Physiology

Front 1

1. How is pain defined?

What is nociception?

What are the two components of the sensation of pain?

Back 1

Pain is defined as an unpleasant sensation

Nociception is the process whereby pain is perceived by the CNS

1. The injurious (protopathic or tissue damage) component

**tissue damage component is dependent upon physical variables and can be quantated

2. Affective or psychologic component

Front 2

2. What does quantation include?

Back 2

1. Measurements of reflex activity

2. Neural pathways involved (including pain modulation systems)

3. Intensity of the stimulus

4. Degree of tissue damage

Front 3

3. What are pain receptors?

What do these "bare" endings contain?

Back 3

Pain receptors are unspecialized "bare" endings

Contain channels specific for protopathic stimuli such as:

1. Heat (TRPV1, 2, 3, & TREK-1)
2. Cold (TRPM8)
3. Chemicals (TRPV1, ASIC, DRASIC)
4. Pressure (MDEG, DRASIC, TREK-1)

Front 4

4. What does the affective (psychologic) component of pain depend upon?

Can the affective component be quantified?

What does the affective component lead to?

Back 4

Depends upon pre-history of pain and societal values

**highly variable among individuals

It is difficult to quantitate

Leads to fear, anxiety and avoidance behaviors

Front 5

5. How are pain thresholds across ethnic difference?

What does this suggestion?

How is pain perception among genders?

What is women's increased endurance to pain due to?

Back 5

Pain thresholds are similar across ethnic differences

Narrowness of variability in pain threshold suggest similar pain processing mechanisms

Slight gender difference - women are more sensitive to pain but can endure it longer

Due to more efficient pain modulation system
(most needed during gestation and parturition)

Front 6

6. Why does the perception of pain intensity vary widely among individuals?

(two sources of variability)

Back 6

1. Variability of the affective component

2. Alterations in the neural anatomy, above or below normal activity of the neural components and/or presence of certain pathologies

Front 7

7. When there is injury to pain transmission system what is the result of action?

b. What about when there is increased activity of modulatory system?

c. Abnormal neural activity?

d. Individual psychological differences?

Back 7

A. Lower pain intensity perception

B. Lower pain intensity perception

C. Increased pain intensity perception, even pain w/o noxious stimulus

D. Normal pain intensity perception, unpredictable response

Front 8

8. What does the quality of pain perception depend upon?

(two component)

Back 8

1. Sensory component

**dependent upon the intensity and/or duration of the stimulus

2. Affective component

Front 9

9. What characteristics do pain nerve display compared to general sensory nerve?

Back 9

1. High threshold

2. Don't plateau until they are damaged beyond repair

3. Once stimulated they keep increasing their AP frequency

4. Detection process ends when the nerve is destroyed by the stimulus

**pain will return as new pain nerves become connected again

Front 10

10. How is the relative AP frequencies for a pain nerve for heat compared to a general sensory nerve detecting warmth?

Back 10

General Sensory Nerve
-plateau
-take less energy (lower temperature) to adequately stimulate the warm receptor

Pain Nerve of Heat
-nearly straight line increase in AP frequency
-takes more energy (higher temp) to adequately stimulate the pain nerve

Front 11

11. What are the two types of nerve fibers that mediate nociception?

Back 11

1. A delta (myelinated)

2. C fibers (unmyelinated)

**have similar characteristics but have significant functional differences

Front 12

12. What type of pain do the A delta fibers mediate?

What stimulates A delta fibers?

What are A delta fibers termed and why?

Back 12

Mediate the fast, bright or sharp pain (OUCH!! pain)

**presence of myelin insured relatively rapid conduction velocity to CNS

Stimulated by protopathic mechanical and/or thermal stimuli
(heat, cold, or pressure)

Called high threshold thermo-mechano receptors (HTM's)

**B/c it takes a lot of energy to stimulate these fibers compare to general sensory fibers

Front 13

13. Where do A delta fibers enter the spinal cord?

Where do they synapse?

What do A delta fibers synapse onto?

