N-37 Pain I

Front 1

What is pain?

Back 1

Unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage

Front 2

Pain is always what?

Back 2

Subjective (since it is unpleasant [if not, it’s not pain] and emotional [if it’s bothering you, there’s an emotional component to it])

Front 3

What are the 3 components of pain?

Back 3

1) Sensory (discriminative) [i.e. location, character, duration, intensity], 2) affective (motivational), and 3) cognitive (evaluative) [what are you going to do about it and how does your environment affect your perception]

Front 4

how can one stimulus affect two different people?

Back 4

may be incredibly painful to one person and hardly affect another - it is SUBJECTIVE and uniquely individual. so you cannot tell your patients how much pain they are in

Front 5

what are some factors that pain depends on?

Back 5

biological, psychological, and social factors. varies across and within populations

Front 6

treatment of pain is often ____. why?

Back 6

treatment is often inadequate because of 1) uncertain diagnoses, 2) social stigma, 3) lack of effective treatment and 4) lack of patient and clinical knowledge about how to best manage pain

Front 7

you perceive pain and the neurobiological equivalent i.e. how the nervous system responds is ____

Back 7

Nociception (e.g. you perceive pain from a cut, burn, tissue damage etc. and nervous system response is nociception)

Front 8

you perceive hyperalgesia and the neurobiological equivalent is ____.

Back 8

hypersensitivity in the nervous system

Front 9

what is hyperalgesia? example?

Back 9

heightened sensitivity to an already painful stimulus (e.g. a really hot shower is painful but a really hot shower when badly sunburned -> agony)

Front 10

you perceive primary hyperalgesia i.e. at the site of the injury and the neurobiological equivalent is ____

Back 10

peripheral sensitization (e.g. the reddened area around a paper cut)

Front 11

you perceive secondary hyperalgesia i.e. away from the site of the injury and the neurobiological equivalent is ____

Back 11

central sensitization

Front 12

what happens with central sensitization?

Back 12

an increase in excitability in dorsal horn neurons and further up in pain pathways in the brain

Front 13

you perceive allodynia and the neurobiological equivalent is ____

Back 13

allodynia does not imply a mechanism* (several hypotheses) term used to describe a clinical condition

Front 14

what is an example of allodynia? when do you see it?

Back 14

perception of pain to a normally non-noxious/non-painful stimulus e.g. lightly rubbing of the skin or blowing cool air may be perceived as intense, burning pain. often seen in nerve injuries

Front 15

what is more common, hyperalgesia or allodynia?

Back 15

hyperalgesia

Front 16

explain

Back 16

when you have an injury, you see a leftward shift in the stimulus-pain response function. so now a mild slap on the back e.g. on sunburned skin becomes much more painful. allodynia is where light touch produces a painful stimulus

Front 17

what is the role of pain normally?

Back 17

you can’t survive without “normal” or “nociceptive” pain -> it is animportant signal that something is wrong e.g. you need to protect injured area and let it heal. the curve should shift back to the right

Front 18

what is pathophysiological pain? when does it occur?

Back 18

in some cases, especially with nerve damage injury either in periphery or CNS, the curve may remain shifted to the left -> pathophysiological pain -> chronic pain -> pain becomes the disease e.g. more than three months

Front 19

what happens in many chronic pain cases?

Back 19

the pain has become the disease. the cause of the pain has gone away, and is no longer apparent, but there have been changes in the nervous system involving plasticity in the brain and nervous system. the curve stays shifted

Front 20

in chronic pain, what other types of changes do you often see?

Back 20

in psychological state and mood

Front 21

as far as mood, pain and ____ go together. how do they interact?

Back 21

depression and pain go together; which came first? they modulate one another

Front 22

whether pain is good or bad depends on the ____

Back 22

circumstances

Front 23

Acute pain is ____ vs. chronic is _____

Back 23

protective; it is a symptom of something else. Chronic pain is useless. it serves no useful purpose and can be thought of as a disease state itself*

Front 24

as far as time scale, pain can be ____ or ____

Back 24

acute / transient or chronic

Front 25

some examples of transient pain are:

Back 25

touching a hot coffee pot, pinprick (e.g. may cause withdraw reflex but does not last long)

Front 26

what is the course of acute inflammatory pain typically like? what are some examples?

Back 26

(chemical, sprains, breaks, minor burns, postoperative etc…) hurts for a couple of days, weeks, perhaps months but you will experience less pain as the injury heals

Front 27

what are three categories of pathophysiological pain? describe its course

Back 27

1) chronic inflammatory pain (e.g. arthritis), 2) neuropathic pain (diabetic, chemotherapy-induced) or 3) central pain (post-stroke pain) -> damage to the nervous system that does not go away; take a very long time, may last for years

Front 28

5 types of pain include:

Back 28

Somatic vs. visceral; Primary hyperalgesia vs. secondary hyperalgesia; Referred pain

Front 29

Chronic pain can manifest in many forms (3 examples)

Back 29

reflex sympathetic dystrophy, herpes zoster / post-herpetic neuralgia, ulcerative colitis

Front 30

Pain is a ____ experience including ____, ____ and ____ components.

