7.5 Pain pathways and modulation

Question 1

What are the dimensions of pain?

Answer 1

Discriminative: tells us where it hurts
Affective: how it makes you feel
Motivational: what you will physically do to respond
Cognitive/evaluative: appraisal, cultural values etc.

Multidimensional pain means that a response requires different pain regions

Question 2

What is hyperalgesia and allodynia?

Answer 2

Hyperalgesia: augmented sensations of pain from noxious stimuli
Allodynia: pain from innocuous stimuli

Question 3

What is neuropathic and neurogenic pain and what is an example of each?

Answer 3

Neuropathic: pain that occurs in the absence of nociceptor stimulation (phantom limb)
Neurogenic: occurs due to primary damage of the NS (carpal tunnel)

Question 4

What are the different kinds of receptors and what do they respond to?

Answer 4

Nociceptors: tissue damage/thermal stimuli
Mechanical nociceptors: strong sitmuli such as pinch and sharp objects
Thermal nociceptors: noxious hot and cold
Chemical: irritants such as histamine, capsaicin, mustard oil
C-polymodal: most common, activated by noxious mechanical, heat, cold and irritant chemicals

Question 5

What pain is transmitted via A and C fibres

Answer 5

A: acute, sharp or pricking pain
C: slow, dull, burning pain

Question 6

What receptor channels are involved with noxious heat, mechanical and chemical irritants?

Answer 6

Noxious heat: transient receptor potential (TRP) V1
Mechanical: TRPV2 and TRPA1
Chemical: TRPA3 for mustards, garlic and volatile irritants, ASIC3 for muscle and cardiac pain

Question 7

What effect does bradykinin have?

Answer 7

Depolarises nociceptors as well as stimulates long lasting intracellular changes making heat activated ion channels more sensitive

Question 8

What effect does prostaglandins have?

Answer 8

generated by lipid membrane breakdown and increases nociceptor sensitivity

Question 9

What effect does substance P have?

Answer 9

a peptide produced by nociceptors causing vasodilation of adjacent capillaries and the release of histamine from mast cells

Question 10

What effect does histamine have?

Answer 10

Released by mast cells that increases the excitability of the nerve ending membrane

Question 11

What are the substances released in response to injury?

Answer 11

Bradykinin
Prostaglandins
Substance P
Histamine

Question 12

What is neurogenic inflammation?

Answer 12

peripheral mechanism whereby inflammation is caused by the liberation of chemical mediators released from peripheral nerve terminals

Question 13

What ares of the brain make up the pain matrix?

Answer 13

Somatosensory cortex (discriminative)
Insular cortex (interoceptive)
Amygdala (fear component)
Anterior cingulate gyrus (affective)

Question 14

Where does pain discrimination occur and how does it get there?

Answer 14

Occurs in the somatosensory cortex (S1 and S2) via the ventral posterior nucleus of the thalamus

Question 15

How does pain in the face/head/meninges get discriminated?

Answer 15

Ascend/descend along spinal trigeminal tract to brainstem
Afferents synapse on the trigeminal nucleus
Axons cross the midline to form the trigeminothalamic tract
This joins the medial lemniscus
Fibres synapse onto the VPM thalamus which will project to the face regions of S1

Question 16

What does the amygdala control in pain?

Answer 16

Conditioned fear memory

Question 17

What does the hypothalamus do?

Answer 17

autonomic NS regulation

Question 18

What does the periaqueductal grey do?

Answer 18

Region where behaviour, autonomic NA and pain regulation responses are orchestrated

Question 19

What does the superior colliculus do?

Answer 19

Head orientating reflex

Question 20

What does the reticular formation do?

Answer 20

Arousal

Question 21

What is the role of the spinoreticular pathway?

Answer 21

Responsible for arousal and alerts the CNS to a painful event
Will give rise to the reticulosponal projections which will contribute to the control of pain

Question 22

What is the spinomesencephalic pathway?

Answer 22

Information comes in from the spinal cord to the periaqueductal grey, this projects to the amygdala (pathway for emotional response), to the hypothalamus (orchestrating autonomic response) and to medullary raphe for analgesia

Question 23

What is the function of the spinomesencephalic pathway?

Answer 23

Responsible for the coordination of behavioural, emotional and autonomic components, as well as pain modulation to a noxious stimuli

Question 24

What does the anterior cingulate gyrus do?

Answer 24

Provide the affective/motivational aspects to pain

• emotional response
• Unpleasantness

Question 25

What does the insular cortex do?

Answer 25

Interoceptive aspects of pain

Question 26

What is the role of the midline thalamic nuclei?

Answer 26

Relay nuclei to the cingulate and insular cortex

Question 27

How does visceral afferet information travel and what kind of signals?

Answer 27

Afferent pain information via sympathetic pathways (spinothalamic)
Afferent signals for reflex control and homeostasis via parasympathetic pathways

Question 28

What is referred pain thought to be from?

Answer 28

The cross talk between inputs nociceptive inputs from viscera result from in the activation of cells normally carrying cutaneous information, resulting in pain perceived in those dermatomes

Question 29

Where are the 3 synapses of the dorsal column system?

Answer 29

1. Lamina X
2. Gracile and cuneate nucleus
3. VP thalamus

Question 30

What is peripheral sensitisation?

Answer 30

Increased excitability at nerve endings, usually due to inflammation

Question 31

What are the neuronal elements of sensitisation?

Answer 31

Substance P, clacitonin gene-related peptide and ATP which leads to vasodilation, swelling and release of histamine from mast cells

Question 32

What is the gate control theory of pain?

Answer 32

Non nociceptive inputs can lead to the masking of pain

Question 33

What is central sensitisation?

Answer 33

Increase in the excitability of neurons centrally which results in transmission of nociceptive signals elicited by sub-threshold activation of nociceptive afferents

Question 34

What causes central sensitisation?

Answer 34

Increased ion channels and receptors
Long term potentiation
reorganisation after a sprouting onto STT neurons
Windup: constant stimulation of a fixed intensity
Reduced GABA/gly activity in dorsal horn
Microglia and astrocytes which release inflammatory modulators

Question 35

What is the normal course of central sensitisation?

Answer 35

Usually it will revert back to normal after the injury has gone but in some cases it can progress into neuropathic pain

Question 36

What plays the central role in descending modulation of pain?

Answer 36

PAG - will act on various sites in the dorsal horn such as synaptic terminals of afferents, excitatory/inhibitory interneurons, synaptic terminals of descending projections, directly onto STT cells

Question 37

What are the opioid receptors and what targets them?

Answer 37

MU (1-3): endorphins and enkaphalins
Delta (1,2): endorphins and enkaphalins
Kappa (1-3): dynoprphins

Question 38

What is the main target of morphine and where is it found?

Answer 38

MU receptors - mainly presynaptic and found in the dorsal horn and PAG but also in other brain regions (nucleus accumbens, amygdala and Cx)

Question 39

What are the pre and post synaptic effects of opioids?

Answer 39

Pre: inhibits voltage gated Ca channels to reduce transmitter release
Post: increase K conductance to hyperpolarise the membrane

Question 40

What is the role of exogenous cannabinoids?

Answer 40

Suppress nociceptive neurons in the dorsal horn

Question 41

How do endocannabinoids work?

Answer 41

Cannabinoid receptors are G protein coupled and activation of CB1 inhibits adenylate cyclase and calcium channels, activates K channels inhibiting synaptic transmission

In the spinal cord they prevent the release of presynaptic NTs

Question 42

How is analgesic effect on the PAG blocked?

Answer 42

CB1 receptor antagonists