Back 13

Enter the cord at tracts of Lissauer

Synapse in laminae I, II, & V of Rexed's laminae

Synapse onto nociceptive specific (NS) cells which are the 2⁰ nerves

Front 14

14. What do NS nerves respond to?

Why are these nerves call nociceptive specific?

What do the 2⁰ fibers do?

How is this route to the sensory cortex?

Back 14

NS nerves respond only to either heat, cold, or pressure

A NS nerve responsive to heat will not respond to cold or pressure

2⁰ fibers cross midline and ascend in neo-spinothalamic tract

Direct route to sensory cortex

Front 15

15. What do C fibers mediate?

What stimulates C fibers?

What are C fibers termed?

Back 15

Mediate slow, dull, burning, or achy type of pain
(OOHH!! type of pain - can rise to intolerable levels)

**slower conduction velocity to CNS due to absence of myelin

Stimulate by intense mechanical, thermal, and chemical stimuli

Polymodal nociceptors (PMN's)

Front 16

16. Where do C fibers enter the cord?

What do C fibers connect to?

What do the 2⁰ nerves do?

How is this route to the sensory cortex?

Back 16

Enter tracts of Lissauer (Rexed's laminae)

Connect to the wide dynamic range nerves (WDR's) of laminae I, IIa, & V

2⁰ nerves cross and form the paleospinothalamic tract

Less direct route to the sensory cortex

Front 17

17. What do WDR fibers respond to?

Back 17

Respond to heat, cold, pressure, and/or chemicals

Can also be stimulated by non-noxious stimuli such as pressure

**therefore, touch can also stimulate partially depolarized 2⁰ WDR pain afferents

Front 18

18. What do the interneurons to the reticular activating system (RAS) do?

What does the limbic cortex do?

Back 18

RAS increases alertness and deprives one of sleep

Limbic cortex inputs an emotional content to pain
(part of avoidance response)

Front 19

19. Where can pain thresholds be lowered (i.e. patient perceives pain more easily)?

What does this result from?

Back 19

In traumatized areas, partially traumatized areas, and even uninvolved areas

Results from mechanisms which mediate processes resulting in 1⁰ and 2⁰ hyperalgesia, allodynia and wind-up

Front 20

20. What does the volume of chemicals released by pain nerves as well as facilitation of the sensation of pain depend upon?

What in turn determines the intensity of the nociceptive stimulus?
(three variables)

Back 20

Intensity of the nociceptive stimulus

1. Extent of tissue damage

2. Involvement of inflammatory factors

3. Duration of pain
(involvement of neuropathic pain mechanisms)

Front 21

21. What happens when a needle sticks a portion of the skin?

What occurs as a result?

What is orthodromic conduction?

Back 21

Needle stick depolarizes nearby pain nerves

Orthodromic conduction occurs

Orthodromic conduction is nerve conduction along the normal route (into the CNS)

Front 22

22. As the pain nerves are branched what type of conduction takes place?

What does antidromic mean?

How can antidromic conduction take place?

Back 22

Antidromic conduction takes place

Antidromic is the direction of conduction not expected (away from the CNS)

It takes place b/c nothing can stop the eddy current and as a result orthodromic and antidromic conduction occur

Front 23

23. What will the antidromic eddy current do?

What will antidromic AP's do?

Where are these transmitters present?

What are the two transmitters released?

Back 23

It will depolarize the afferent nerve branches to threshold resulting in AP

Will depolarize the afferent endings of the pain nerves releasing transmitters

Transmitters are present in the afferent endings of pain fibers themselves

1. Substance P (SP)
2. Caclitonin gene related peptide (CGRP)

Front 24

24. Once released, what do the transmitters do?

Back 24

1. Diffuse to other nearby nerves

**transmitters are not rapidly activated

2. Transmitters depolarize the nearby nerves and AP result in nearby nerves

Front 25

25. What causes primary and secondary hyperalgesia?

Back 25

Back diffusion of transmitter to initial traumatized nerves

Foreword diffusion of transmitters to other uninvolved nerves

Front 26

26. What does short duration pain involve?

What causes primary hyperlagesia?

