Anatomy and Physiology of Pain

Question 1

What is pain? What type of information is it usually associated with?

Answer 1

An unpleasant sensory and emotional experience associated with actual or potential tissue damage. A cerebral construct - a perception usually associated with tissue-damaging stimuli.
Nociceptive information

Question 2

What are the physiological mechanisms of pain?

Answer 2

Transduction
Transmission
Perception
Modulation

Question 3

What is transduction?

Answer 3

Noxious stimuli translated into electrical activity at sensory nerve endings.

Question 4

What is transmission?

Answer 4

Propagation of impulses along pain pathways

Question 5

What is perception?

Answer 5

Discrimination/affect

Question 6

What is modulation?

Answer 6

Positive and negative modulation occurs. Transduction, transmission and perception are modified.

Question 7

What is another name for acute pain?

Answer 7

Normal or nociceptive

Question 8

What is a nociceptor?

Answer 8

A sensory neuron transducing potentially harmful stimuli. Normal pain results from activity of these.

Question 9

What are the two main nociceptors involved?

Answer 9

C fibres

A delta fibres

Question 10

What do the membranes of nociceptors contain that allow response to noxious stimuli?

Answer 10

Receptor proteins

Question 11

What are the following receptor proteins for?
TRPV1
TRPM8
ASIC

Answer 11

Hot stimuli
Acid
Cold stimuli

Question 12

Diabetes causes peripheral neuropathy. What does this result in the lack of?

Answer 12

Pain fibres

Question 13

What are the A delta fibres for?

Answer 13

Sharp pricking fast pain (thermal and mechanical)
Precise localisation of stimulus
Reflex withdrawal

Question 14

What are the two broad classes of C fibres?

Answer 14

Peptidergic

Peptide-poor

Question 15

What are C fibres for in general?

Answer 15

Slow burning pain

Question 16

What do peptidergic C fibres release peripherally? What does this promote?

Answer 16

Peptides e.g. substance P and CGRP

Inflammatory responses and healing

Question 17

What is special about peptide-poor C fibres?

Answer 17

They have distinct receptors and projections e.g. P2X3 ATP receptors

Question 18

What type of nociception for peptidergic fibres? What type for peptide-poor fibres?

Answer 18

Thermal

Mechanical

Question 19

What are the main two lamina that A delta and C nociceptors connect to?
Which horn is this?

Answer 19

I and II

Dorsal horn

Question 20

What is NaV1.7?

What does loss of it cause?

Answer 20

A sodium channel sub-unit

Congenital indifference to pain

Question 21

What does loss of mutation of NGF receptor trkA cause?

Answer 21

Congenital insensitivity to pain with anhydrosis (CIPA) due to loss of C fibres.

Question 22

Where does the lateral spinothalamic tract end? (3) What for? Where does it not end?

Answer 22

Limbic system - subjective sensations of pain and pleasure
Reticular formation - pain-induced arousal and descending control of nociceptor input
Intralaminar (reticular) nuclei of thalamus - alerting cerebral cortex and focus of attention on pain

NOT the VPL (ventral posterolateral nucleus of the thalamus)

Question 23

The unpleasant character of pain is mediated via projections to what system?

Answer 23

Limbic

Question 24

What lamina do C fibres innervate? (3)

Answer 24

I and inter-neurons in lamina II (they also innervate lamina V through these inter-neurons)

Question 25

What lamina do A delta fibres innervate?

Answer 25

Lamina I and V projection neurons

Question 26

From where do projection neurons in lamina V receive input?

Answer 26

A beta fibres (touch) - direct input C fibres - indirect input via inter-neurons A delta fibres

Question 27

Where do axons of projection neurons decussate close to? Where do the axons travel after decussating?

Answer 27

Where the nociceptors enter the spinal cord | In the anterior spinothalamic tract (lamina V) and lateral spinothalamic tract (lamina I)

Question 28

What do projection neurons carry and to where?

Answer 28

Pain message onward from the primary afferent

Question 29

What is the anterior spinothalamic tract also known as?

Answer 29

'Neo'spinothalamic tract

Question 30

What does the anterior spinothalamic tract subserve?

Answer 30

First, discriminative aspects of pain – e.g. move arm!

Question 31

Anterior spinothalamic tract - where is the main projection to? What nuclei does it come from? What type of information does this give about the noxious stimulus?

Answer 31

Primary somatosensory cortex Ventral posterior lateral (VPL) nucleus and ventral posterior medial (VPM) nucleus Localisation & physical intensity

Question 32

What other two projections are there from the anterior spinothalamic tract? Where do they provide input to?

Answer 32

Ventral posterior inferior (VPI) nucleus - input to secondary somatosensory cortex Central lateral (CL) nucleus (reticular and limbic associated areas) - input to sites for cognitive function (prefrontal cortex and striatum) AND sites for emotion (anterior cingulate cortex)

Question 33

What is the lateral spinothalamic tract also known as?

Answer 33

'Paleo' spinothalamic tract

Question 34

What does the lateral spinothalamic tract subserve?

Answer 34

Second, punishing aspects of pain e.g. ouch, that hurts!

Question 35

What fibres innervate projection neurons in lamina I?

Answer 35

C fibres | A delta fibres

Question 36

Lateral spinothalamic tract - what nuclei are involved? (3) | Where do they project to?