Back 30

Pain is a multidimensional experience including sensory, emotional and cognitive components.

Front 31

Hyperalgesia is ____ pain

Back 31

hyperalgesia is increased pain

Front 32

allodynia is ____ pain

Back 32

new pain

Front 33

cutaneous / somatic pain refers to pain from

Back 33

skin, muscle, bone or joint

Front 34

visceral pain refers to pain from

Back 34

all of your internal organs e.g. reproductive, the GI tract, cardiovascular organs

Front 35

size and speed of A-beta fibers?

Back 35

larger, myelinated so fast conductance

Front 36

size and speed of A-delta fibers?

Back 36

smaller, myelinated, also fast

Front 37

___ fibers are unmyelinated

Back 37

C fibers are unmyelinated

Front 38

where in your viscera can you feel low-threshold stimuli?

Back 38

mostly you can’t but you can feel some in your esophagus, stomach, rectum

Front 39

what does specificity encoding refer to?

Back 39

one group that encodes innocuous stimuli (Aβ, Aδ), response increases as intensity increases until you reach the pain threshold. as you move into the noxious range, the second group of fibers fire

Front 40

what does intensity encoding refer to?

Back 40

when one afferent will encode the entire range from innocuous to noxious (e.g. some viscera fibers)

Front 41

when do you feel noxious stimuli from the liver?

Back 41

only when there is significant disease / pathology e.g. tumor

Front 42

compare and contrast cutaneous with visceral pain

Back 42

Front 43

in the spinal cord, how are the cutaneous nociceptive afferents spread?

Back 43

not spread out very far, they have relatively small terminal arborizations in the dorsal horn

Front 44

describe the somatotopic organization of cutaneous nociceptive afferents in the SC in general

Back 44

the lower extremities are more medial vs. the arms are more lateral (come in later)

Front 45

where in the spinal cord is innervation from the toes?

Back 45

come in through the DRG and terminate in the medial part of the dorsal horn at the lumbar enlargement.

Front 46

as you move up and around the foot, what’s the somatotopic organization in the SC?

Back 46

you move up and lateral around the horn and makes its way up to form the homunculus

Front 47

what is the functional importance of the somatotopic localization of cutaneous afferents in the spinal cord?

Back 47

this allows you to localize where the noxious stimulus occurs, what part of your body is hurt (e.g. step on a tack and hurt your heel vs. your toes); discrete map of projections

Front 48

in the spinal cord, how are the visceral nociceptive afferents spread?

Back 48

the axon comes in and sends off branches that project into the superficial and deeper dorsal horn as well as contralateral side; the rostral/caudal projection of the afferent is spread over 5-10 SC segments, “all over the place”; huge terminal arborization

Front 49

what is the functional consequence of the dispersed visceral afferent projection in the SC?

Back 49

you lose your somatotopic organization, you don’t know where the pain is exactly

Front 50

how will your patients will feel belly pain?

Back 50

more generalized abdominal / visceral pain; it’s poorly localized so you don’t know *where* the noxious stimulus causing your pain; you can’t localize it (e.g. ulcer could be anterior/posterior, gastric/duodenal etc.)

Front 51

how many synapses do visceral afferent fibers synapse on?

Back 51

hundreds if not thousands of neurons, and then you lose the ability to localize where the stimulus is coming from

Front 52

how much of the DRG is visceral afferent vs. somatic afferents

Back 52

visceral afferents make up AT MOST ~10% of DRG (fewer cells innervate the viscera) vs. 90% afferents make up somatic cells

Front 53

how does innervation density vary with different parts of your body?

Back 53

certain parts of your body allow you to discriminate better (e.g. fingertips and lips) vs. trunk of your body (with the 2-point measure); impact your perception of stimuli including noxious stimuli

Front 54

why is visceral pain challenging?

Back 54

you can’t really tell where visceral pain is coming from; can be difficult for patients -> worrisome and challenging for clinicians to know how to treat it

Front 55

compare and contrast muscle afferents with visceral and cutaneous afferents

Back 55

muscle afferents fall in-between; you may know the muscle (e.g. hamstring) so some localization but you don’t really know where in the hamstring the damage has occurred; their terminal arborizations are much larger than the cutaneous afferents but much smaller than visceral afferents; affects your perception

Front 56

what is step 1 in a noxious stimulus evoking pain?

Back 56

Step 1: Primary Afferent Nociceptor Signaling: Activation and Sensitization

Front 57

what is activation?