How does 1⁰ hyperlagesia affect pain perception?

Back 26

Antidromic conduction and release of SP and CGRP

Antidromic release of transmitters overly sensitizes the area of trauma

Increases pain perception of traumatized area

Front 27

27. What cause secondary hyperalgesia?

Where does the perception of pain in 2⁰ hyperalgesia come from?

Back 27

Antidromic release of transmitters depolarizes nerve in uninvolved areas to threshold

Perception of pain from undamaged tissue

Front 28

28. If injury involves cell damage then what do damaged/dying/dead cells release?

What is the concentration of this proportional to?

What do these released substances cause?

Back 28

Release inflammatory factors

[Inflammatory factors] is proportional to extent of damage

Released inflammatory factors result in vasodilation w/in effect area

Front 29

29. What are some result of vasodilation due to released inflammatory factors?

What are the three classic signs of inflammation?

Back 29

1. Swelling which deforms tissue and sensitizes other nerve causing dolar
(1⁰ and 2⁰ hyperalgesia enhanced)

2. Reddedning (ruber)
(increased blood flow)

3. Increased local temperature (calor) from increased blood flow

Calor, Ruber, & Dolar

Front 30

30. What type of receptors do 2⁰ nerves (NS and WDR nerves) have?

What stimulates AMPA and NMDA receptors on dorsal horn cells?

When do AMPA receptors depolarize the cell?

Back 30

AMPA and NMDA receptors

Stimulated by glutamate and SP released by 1⁰ pain nerves

AMPA receptors depolarize cell upon receipt of mild to moderate stimulation from the 1⁰ nociceptor nerves

**depolarization is via increase inward Na current

Front 31

31. When AMPA receptors receive mild to moderate stimulation what happens to the 2⁰ nerves?

What perception is there from AMDA receptors?

What does the slow re-uptake of transmitters allow the transmitters to do?

Back 31

[Na] inward current depolarizes the 2⁰ nerves

Perception is "mild to moderate" discomfort

Diffuse long distances resulting in development of wind-up, allodynia and possible trigger points

Front 32

32. What is windup?

What happens to the 2⁰ nerves during wind up development?

Back 32

An out of proportion response to pain

2⁰ nerves from the traumatized area are depolarized even further increasing AP frequency

Front 33

33. What does allodynia occur?

What happens to the 2⁰ nerves during allodynia development?

Back 33

Occurs when the 2⁰ pain fibers from un-traumatized areas are depolarized to threshold and consequent AP generation

2⁰ nerves from non traumatized areas are now firing giving the impression that these areas are also traumatized

Front 34

34. What happens during trigger point development?

Back 34

Pressures, etc. nerves also converge onto 2⁰ pain nerves especially the WDR's (convergence principle)

Pressure, etc. can thus stimulate AP's from the 2⁰ pain nerve that are depolarized to just below threshold

Front 35

35. What happens when the AMPA receptors are more strongly stimulated upon receipt of strong signals from the primary nociceptor nerves?

Back 35

1. Dorsal horn cells are depolarized even more

2. Greater depolarization causes the Mg block of the NMDA receptors to be released

3. Inward Ca current ensues

4. Significant increase in dorsal horn nerve firing due to inward gCa current increasing

Front 36

36. What important parallel event happens to the transmitters mediating this process?

Back 36

They are slowly inactivated by re-uptake and can thus diffuse for long distances

**other 2⁰ nerves from uninvolved areas are stimulated

**basis for the "alloydynia" phenomenon

Front 37

37. What does increased Ca influx into pain modulation nerves do?

What happens if the pain modulation nerves are not allowed to re-polarized and get rid of excess Ca?

What is a another mechanism for generation of "phantom limb" pain?

