Nocioception I & II Flashcards
Types of temperature receptors (+fiber types)
- 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
Anterolateral system tracts
- 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
Anatomical pathway of pain/temp info
- (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
Pain and temp pathways for head/neck
- trigeminal ganglion neurons ==> enter @ pons ==> spinal trigeminal nucleus
- spinal trigeminal nucleus = ~ dorsal horn of spinal cord
Types of pain receptors (+ fiber types)
- 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
Substance P characteristics
- neuropeptide transmitter @ pain afferents
Vanilloid Receptor characteristics
- 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
Types of pain experienced in response to stimulus
- “first pain” = “pricking” pain
- tolerable, localized
- A(delta) fibers
- “second pain” = burning pain
- uncomfortable, diffusely localized
- C fibers
Pain information carried by C fiber afferents
- “second pain”
- burning pain
- diffusely localized
Characteristics/examples of pain activators
- 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
Characteristics/examples of pain sensitizers
- 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
Asprin MOA
- Aspirin inhibits enzyme cyclooxygenase (COX)
- COX normall converts arachidonic acid to prostaglandin
- Aspirin inhibits prostaglandin formation ==> prevents nociceptor sensitization
Characteristics of the triple response
- 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)
Site of first synapse in pain/temp pathway
- various regions of dorsal horn (aka “laminae”)
- C fiber afferents ==> Rexed lamina II = “substantia gelatinosa”
- second oder neuron has cell body in substantia gelatinosa
Major NTs and receptors @ first synapse in pain/temp pathway
- 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
Characteristics of “wind-up”
- “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
Substance P actions
- 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
Analgesia definition
- inability to feel pain
- inhibition @ dorsal horn synapse
Common method of inducing analgesia
- 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
PAG (periaqueductal gray) region control of pain
- 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
Stress-induced analgesia characteristics
- = 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
Placebo effect characteristics
- administration of inert drug ==> alleviate sx or cures disease
- belief in drug ==> neocortex/limbic activity increase ==> PAG activation through increased endorphin secretion ==> analgesia
Peripheral mechanisms of neuropathic pain
- 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)
Central mechanisms of neuropathic pain
- 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