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Physiology > Peripheral Mechanisms of Pain > Flashcards

Peripheral Mechanisms of Pain Flashcards

1
Q

Describe the characteristics and stimuli of Type A-Delta fibers….

A

Small, lightly myelinated fibers.

  • 1st pain (sharp)
  • Fast conduction
  • Well localized
  • Mostly mechanical stimuli
  • around 13% of cutaneous nociceptors
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2
Q

Describe the characteristics and stimuli of C-fibers..

A

Tiny Unmylinated fibers

  • 2nd pain (dull/burning)
  • Poorly localized
  • Chemical, mechanical , thermal & polymodal stimuli.
  • Around 87% of cutaneous nociceptors
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3
Q

_______ MAY play a role in mechanical nociception.

A

ENaCS (epithelium sodium channels)

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4
Q

What are TRP’s and what is their role?

A

Transient receptor potentials are a large family of receptors transducing chemical and thermal nociception.

  • also involved in Non-noxious thermal transduction
  • also found in odontoblasts (possible role in tooth pain)
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5
Q

TRP receptors found on the trigeminal sensory fibers respond to what?

A

Chemicals to mediate chemesthesis.

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6
Q

What is Chemesthesis?

A

Response of c-fibers (A-delta)
- sensations include: burning, tingling (carbonation) astringency, pungency. (capsaicin spicy food, Salt water in wound)

*do not confuse with SPECIAL CHEMICAL senses such as taste and olfaction, these are not the same.

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7
Q

What does a Vanilloid Receptor do?

A 
AKA: TRPV1 or V1 receptor
Responds to:
- Capsaicin 
- Heat 42 degrees
- protons 
* stimulation of Vanilloid receptor results in influx of cations (Na+ and Ca++)
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8
Q

Which branches of the trigeminal nerve have prominent chemesthesis functions?

A 
Nasal = ethmoid branch (sensitive to smelling salts such as ammonia) Ch
Oral = posterior palatine, Nasopalatine and lingual nerve
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9
Q

Chemesthesis is mediated by _______.

A

TRP receptors

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10
Q

T or F, Chemesthesis is responsible for mostly aversive sensations.

A

True, probably won’t notice “banana” or “Salty”

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11
Q

What are the “Removal” reflexes associated with chemesthesis?

A
  • salivation
  • coughing
  • tearing up
  • sneezing
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12
Q

What dental compounds can activate Chemesthesis?

A

zinc phosphate, organic solvents, acrylic monomers & disinfectants

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13
Q

T or F, Capsaicin drugs can be used for the treatment of certain pain.

A

True, can be used to treat postherpetic neuralgia

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14
Q

Explain what happens after intense or repeated stimulation of primary afferent nociceptors?

A

Desensitization (pain relief cream like icy hot does this)

* capsaicin can desensitize primary afferent nociceptors

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15
Q

What innervates the tooth dentin tubules and pulp?

A

Dentin tubules = A-delta fibers (Mechanical and thermal sensitivity) Sharp pain

Pulp chamber = C-fibers (thermal sensitivity and chemosenstivity to inflammatory mediators) dull throbbing pain

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16
Q

Dentinal ______ fibers respond to mechanical forces.

A

A-delta fibers

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17
Q

Dental ____ fibers respond to Temperature.

A

A-fibers *The sensation from this is sharp pain

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18
Q

With A-delta fibers, Increased nerve activity is associated with what?

A

Increased pain

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19
Q

_______ fibers respond to algesic stimuli such as Bradykinin.

A

Pupal C-fibers

*Bradykinin causes Dull burning sensation

20
Q

How do we get sharp pain from mechanical, thermal and even chemical stimuli when applied to dentinal tubules?

A

Theories of Sharp pain

  1. Neuron Theory = cannot be ruled out for thermal pain.
  2. Hydrodynamic Theory = hydrostatic pressure directly applied to exposed dentin tubules.
  3. Odontoblast theory
21
Q

How does the presence or absence of a smear layer affect the hydrostatic activation of pain?

A

If the Smear layer is dissolved, it takes much less hydrostatic pressure to cause pain. *EDTA is used to dissolve smear layer.

22
Q

What are the Hypothetical steps in Odontoblast signaling?

A
  1. Depolarization by various TRP Receptors
  2. Initiation of action potential
  3. Release of ATP via membrane channels
  4. Afferent nerve response via P2X3 receptors.
23
Q

What are the Odontoblast Mechanoreceptors?

A

TRPV4
TRPM3
TRPP1
TRPP2

24
Q

What are the Hydrodynamic Mechanoreceptor?

A

TRPV1 (Osmoreceptor)
TRPV2
TRPA1 (Confusion between Cold and air puff)

25
Q

What is Hyperalgesia?