Back 37

It depolarizes them

They eventually malfunction and may die

**now no modulation of pain nerves

The lack of pain modulation will allow surviving nerves to still fire, giving the patient w/ an amputation the perception of pain from a limb that is missing

Front 38

38. What does very long continuos firing of 1⁰ pain fibers do?

What does the induction of oncogene c-fos & c-jun result in?
(five things)

Back 38

Alters 2⁰ nerves

1. Stimulation of second messenger cascades

2. Synthesis of protein FOS

3. Continual firing of 2⁰ nerve

3. Phantom limb phenomenon

4. Pain is difficult to impossible to manage

Front 39

39. What are reflex sympathetic distrophy (RSD) and casusalgia?

What casues RSK (CRPS 1)?

Back 39

Categories of pain mechanisms under the heading of complex regional pain syndrome (CRPS)

RSD results from trauma resulting in abnormal sympathetic nerve discharge

Front 40

40. What are the symptoms of RSD (CRPS 1)?

Back 40

1. No obvious damage to nerve

2. Sensory (hyperesthesia)
*increased sensitivity to sensory stimulation

3. Vasomotor
(temp or skin abnormalities)

4. Sudomotor
(edema or sweating abnormalities)

5. Motor
(decreased range of movement, weakness, tremor, or neglect)

Front 41

41. What are the symptoms of causalgia (CRPS II)?

Back 41

1. Apparent nerve damage

2. Similar appearance to RSD

Front 42

42. What is an example of a psychological component of pain modulation

What is this?

Beside the placebo effect what can stimulate pain modulation mechanisms?

Back 42

"Placebo Effect"

Believing that some element will bring relief from pain may indeed lower perception of pain

Touch or pressure

Front 43

43. How was the "gate theory" first observed?

What does the gate theory today pay more attention to?

Back 43

Pressure near the traumatized area relieves (somewhat) pain as if there are gates for pain and pressure which preferentially let pressure in

CNS integration

Front 44

44. What is the "gate theory"?

Back 44

Pressure stimuli near traumatized area are integrated in medulla

Efferents course via cortico-spinal tract to laminae I, II, & V where they inhibit laminae I, IIa, & V

Touch or pressure afferents "laterally inhibit" pain afferents

Front 45

45. What does recent research suggest reduces chronic pain?

What is the mechanism?

Back 45

Invasive and non-invasive stimulation of motor cortex

Mechanism:

1. Release of CNS endogenous opioids

2. Ortho and antidromic stimulation of intercortical neurons

Front 46

46. What can transcutaneous electroneural stimualtion (TENS) do?

What does TENS stimulate?

Back 46

Modulate pain

1. Stimulate muscle contraction

*pressure and touch due to muscle contraction stimulate pain modulation

2. Stimulate blood flow to affected area

*removes damaging chemicals
*improves tissue metabolism

Front 47

47. What can anticipation of pain do to the perception of pain?

What happens to the response to actual painful stimuli?

Back 47

Increase the perception of pain

**pre-sensitized to feeling something "painful"

**pressure/cold/warm can become misinterpreted as being "pain"

Response to actual pain becomes out of proportion and reinforces 1⁰ and 2⁰ hyperalgesia as well as wind-up and allodynia

Front 48

48. How can anticipation of relief from pain affect the perception of pain?

Back 48

May decrease the perception of pain

Relief of mental (and physical) stress may reduce patient anxiety

**Hypnosis and transcendental meditation may aid in patient management

Front 49

49. What is the mechanism of hypnosis associated with?

What are some drawbacks of hypnosis?

Back 49

Associated w/ a conscious mental effort to concentrate on something pleasant

1. Patients have to undergo training for this to become effective

2. Must be intelligent for training to be effective

3. Must want to be hypnotized

4. Come out of hypnotic state if perceive you are getting into unpleasant circumstances

*defense mechanisms sensing danger are not turned off

Front 50

50. What is an advantage of transcendental meditation (TM)?

What is a disadvantage?

Back 50

TM is very simple and easy to learn

Practitioners of TM can be rapidly brought out of their meditation by unexpected external stimuli