Pain And Therapeutic Targets Of Inflammatory Pain

Front 1

Is Pain simply a sensory function?

Back 1

Sensory and emotional. Is ALWAYS subjective

Hint 1

Each individual learns application of the word through experiences related to early life

Front 2

What are the 3 types of pain?

Back 2

1.Nociceptive pain:

2.Inflammatory pain

3.Neuropathic pain

Front 3

Describe Nociceptive pain

Back 3

Occurs when nociceptors are activate din response to noxious stimuli such as extreme temperature, acid or mechanical

Front 4

Describe Inflammatory pain

Back 4

Occurs when nociceptors are activcated and or modified by inflammatory mediators after tissue damage.

Front 5

Describe neuropathic pain

Back 5

Occurs when damage occurs to the central or peripheral nervous system. Pain is sensed with no identifiable protective or healing role.

Hint 5

Most challenging to treat

Front 6

In what 3 ways can pain affect the Canadian economy?

Back 6

1.Costs to the individual

2.Costs to society

3.osts to healthcare

Hint 6

1.loss of earnings, daily activities, losss of socialization, leisure time

2.Loss of production

3.Inpatient and outpatient attendances,

Front 7

List some factors that can lead to addiction?

Back 7

Poverty, trauma/abuse, genetics, lack of education, experimentation, social groups

Front 8

Although women have lower pain thresholds suggested by studies, little evidence exists to sugest that men and women differ significantly in their sensitivity to clinical pain. Differences are most likely due to the stages of brain processing associated with>?

Back 8

Emotion

Front 9

Clinical pain experience can vary across racial and ethnic groups with the greatest difference seen in what measures of pain>?

Back 9

Emotional

Front 10

What pain assessment developed in 1971, classified pain into 3 dimensions including sensory, affective/motivational, and Cognitive/evaluative?

Back 10

McGill Pain Questionnaire

Hint 10

Categorized words into 5 groups

Front 11

Which nociceptors are myelinated , thermal, and mechanothermal, are distributed all over the body surface within the muscles and joints, and cause sharp fast pain?

Back 11

Alpha Delta fibres

Hint 11

Responsible for the first pain: initial sharp pain

Front 12

What fibres are non-myelinated , polmonal heat, chemical and cause a slow burning pain?

Back 12

C fibres

Hint 12

Responisble for second pain: Dull, poorl localized and aching pain that lasts beyond termination of the pain stimulus.

Front 13

What type of nociception, occurs with distension and ischemia and is less localized than peripheral nociception due to a relaively low receptor density?

Back 13

Visceral nociception

Front 14

Visceral nociception is innervated by 2 types of afferent fibres. High and low threshold fibres. What is the role of each?

Back 14

High: Respond to mechanical pain

Low: Encode magnitude of pain

Front 15

What is a silent nociceptor?

Back 15

Nociceptors can be sensitized if inflammation occurs

Front 16

What is referred pain?

Back 16

Describes pain felt at a site remote from the site of the original stimulus.

Front 17

Most Primary afferent nociceptors enter the spinal cord via the what?

Back 17

Ventrolateral part of the dorsal horn

Hint 17

They then proceed to synapse with 2nd order neurons in the dorsal horn nerve fibers in the dorsal horn

Front 18

The trigemial pain and temperature system carries information about pain senses from the face/. After synapse in the medulla what tract carries them to thalamus and sematiosensory regions of the brain?

Back 18

Trigeminothalamic tract

Front 19

Pain to other regions of the body other than the face are carried to higher brain centers via what tact?

Back 19

spinothalamic tract

Front 20

Under what condition in the Gate control theory does nociception occur>?

Back 20

When there are more C or Alpha delta fiber stimulation than Alpha Beta fibers

Front 21

In the Gate control theory , under what two conditions is the gate closed?

Back 21

More Alpha beta fibers than C or Alpha Delta fibers. 2. When no input comes in then the inhibitory neuron prevents the projection neuron from sending signals to the brain

Front 22

What is the term for increased pain sensitivity? (Can occur following inflammation)

Back 22

Hyperalgesia

Hint 22

Responsible for allodynia

Front 23

What is allodynia?

Back 23

Pain from a stimuli that does not normally envoke pain

Hint 23

Formerly silent nociceptors become response following sensitization)

Front 24

Inflammatory mediatiors can directly excite nociceptors or sensitize them. What are some examples of these mediators?

Back 24

cytokines, growth factors, amines and prostanoids

Front 25

What are two different mechanisms to induce peripheral sensitization?

Back 25

1.Phosphorylation of ion channels already present in the plasma membrane such as PKA, PKC, or Src

2. Alteration of cell surface expression of ion channels through differential trafficking

Hint 25

Note* PKA activation requires GPCR signalling pathway same as other mothers that phosphorylatre ion channels. ALl ghave unique signally cascades

Front 26

Which ion channel has a thermally sensitive channel expressed in somatosensory neurons and is activated by Physical, chemical stimuli such as heat , low ph ethanol?