Back 57

activation is a stimulus that causes the primary activation to fire. i.e. you stimulate and you get a response

Front 58

explain

Back 58

applying substance P here gives you a lower response but the cells are still responding and applying the stimulus N still results in the firing i.e. activation

Front 59

what is sensitization

Back 59

sensitization is doing something that will increase the ability of the primary afferent to fire i.e. will lower the threshold or raise the response to a given stimulus intensity

Front 60

explain

Back 60

apply stimulus B and you get a response but after giving PGE2 (prostaglandin E2), you get a much greater response which eventually returns to normal / baseline

Front 61

how are nociceptor activation and sensitization related?

Back 61

Nociceptor activation does not always lead to sensitization and sensitization can occur without nociceptor activation

Front 62

give an example of sensitization

Back 62

when you get sunburned, the pain may go away after a bit but your skin may remain sensitized so if you get a slap on the back or take a hot shower, it hurts more; it gives you a much greater response

Front 63

for the most part, how does activation work?

Back 63

through ionotropic receptors i.e. receptors and channels that open and allow chemicals to run through them

Front 64

what are the 4 categories of channels involved in activation?

Back 64

mechanical, thermal, or chemical transducers and ligand-gated channels

Front 65

what is Nav1.8?

Back 65

a sodium channel found in nociceptive afferents

Front 66

what is TRP-V1?

Back 66

a receptor that responds to capsaicin, as well as heat and changes in pH; main receptor for spicy foods

Front 67

what is TRP-M8?

Back 67

receptor involved in cool sensation

Front 68

what is TRP-A1?

Back 68

also a receptor involved in cool sensation

Front 69

what is P2X3?

Back 69

a purinergic receptor

Front 70

what is DRASIC?

Back 70

an acid receptor, sense changes in pH

Front 71

what are 7 stimuli involved in activation of nociceptive primary afferent terminals?

Back 71

5-HT, ATP, Glu, ACh, H+, Capsaicin, Noxious heat

Front 72

how do activators affect channels?

Back 72

when they bind to the receptors they cause the channels to open up and allow influx of Na+ or Ca++ into the cell, which causes it to start to fire

Front 73

what type of receptors does sensitization work through?

Back 73

through G-protein coupled receptors i.e. 7 transmembrane proteins that bind to different chemicals and activate through GDP-alpha/beta subunit complexes -> GTP -> second messenger pathways (activating kinases)

Front 74

when second messenger pathways are activated during sensitization what 3 things can happen downstream?

Back 74

kinases can cause phosphorylation of ion channels that either 1) open ion channels (excitatory) or 2) close ion channels (inhibitory) or 3) activated voltage-gated, Ca++ activated channels to increase their activity

Front 75

what are the effects of sensitization on depolarization?

Back 75

through sensitization you can increase the amount of depolarization (initially caused by activation) or lower the threshold to achieve the same level of depolarization -> action potentials -> information goes to the spinal cord

Front 76

what’s an example of inhibitory G proteins involved in nociception?

Back 76

opioids, that work in the periphery, help reduce activation of Ca++ channels and work to activates K+ channels, which tend to hyperpolarize cells -> puts the brakes on the excitation

Front 77

what are some members of the other large class of receptors?

Back 77

activated by Growth factors (NGF), Hormones (e.g., cortisol, estrogens), Cytokines (IL-1β, TNFα, IL-6) i.e. chemicals released from site of injury or in response to infection

Front 78

how does this third class (GF, hormones, cytokines) work?

Back 78

slower (hours to days) but can lead to changes in transcription of receptors, ion channels and transmitters; can change responsiveness of primary afferent terminals; *can* act on longer-lasting scale to modulate how the primary afferent responds to different types of stimuli

Front 79

noxious stimuli produce an ____ of chemicals that will activate and work at ____ different types of receptors

Back 79

noxious stimuli produce an array of chemicals that will activate and work at all of these different types of receptors

Front 80

Afferents use different ____ strategies depending on the ____ ____.

Back 80

Afferents use different encoding strategies depending on the target tissue.

Front 81

what is the consequence of more discrete central projections (terminal field in the spinal cord)?

Back 81

contributes to stimulus localization.

Front 82

what happens with divergent central projections?

Back 82

leads to loss of somatotopic organization.

Front 83

compare and contrast somatoptopic organization and localization of cutaneous, visceral and muscle input?

Back 83

Cutaneous input is somatotopically organized, visceral input is not and is poorly localized. Muscle input is somewhere in between.

Front 84

Afferents can be activated by what?

Back 84

stimuli that bind or activate ligand-gated ion channels.

Front 85

Afferents can be sensitized by what?

Back 85

substances that bind metabotropic receptors (G-protein coupled receptors).