A

Greater responsiveness to stimuli (non-painful stimuli causes pain)

  • pain is spontaneous
  • pain is prolonged
26
Q

What are the peripheral mechanisms that cause Hyperalgesia?

A
  1. Thermal or Mechanical injury
  2. Damage that causes bleeding =
  3. Damage leading to infection & Immune response
27
Q

Describe the mechanism of Hyperalgesia via Thermal or mechanical injury….

A
  1. Thermal or Mechanical injury = C-fiber responds and releases neuropeptides substance P (SP) or CGRP
    * SP stimulates mast cells, mast cells release Histamine, stimulate histamine.
    * CGRP = vasodilation and swelling = mechanical stimulus to c-fiber.
28
Q

Describe the mechanism of Hyperalgesia via Damage that causes bleeding….

A
  1. Damage that causes bleeding = Same factors as thermal and mechanical stimulation AND CLOT FORMATION -> bradykinin -> stimulates C-fibers
    * Platelet products from blood (5-HT) serotonin - stimulates C-fibers.
29
Q

Describe the mechanism of Hyperalgesia via Damage leading to infection & immune response…

A

Damage leading to infection and immune response:

  • Prostaglandins sensitize c-fiber rather than cause direct excitation.
  • Cytokines can also sensitize C-fibers
  • Protons released in inflamed tissue stimulate vanilloid receptor and produce sensitization.
30
Q

What is the Role of NGF in Peripheral Sensitization?

A

NGF (Nerve growth factor) induces local receptor trafficking retrograde transport to promote gene expression.

31
Q

True or False, Prostaglandins directly depolarize neurons.

A

False they do not, they block SK channels that results in making cell more excitable.

32
Q

How does sensitization of Vanilloid receptor (TRPV1 or V1) occur?

A
  • Inflammation leads to lower threshold by the following events:
    1. Presence of inflammatory mediators (Bradykinin & protons)
    2. Ca ++ activated phosphorylation or VR1 receptor (TRPV1)
    3. Increase in receptor number
  • Receptor now activated at 22 degrees instead of 42!!!
33
Q

What are examples of Inflammatory mediators that are released in response to Neurogenic inflammation?

A
  • Substance P (From the nociceptor itself) stimulates histamine release.
  • CGRP produces swelling (Mechanical stimulus)
34
Q

What 3 things are involved in Direct stimulation of Nociceptors?

A
  • Histamine (Mast cells)
  • Bradykinin (blood clotting)
  • 5-HT (Blood platelets)
35
Q

What 3 things are involved in Sensitization of nociceptors?

A
  • Prostaglandins (Effect on K+ (SK) Channels)
  • proton release in inflamed tissue (TRPV1)
  • NGF (Nerve growth factor) increases receptor trafficking
36
Q

What is allodynia?

A

A type of Hyperalgesia, response to non-painful stimuli is pain.

37
Q

Sensitization of TRP1 (Vanilloid Receptor) = ?

A

Lowered temperature threshold. Possible allodynia.

38
Q

Sensitization by prostaglandins = ?

A

Lowered mechanical threshold. Possible allodynia.

39
Q

Why can response to painful stimuli be even greater than normal with Hyperalgesia?

A

Action of inflammatory mediators augments (adds to) peripheral stimulus.

40
Q

What are the 4 Pain Pathologies associated with Nerve Damage?

A
  1. Causalgia = burning pain
  2. Allodynia = light touch leading to pain
  3. Sympathetic nerve dystrophy = temperature induced pain.
  4. Phantom sensations = sensation in denervated tissue.
41
Q

What are Neuromas?

A

Nerve sprouting collar sprouting that can sometimes cause painful sensations.

42
Q

Describe the Process of Schwann cell regeneration…

A
  1. Schwann cells proliferate
  2. Produce laminin for substrate for regenerating axons
  3. Schwann cells secrete NGF (Nerve growth factor)
  4. NGF transported to ganglion cell body
  5. NGF regulates gene expression and promotes “Sprouting”.
43
Q

Normal up regulation of receptors and channels = ?

A

TTX resistant Na+ channels?

44
Q

Abnormal up regulation of receptors and channels = ?

A

Sympathetic fibers sprout and release noradrenaline and more sodium channels (both TTX sensitive and resistant) develop.

45
Q

______ is a mechanism for allodynia and referred pain.

A

Ephaptic transmission

46
Q

What is ectopic Discharge? What causes it?

A

Abnormal spontaneous nerve response.

  • Prolonged responses to known stimulus
  • Initiation of response from atypical site (such as ganglion)
  • Response to Catecholamines
  • Results from injury-induced increase in Na+ channels!
  • Activity is evoked locally: not by “normal” receptor ending
47
Q

What is Ephaptic Transmission?

A

the passage of a neural impulse from one nerve fiber, axon, or dendrite to another through the membranes. The mechanism may be a factor in epileptic seizures.

Physiology (9 decks)

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