Answer 36

Mediodorsal nucleus --> anterior cingulate cortex Posterior nucleus --> anterior/rostral insula Ventral medial nucleus --> anterior/rostral insula

Question 37

What collateral projections does the lateral spinothalamic tract have? (4)

Answer 37

Spinal circuitry (for reflexes) Reticular formation Periaqueductal gray Parabrachial nucleus

Question 38

What does the lateral spinothalamic tract project to the reticular formation for?

Answer 38

Arousal and alerting cortex

Question 39

What does the lateral spinothalamic tract project to the periaqueductal gray for?

Answer 39

Descending pain modulation

Question 40

Where is the parabrachial nucleus? | Where does it project to?

Answer 40

Pons | Amygdala

Question 41

What is the role of the amygdala? (2)

Answer 41

``` Limbic activation (memory) Autonomic integration and response (w/ insular cortex) ```

Question 42

What is the role of the insula? (3)

Answer 42

Interoception (detects internal regulation responses e.g. hunger) Homeostatic adjustment Emotion

Question 43

What are the four cardinal signs of inflammation?

Answer 43

Calor Rubor Dolor Tumor

Question 44

What does normal acute pain result from?

Answer 44

Nociceptor activity

Question 45

Define acute pain.

Answer 45

Acute pain is of sudden onset, usually the result of a clearly defined cause. It resolves with the healing of its underlying cause. It enables protection and facilitates healing.

Question 46

What is fast pain? | What is slow pain?

Answer 46

Fast - sharp pain conveyed by A delta fibres, elicits a reflexive withdrawal Slow - burning, lingering, emotionally charged pain

Question 47

What is peripheral sensitisation?

Answer 47

Increased sensitivity to afferent nerve stimuli. It can occur as a result of inflammation. It can cause hyperalgesia, allodynia and spontaneous pain.

Question 48

Define hyperalgesia.

Answer 48

Abnormally heightened sensitivity to pain

Question 49

Define allodynia.

Answer 49

Pain following non-noxious stimuli

Question 50

In peripheral sensitisation, due to effects of inflammatory mediators, nociceptors show reduction in ____ and increase in _____. Some nociceptors become tonically _____.

Answer 50

Activation threshold Responsiveness Active

Question 51

Prostaglandins play an key role in what type of pain?

Answer 51

Inflammatory

Question 52

What enzymes do NSAIDs target?

Answer 52

COX-1 and COX-2

Question 53

What do COX-1 and 2 use as a substrate for prostaglandin synthesis? What releases this substrate? What type of drugs target this?

Answer 53

Arachidonic acid Phospholipase A2 Steroids

Question 54

COX-1 is present in tissue at ___ levels | COX-2 is induced during _____

Answer 54

Low | Inflammation

Question 55

How do prostaglanadins sensitise C fibres? (2)

Answer 55

Increasing numbers of other receptors | Increasing the number of open sodium channels

Question 56

Prolonged nociceptor input produces an increase in excitability of... This causes modified responsiveness.

Answer 56

Dorsal horn projection

Question 57

Describe central sensitisation.

Answer 57

There are enhanced responses and even low level inputs produce responses. It causes pain - allodynia, secondary hyperalgesia and spontaneous pain. It differs from peripheral sensitisation as it extends outside the region of flare.

Question 58

What is flare due to?

Answer 58

Release of peptides by C-fibres and other local inflammatory mediators

Question 59

How many weeks does pain have to last for it to be classified as chronic?

Answer 59

12 weeks

Question 60

What does maladaptive mean in terms of pain?

Answer 60

It continues past the healing phase following an injury

Question 61

Chronic pain is normally associated with an underlying condition/arises from nociceptive pain? - True or False

Answer 61

True

Question 62

Maladaptive pain is due to...?

Answer 62

Abnormal activity in the neural system

Question 63

Are normal analgesics effect for maladaptive pain?

Answer 63

No

Question 64

How is maladaptive pain treated? Does it respond well to treatment?

Answer 64

Anticonvulsants Anti-depressants No - often resistant to treatment

Question 65

What is neuropathic pain due to?

Answer 65

Injury/dysfunction in PNS or CNS

Question 66

What is dysfunctional pain due to? | What is it characterised by?

Answer 66

No known lesion or inflammation | Hyperalgesia, allodynia, spontaneous pain

Question 67

Where does pain modulation occur? (4)

Answer 67

Cortex From the brain/brainstem Spinal cord (central sensitisation) Periphery (inflammation)

Question 68

Where does endogenous modulation occur?

Answer 68

At the spinal cord level

Question 69

Superior parietal cortex – insula – amygdala path is for...?

Answer 69

Cognitive/attention control/intensity of pain

Question 70

Anterior cingulate cortex – pre-frontal cortex – periaqueductal gray path is for...? What drug is it sensitive to?

Answer 70

Emotion/unpleasantness | Naloxone

Question 71

What fibres does acupuncture activate? | What pathway does it work through?

Answer 71

Aδ fibres | Periaqueductal gray mediated control

Question 72

What is the basis of the TENS (transcutaneous electrical nerve stimulation) machine?

Answer 72

Stimulation of non-noxious afferents (or mildly noxious afferents) - these stimulate lamina II inter-neurons.