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Which nerve fibers are the largest in the dental pulp?
Aβ are larger than Aδ and C fibers
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Nerve fibers contribute to tooth survival by (3 sub 3)
- 1. Detecting stimuli
- 2. Dental reflexes
- 3. Interacting w/ OD, Fibroblasts, BVs, immune
All this to protect, maintain healthy function and repair
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Tooth nerves can be classified based on:
- 1. Sensory perception (sharp, dull, prepain)
- 2. Effective stimulus (mechanical, thermal, chemical, noxious, polymodal)
- 3. Conductive velocity (Aβ, Aδ-fast, Aδ-slow, C and C Sympathetic)
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Where to terminal sympathetic fiber have their cell bodies?
Cervical sympathetic ganglion
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What is the rate of transport of vesicles anterograde and retro grade of neurons?
1-400mm/day peripheral and central anterograde (towards the cell body)
50-100mm/day retrograde (away from cell body)
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The nerve fibers of the pulp are part of a somatosensory system that includes:
Gingiva, junctional epi, PDL, Tongue, Lips, masticatory, TMJ
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Where do most A fibers terminate?
Coronal OD layer, predentin, and inner
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Where do most C fibers have their terminals?
Deeper in pulp along BVs
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Aβ fibers make large endings near:
ODs (close) along dentin-pulp border near horn tip
Lack receptors for NGF
Most sensitive to hydrodynamic stimulation of dentin
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Majority of A fibers are _____ and ________ myelinated fibers.
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What neuropeptide do A fibers contain?
CGRP and express receptors for NGF (except Abeta)
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Where is most of the Aδ innervation concentrated?
Dentin near the pulp horn tip and less freq toward cervical region, least in root dentin
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Two types of Aδ fibers?
Fast conducting
Slow conducting: sensitive to capsaicin, thin
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At least half of the nerve fibers in human teeth are ___________, slow-conducting __ fibers
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The GDNF (glial cell line derived neurotrophic factor) dependent group of fibers have this function
Mechanosensitive
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NGF dependent fibers have this function
polymodal or nociceptive sensitivity, as well as paracrine signaling
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All fibers in the pulp continue to express this protein
GAP-43, growth assoc protein
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Sympathetic fibers are located where in the pulp
deeper pulp and along BVs
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How do we know that ODs do not have a primary sensory function?
they lack synaptic and gap junctions with nerve fibers
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What indicates that ODs are excitable and mechanosensitive?
Neural like ion channels and TREK-1 (mechanosensitive potassium channel)
Attract nerve fibers
Express neurotrophin factors and receptors
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How do fibers convey info about pulp status to the cell body?
Pick up and transport local pulp factors such as NGF
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Type 1 Injuries
- Least damaging
- 1. transient change
- 2. Reactive dentinogenesis
- 3. sprouting of neuropeptide-rich nerve fiber endings (return to normal days-weeks)
- 4. Little/no invasion of leukocytes
Example: shallow cavity, scaling, strong ortho
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Type II injuries
- Extensive dentinal injury
- 1. loss of pulp tissue
- 2. invasion of leukocyctes, local vascular resp
- 3. reparative dentin
- 4. ext sprouting, CGRP and subst P contents continues until walled off by scar (old folks able to as well)
Example: deep cavity, small pulp exp, heat stimulation
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Type III injuries
- Pulpal damage that cannot be repaired
- 1. IP insues
- 2. intense nerve sprouting, inc NFG expression
Examples: infect pulp exp, bacterial invasion from leaked restoration, deep infected caries, failure of scar around abscess
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Type IV injuries
- involve other tissues, out of the radicular structure
- 1. PDL involved
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What are the typical responses to fiber sensory endings in brainstem and ganglion during inflammation?
1. altered exp of neurotrophin receptors, neuropeptides, voltage ion channels
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c-Fos and tooth injuries?
Injuries cause persistent expression, indicates altered central pain pathway functions
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Difference between adult and primary teeth in density of innervation?
Coronal regionas are more innervated than radicular in both BUT
in primary teeth cervical third of the coronal region more dense than adult (less dentinal tubules in kids innervation)
less CGRP, subst P, and VIP
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Sharp increase in sensitivity is seen when the ____ _____ of teeth _____.
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Name the neuropeptides located in the pulpal axons
- Tachykinins
- Neurokinin A and SP
- CGRP
- VIP
- NPY
- Cholecystokinin
- Somatostatin
- Galanin
- Methionine
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How do CGRP and SP function in neurogenic inflammation?
- 1. Blood flow control
- 2. Inflammation
- 3. Tissue repair
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Which neuropeptides produce vasodilation and which one vasoconstriction?
