8/29 Neurobiology of Pain - Suss Flashcards
(32 cards)
sensory neuron fibers
A-alpha
type I
13-20 um
myelinated
receptors:
- muscle spindle : proprioception
- Golgi tendon organ : proprioception
sensory neuron fibers
A-beta
type II
6-12 um
myelinated
receptors:
- 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
A-delta
type III
1-5 um
myelinated
receptors:
- bare nerve ending : pain
- bare nerve ending : temp (cool)
- bare nerve ending : itch
sensory neuron fibers
C
type IV
0.2-1.5 um
UNmyelinated
receptors:
- 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
diabetes
- distal symmetrical polyneuropathy (glove and stocking)
- compromised microvasculature to nerve roots
- acute mononeuropathy
causes of sensory neuropathies
mechanical
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
diabetes
- 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)
sensitization
types
why?
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
why?
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
examples:
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
mechanisms:
- transcription independent (windup)
* lasts only during stimulation (acute) - 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)
