pathophys of pain (wk9)

Question 1

pain definitions

Answer 1

Dysesthesia
Any abnormal sensation described by a patient as unpleasant

Paresthesia
A sensation that is typically described as “pins-and-needles” or “prickling”, but is not notably unpleasant

Analgesia
Reduction or loss of pain perception

Anaesthesia
Reduced perception of all touch & pain sensation

Hypoalgesia
Decreased sensation and raised threshold to painful stimuli

Hyperalgesia
Exaggerated pain response from a normally painful stimulus
Allodynia
Abnormal perception of pain from a normally non-painful mechanical or thermal stimulus

Hyperesthesia
Exaggerated perception of a touch stimulus

Causalgia
Burning pain in the distribution of a peripheral nerve

Question 2

how does pain differ from other perceptions like touch, taste, and smell

Answer 2

doest exhibit adaptation

Question 3

what type of pain is dermal pain

Answer 3

sharp or burning

Question 4

where are nociceptors distributed

Answer 4

many depths of skin and visceral organs

• Nociceptors are widely distributed through multiple depths in the skin
  ▪ “Dermal pain” tends to be described as sharp or burning
• Nociceptors are also widely distributed through many
  visceral organs
  ▪ Skeletal/cardiac muscle – dull, pressure-like pain
  ▪ Joints (synovium) and bones (periosteum) – many different characteristics (sharp, dull, aching)
  ▪ Blood vessels – usually dull
  ▪ Nerve roots and meninges
  ▪ Hollow viscera – often dull, cramping but can be sharp
  ▪ Mesothelial linings (peritoneum, pleura, pericardium) – often sharp
  ▪ Many organs can cause a dull pain due to stretching of the capsule

Question 5

4 types of nocicpetors

Answer 5

thermal
mechanincal
polymodal
silent nociceptors

Question 6

thermal nociceptors

Answer 6

activated by temperatures > 45 C or less than 5 C

Question 7

mechanical nocicpertors

Answer 7

activated by intense pressure applied to a structure (i.e. skin)

Question 8

polymodal nociceptors

Answer 8

activated by high intensity mechanical, chemical, or thermal stimuli

Question 9

silent nociceptors

Answer 9

receptors that are widely distributed through viscera (but can also be found in the skin) that do not normally transmit pain information
▪ Only “awakened” in a setting of continuous damage or inflammation

Question 10

c fibers

Answer 10

unmyelinated
slow velocity
slow pain and thermopreception and itching
dull, poorly localized

Question 11

A delta fibers

Answer 11

myelinated
fast
pricking pain and thermoception, localized

Question 12

C fibers vs A delta

Answer 12

C: unmyelinated, slow, poorly localized

AD: myelinated, fast, localized

Question 13

2 receptors type for nocicpetors?

Answer 13

transient receptor potential receptors (TRP) and acid sensing ion channels (ASIC)

Question 14

what other receptors for molecules do noccicpetors express in inflammatory process

Answer 14

prostaglandins, bradykinin, histmaine, substance P, serotonin, Ach, ATP

▪ Prostaglandins – most are G-protein-coupled receptors that block potassium channels (leading to depolarization)
▪ Bradykinin – activated by pro-inflammatory, pro- coagulant processes
* protein that circulates in the bloodstream (kininogen) is activated to form bradykinin in situations involving tissue damage

Question 15

example of activation of some receptors in found in nociceptive neurons can increase the activation of other receptors

Answer 15

bradykinin increases and sensitizes TRP receptors

Question 16

major nociceptive sensory pathway?

Answer 16

spinothalamic tract

Question 17

spinothalamic tractg

Answer 17

afferent
a delta and C fibers (cell bodies in dorsal root ganglion)

tract of lissauer= thinnest fibers (C fibers) bundle

contralateral; cross over

Question 18

4 other ascending pain pathways

Answer 18

1. spinothalamic tract
2. paleospinothalamic pathway
3. anterior spinothalamic tract
4. lateral spinothalamic tract

Question 19

spinothalamic tract cross over vibe

Answer 19

The fibres of the spinothalamic tract usually cross over (2nd order neurons) two or three levels superior to where the 1st-order neurons enter the spinal cord
▪ The fibres of 1st order neurons tend to ascend in a small fibre bundle (the tract of Lissauer) before crossing over and synapsing

