
  • A(delta)
• warm receptors (30-48°C)
  
  • C fibers
• receptors turn temp info ==> receptor potential ==> action potential
  
  • frequency of APs indicates intesity
  • can indicate absolute temp and rate of temp change

Question 2

Anterolateral system tracts

Answer 2

• spinothalamic tract = conveys pain info to thalamus ==> somatosensory cortex
• spinoreticular tract = conveys pain inputs to forebrain arousal and emotion @ medulla and pons (reticular formation)
• spinomesencephalic tract = projects to periaqueductal gray region (PAG); desceding control of pain

Question 3

Anatomical pathway of pain/temp info

Answer 3

• (1°) pain or temp sensory receptor ==> sensory neuron ==> DRG ==> synapse @ dorsal horn
• (2°) dorsal horn ==> crosses midline @ anterior white commisure ==> ascends @ anterolateral tract ==> synapse @ thalamus
• (3°) thalamus ==> somatosensory cortex

Question 4

Pain and temp pathways for head/neck

Answer 4

• trigeminal ganglion neurons ==> enter @ pons ==> spinal trigeminal nucleus
• spinal trigeminal nucleus = ~ dorsal horn of spinal cord

Question 5

Types of pain receptors (+ fiber types)

Answer 5

• thermal nociceptors = activated @ extreme temps (<5ºC or >43ºC)
  
  • hot nociceptors = A(delta) fibers
  • cold nociceptors = C fibers
• mechanical nociceptors = activated @ intense pressure
  
  • A(delta) fibers
• polymodal nociceptors = activated @ high-intensity mechanical or thermal stimuli
  
  • C fibers

Question 6

Substance P characteristics

Answer 6

• neuropeptide transmitter @ pain afferents

Question 7

Vanilloid Receptor characteristics

Answer 7

• class of molecular components on nociceptors
• VR-1 = capsaicin receptor
  
  • strongly activated by capsaicin, weakly activated by acids
  • also activated by moderate heat
  • expressed on polymodal receptors
  • activation ==> NSC channel ==> depolarization

Question 8

Types of pain experienced in response to stimulus

Answer 8

• “first pain” = “pricking” pain
  
  • tolerable, localized
  • A(delta) fibers
• “second pain” = burning pain
  
  • uncomfortable, diffusely localized
  • C fibers

Question 9

Pain information carried by C fiber afferents

Answer 9

• “second pain”
• burning pain
• diffusely localized

Question 10

Characteristics/examples of pain activators

Answer 10

• compounds can lead to direct activation of nociceptors
• tissue damage ==> release of cytoplasmic proteases ==> bradykinin
  
  • activates A(delta) and C fibers
• potassium
• acid
  
  • activates ASICs (Acid-sensing) and VR-1
• serotonin

Question 11

Characteristics/examples of pain sensitizers

Answer 11

• agents that reduce the threshold for activation of nociceptors
• prostaglandins
• substance P
  
  • C fibers release during repetitive electrical stimulation
• ATP, ACh, serotonin
  
  • can act individually or together as sensitizers
• activators and sensitizers are likely to be present simultaneosly

Question 12

Asprin MOA

Answer 12

• Aspirin inhibits enzyme cyclooxygenase (COX)
• COX normall converts arachidonic acid to prostaglandin
• Aspirin inhibits prostaglandin formation ==> prevents nociceptor sensitization

Question 13

Characteristics of the triple response

Answer 13

• reddening, wheal, flare
• Tissue injury ==> bradykinin
  
  • ==> vasodilation ==> heat/redness
  • ==> increased capillary permeability ==> edema (wheal)
• flare = pinkish zone around inflammation
  
  • C fibers activated by bradykinin ==> APs towards cell body + collaterals and peripheral sites
  • ==> substance P release surrounding wound ==> some vasodilation (less than bradykinin)

Question 14

Site of first synapse in pain/temp pathway

Answer 14

• various regions of dorsal horn (aka “laminae”)
• C fiber afferents ==> Rexed lamina II = “substantia gelatinosa”
• second oder neuron has cell body in substantia gelatinosa

Question 15

Major NTs and receptors @ first synapse in pain/temp pathway

Answer 15

• Glutamate = major excitatory transmitter
• AMPA & NMDA receptors
  
  • both ionotropic
  • AMPA ==> rapid synaptic response
    
    • glutamate ==> open channel
  • NMDA ==> slower excitatory potential
    
    • require glutamate + depolarization before channels open

Question 16

Characteristics of “wind-up”

Answer 16

• “wind-up” = process of central sensitization
• C fibers stimulate ==> release glutamate ==> activate AMPA receptors first
• C fiber stimulation = intense + persistent ==> glutamate + post-synaptic depolarization ==> NMDA activated ==> larger post-synaptic response
• NMDA receptors become phosphorylated ==> removed requirement for depolarization for activation

Question 17

Substance P actions

Answer 17

• intense stimulation of C afferent fibers ==> released both @ periphery and centrally
• @ periphery ==> some vasodilation
• @ dorsal horn ==> binds receptor ==> close K⁺ channels ==> depolarization ==> enhancement and prolongation of actions of glutamate
  
  • _​_not removed by reuptake ==> persists and diffuses to many dorsal horn neurons ==> broad sensitization

Question 18

Analgesia definition

Answer 18

• inability to feel pain
• inhibition @ dorsal horn synapse

Question 19

Common method of inducing analgesia

Answer 19

• stimulation of A(beta) fibers ==> activation of dorsal horn interneurons ==> inhibit nociceptive synapses
• e.g. stroking/rubbing activates touch and A(beta) fibers
• e.g. transcutaneous electrical nerve stimulation (TENS) ==> stimulate A(beta) fibers @ injured area
  
  • in contrast: elimination of A(beta) inputs ==> hyperalgesia

Question 20

PAG (periaqueductal gray) region control of pain

Answer 20

• stimulation of PAG @ midbrain ==> powerful analgesic effect
• PAG neurons ==> medulla ==> medullary neurons use serotonin to excite an inhibitory interneuoron ==> endogenous opiates to reduce pain
  
  • reason for SSRI use in chronic pain
• PAG exposure to opiates ==> greater excitatory output from PAG

Question 21

Stress-induced analgesia characteristics

Answer 21

• = adaptive response to stressful conditions
  
  • e.g. soldiers/athletes unaware of injuries until situation calms
• stress ==> increased limbic activity ==> activation of PAG
• involves both opiod and nonopiod-mediated mechanisms

Question 22

Placebo effect characteristics

Answer 22

• administration of inert drug ==> alleviate sx or cures disease
• belief in drug ==> neocortex/limbic activity increase ==> PAG activation through increased endorphin secretion ==> analgesia

Question 23

Peripheral mechanisms of neuropathic pain

Answer 23

• spontaneous activity in primary sensory neurons ==> stimulus-independent pain conditions
• TTX-sensitive and TTX-resistant sodium channels contribute to normal and abnormal pain processing
  
  • nerve damage ==> alteration of distribution/fxn of sodium channels ==> spontaneous discharge
  • ==> tx w/sodium0channel blockers (CNS/cardio SEs)

Question 24

Central mechanisms of neuropathic pain

Answer 24

• nerve injury ==> reduced GABA/opiate receptors ==> decreased inhibition/increased excitability @ dorsal horn neurons
• nerve injury ==> A(beta) sprout and invade territory of substantia gelatinosa (normally only innervated by C fibers) ==> activated by non-noxious stimuli
• nerve injury ==> inflammation ==> help develop and maintain neuropathic pain