Back 26

TRPV1

Hint 26

part of the transient receptor potential family (TRP)

Phosphorylation of this ion channel by PKA, PKC ir SRC leads to sensitization of avariety of stimuli, can also get increased trafficking of receptors to the cell surface

Front 27

Inflammation increases the expression of sodium channel subtypes in what fibres?

Back 27

C fibres

Front 28

What subunits of sodium receptors have phosphorylation motifs for PKA and PKC?

Back 28

Alpha subuints

Front 29

Phosphorylation of sodium channels by PKA has what effect on excitation?

Back 29

Increaseed!

Front 30

Phosphorylation of Potassium channels by PKA does what ot potassium channel conductance?

Back 30

decreases conductance

Front 31

A decrease in potassiuum channle conductance does what to neuronal excitability?

Back 31

Increases excitability

Hint 31

Potassium channles normally serve to dampen excitation potentials

Front 32

Sodium channels are made of what two subunits? Which subunit modulates kinetic and voltage sensitivyty of the pore?

Back 32

Beta subunit, alpha,

Beta

Front 33

Mutation to what class of sodium channels cause epilepsy?

Back 33

Nav 1.1, 1.2, 1.3

Front 34

Mutations to what class of sodium receptor can cause pain disorders?

Back 34

NA 1.7

Front 35

What gene encodes the NA 1.7 sodium channel?

Back 35

SCN9A

Front 36

Mice that have a knockout of NA 1.7 in the dorsal root ganglion have no change in their thresholds of heat induced pain but ....?

Back 36

Do not develop pain or hypersensitivity in response to inflammatory stimuli.

Hint 36

Suggests an important role in detecting pain in response to inflammationm

Front 37

What autosomal dominant disorder is characterized by attacks of symmetrical burning pain of feet, lower legs and hands?

Back 37

Primary Erythermalgia

Hint 37

Na 1.7 disorder

Front 38

Why is hyperexcitability of the DRG abd hyperalgesia seen in Primary Erythermalgia?

Back 38

Mutations in linker region cause channel to be acttivated by smaller than normal depolarizations, and a slower DEACTIVATIOn step

Front 39

What autosomal dominant pain disorder is characterized by sudden attacks of flushing and pain at different sites with increased intensity upon reoccurence? (typical affected areas are the buttocks, rectum and ocular layers)

Back 39

Paroxysmal extreme pain disorder

Hint 39

NA1.7 disorder

(Attacks may be provoked by yawnign crying or spontaneously)

Front 40

Is Na 1.7 channel function increase dor decreased a s a result of Paroxysmal extreme pain disorder? Primary Erythermalgia?

Back 40

Increased, increased

Front 41

What autosomal recessive pain disorder, results form nonsense mutations, leaving individuals with an inability to fell pain?

Back 41

CIP ( Channelopathy-associated insensitivity to pain)

Hint 41

NA 1.7

Front 42

Is channel function increase dor decreased in CIP?

Back 42

ABSENT

Front 43

Inflammatory pain begins with tissue damage, followed by activation of inflammatory cells, followed by the release of inflammatory mediators, then sensitization of DRG neurons. What inflammatory mediators are we focusing on in the coursE?

Back 43

Prostaglandins and Bradykinins

Front 44

Endothelial damage, activation of hageman factor, prekallikrein, kallikrein, which then ?

Back 44

cleaves kininogen to bradykinin

Front 45

What is suggested by the fact that injection of bradykinin into the skin produces dose-dependent pain and heat hyperalgesia?

Back 45

Bradykinin is capable of excting and sensitizing nociceptors to heat

Front 46

What two bradykinin receptors are involved in pain and inflammation? What is the role of each?

Back 46

B1 are involved in the chronic phase. B2 involved in acute phase of pain

Front 47

Describe the regulation of B1 and B2 bradykinin receptors?

Back 47

B1: limited desensitization

B2: Regulated by short term mechanisms, such as desensitization and down regulation

Front 48

what 3 things are caused by the binding of Bradykinin to B2 receptors on neurons?

Back 48

1. Induced release of neurotransmitters from neurons, such as substance P

2.Decrease threshold of ion channel

3. Decrease activity of k channels

Front 49

How do prostaglandins mediate Redness and edema?

Back 49

Increasing arterial dilation and increasing microvascular permeability

Front 50

Where can pain result from the actions of prostaglandins??

Back 50

Peripheral sensory nerves, the spinal cord or brain

Front 51

In the spinal cord , what two enzymes are constitutively produced to allow for the production if prostaglandins from arachidonic acids??

Back 51

COX-1, and COX-2

Front 52

There are 4 types of prostaglandin E2 receptor, all are GPCRs, which two are covered in this course?

Back 52

E1, E4

Front 53

DAG- PKC - Phosphorylate TRP channel - sensitization - hyperalgesia. Describes what prostaglandin receptor?

Back 53

E4

Front 54

ATP-cAMP= PKA- Phosphorylates TRP, calcium, sodium channels, - hyperalgesia. Describes cascade of what prostaglandin receptor?

Back 54

E1

Front 55

One way to stop pain is by using what against prostaglandins?

Back 55

NSAIDS )aspirin)

Hint 55

Note prostaglandins have many functions in the body, do not want all inhibited!