Question 20

paleospinothalamic pathway

Answer 20

-more medial that spinothalamic tract
-ascneding
▪ Project through the medulla and synapse within a different set of
thalamic nuclei (the intralaminar nuclei)
▪ Also synapse in a wide variety of other brainstem areas:
* Midbrainreticularformation,peri-aqueductalgraymatter, hypothalamus
* Mayberesponsibleformuchoftheemotionaldistressandmood impacts of pain

Question 21

anterior spinothalamic tract for»

Answer 21

visceral pain

makes sense bc visceral organs are in front of spine

Question 22

lateral spinothalamic tract

Answer 22

localized skin associate pain

makes sense bc lots of skin ie love handles on lateral side of spinal cord

Question 23

fast pain vs slow pain

Answer 23

• Fast pain – well- localized, sharp pain carried by A-delta fibres
• Slow pain – poorer- localized, duller
  ▪ Carried by C- fibres
  ▪ Tends to last longer

Question 24

first pain vs second pain

Answer 24

first: high intensity and quick via A delta fibers (myelinated)

second pain is less intense and last way longer via c fibers (unmyelianted)

Question 25

top down modulation of pain- analgesia system

which brain area

which receptor and which fibers is it in more

Answer 25

periaqeudutal gray matter

opiate/ opiod MU receptors

release enkephalins, endorphins and dynorphins

c fibers have high [] of my opioid receptors bc

Question 26

gate theory of pain control

what is the nonnociceptive fiber

Answer 26

non nociceptive fiber at similar spinal level reduce pain by rubbing area bc activates inhibitory interneuron that inhibits the projection interneuron

Question 27

pain sensitivity and hyperalgesia from peripheral tissue damage and repetitive exposure to noxious stimuli

which chemicals?

Answer 27

bradykinin
histamine
prostaglandins
ATP, acetylcholine, serotonin

Question 28

peripheral vs central sensitization

Answer 28

peripheral: molecules released at the site of tissue damage or inflammation increase the effectiveness of nociception

central: synaptic remodelling in dorsal horns- increased effectiveness of pain transmission

Question 29

what fibers ar more Lilly to exhibit central sensitiization

Answer 29

C fibers

Question 30

pro inflammatory cytokines in central sensitization release what

Answer 30

nerve growth factor which increases BDNF from C fibers

molecules released at the site of tissue damage or inflammation increase the effectiveness of nociception

Question 31

antidromic vs orthodromic

Answer 31

▪ From periphery → spinal cord = orthodromic

▪ From spinal cord → periphery = antidromic

Question 32

what substances can C fibers release and what do they cause?

Answer 32

Substance P and CGRP

▪ Substance P can cause mast cell degranulation, vasodilation, and edema

▪ CGRP can cause vasodilation

Question 33

neurogenic inflammation

Answer 33

makes things hurt more

may seen maladaptive but if it hurts so much that you cant use it any more ift will protect against further tissue damage

recruit leukocytes for repair

and limit use to protect

Question 34

substance P

from which fibers

which receptor does it bind

Answer 34

C fibers

▪ Augmenting inflammation ▪ Learning & neurogenesis ▪ Mood disorders
▪ Nausea and vomiting
▪ Cell growth and angiogenesis

Nk-1 (neurokinin-1) receptor

Question 35

what makes c fibers transmit impulse for long periods of time (second pain0

Answer 35

substance P

• Substance P release→long-lasting depolarization of projection
  neurons via modulation of other cation channels

▪ A-delta fibres don’t release substance P – therefore their EPSPs from release of glutamate tend to last less time

Question 36

why does nerve injury sometimes cause pain instead of analgesia

Answer 36

pain gate theory

non nociciceptive (A-beta) vs nociceptive (c fibers)

• Injury to nerves tends to reduce the stimuli to the inhibitory interneurons→excessive activation of excitatory interneurons and nociceptive projection neurons

▪ A-beta fibres from “regular sensations” (vibration, touch) tend to stimulate inhibitory interneurons that reduce transmission of pain from projection interneurons
▪ C fibres that carry painful stimuli tend to inhibit the inhibitory interneurons
▪ Therefore, whether we feel pain or not depends on where the balance “sits” between nociceptive and non-nociceptive inputs

Question 37

pain and mood disorders

Answer 37

same brain area, inflammation, central sensitization

Question 38

referred pain

Answer 38

effect distant organs via dermatomes i.e. heart does T1-T4 in arms