VD: CGRP, SP, NKA, VIP
VC: NPY (inhibits SP release by sympathetics)
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Which neuropeptides are anti-inflammatory?
NPY (vasoconstrictor and inhibits SP release)
VIP (though vasodilatory it inhibits pro-inflammatory cytokines while upregulating anti-inf IL-10)
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Which cytokines do CGRP and SP promote?
TNF-alpha, IL1-beta, IL-6
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Upregulation of SP and CGRP receptors occurs as a gradient because expressions are _______ in pulp tissues with ________ _________ and presence of _________ to _________ ________
- highest
- irreversible pulpitis
- moderate
- severe pain
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Pulp expression of NPY varies in caries infected teeth how?
Most expressed in mild to moderate caries
Least in severe caries and even less in normal pulps
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The effect of most neuropeptides is controlled by which protein receptor?
GPCR (g-protein coupled receptors)
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Somatostatin and NPY are linked to which g-protein pathway?
G-alphai/o GPCR pathway
Inhibitory pathway of nerve activity (analgesic effect wiht opoids working this way too)
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Which GPCRs excite nerve activity?
- Galphas GPCR increase
- Prostaglandins and CGRP work here
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Which GPCR pathways causes increased pain levels?
Galphaq GPCR pathway
Activated by SP, bradykinin, endothelin
lead to Phospholipase-C and protein Kinase C activation on nociceptors
sensitization of TRPV1 receptors
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What is the capsaicin receptor?
TRPV1
temp activated activity (more than 43C)
active at lower temps with inflammatory mediators
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What Na channels are most likely involved in in pulpal pain mechanisms?
Na 1.7, -1.8, and -1.9
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What is temporal summation?
inc of the electrical stimulation freq of low intensity changes the nonpainful (prepain) sensation to a painful one
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Studies indicate there is a _____ correlation between clinical ____ symptoms and the ________________ status of the pulp.
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Classification of the pulpal primary afferents as A and C fibers is based on
their conduction velocities
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Slow A-delta are sensitive to ________, where as most fast A-delta fibers respond to _________ stimulation
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C fibers do not respond to dentinal __________ stimulation, the sensitivity of dentin is entirely based on the function of intradental _ fibers
hydrodynamic
A
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What is variation in pain quality attributed to?
Activation of diff nerve fiber types and diff in the nerve firing patterns evoked by various stimuli
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What fiber groups are involved in the mediation of prepain?
ABeta and Adelta fibers
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Basis of single-fiber recordings activation of a _____ number of pulpal afferents is needed to evoke prepain or pain. Significance?
Small
Produce false-positive response, even in extensive pulpal necrosis, as long as some axons are still responsive
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What mediates the intradental nerve activation in response to several different stimuli from all experiments taken together?
Hydrodynamic mechanism
Responding fibers are Adelta and ABeta
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Pulpal _ fibers are ___________ because they respond to several different modes of stimulation and have high thresholds for activation.
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The ____ pain induced by pulpitis may be evoked by C-fiber activation.
dull
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________ of the dentinal tubules is required for the ____________ of exposed dentin.
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Name the six types of sensory axon
- 3 A fibers (myelinated)
- 1. Aβ : large, fastest (30-70m/s)
- 2. Adeltaf: medium fast (12-30m/s)
- 3. Adeltas: small slow (2-10m/s)
- 3 C fibers (unmyelinated) (.5-2.5m/s)
- 1. Cm: mechanosensitive
- 2. Ct: thermosensitive
- 3. Cp: polymodal
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It is the __________ strength of solutions and their ________ composition that elicits pain responses in human teeth.
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What are some of the changes induced by nerve fibers during pulpal inflammation?
- 1. Growth factors released causing nerve terminal sprouting
- 2. Reduce threshold of other nerves
- 3. Pulpal blood flow affected
- 4. Increase in size of receptive fields
- 5. Increased regional sensitivity
- 6.
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PDL contains these mechanreceptors.
Ruffini
from trigeminal ganglion or mesencephalic ganglion
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What are the two major mechanism of pulpal pain?
- 1. Dentinal sensitivity
- 2. Pulpal inflammation
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What are "silent" A fibers?
Slow conducting Adelta fibers NOT sensitive to hydrodynamic stimuli of the coronal dentin
activated by intense heat and cold that reaches pulp proper.
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Injury to the pulpodentin complex causes far reaching effects via the nerve fibers, describe
- 1. Signals go to ganglion and central pain pathways
- 2. Terminals release neuropeptides affecting vasodilation
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