Pain pathways

Question 1

Opioids activate descending pathways that inhibit pain transmission by acting on neurons in which region?

Answer 1

Periaquedactal grey matter (PAG)

Question 2

Transmitters in pain control system(s) include which neurotransmitters

Answer 2

Dopamine

Question 3

When/ what can activate then pain control system?

Answer 3

It can be activated by touch

Question 4

What are Abeta fibres?

Answer 4

Myelinated fibres for transmission of low intensity stimuli (touch, brush)

Question 5

What are Adelta fibres?

Answer 5

Myelinated fibres for transmission of sharp sensation/acute pain

Question 6

What are C-fibres?

Answer 6

Unmyelinated fibred, conducts slow pains/aches

Tissue damaging stimulation from deeper tissue layers i.e. muscle

Question 7

What is neuropathic pain and list some potential causes?

Answer 7

Neuropathic pain : induced by lesions of the somatosensory CNS

Potential causes: 
SCI 
Diabetic neuropathy
Stroke 
Viral infections (Herpes virus, HIV)

Question 8

List potential drug classes that could be used for neuropathic pain. Briefly explain the mechanism

Answer 8

Tricyclic antidepressants: Inhibit noradrenaline and serotonin re-uptake

Pregabalin & Gabapentin : Inhibit L type voltage gated Calcium channels (bind to alpha2subunit)

Question 9

Give examples of different types of pain

Answer 9

Acute Pain 
Inflammatory pain 
Neuropathic pain 
Musculoskeletal pain
Physiological pain (acute)

Question 10

What is the difference between allodynia and hyperalgesia?

Answer 10

Allodynia is pain evoked by non-noxious stimuli

Hyperalgesia is pain evoked by noxious stimuli

Question 11

Briefly explain transmission of pain to the brain

Answer 11

1- Peripheral nociceptors detect pain at nerve endings

2- Action potential is triggered

3-This is propagated to the dorsal horn of SC.(neurotransmitters are released)

4- Ascending neurons are activated

5- Pain info is transmitted to the brain (Thalamus –> sensory cortex)

Question 12

What class of receptor type are opioid receptors?

Answer 12

GPCRs

Question 13

What occurs at the dorsal horn of SC when an action potential is triggered?

Answer 13

2 neurotransmitters are releaased:
Substance P : activates tachykinin
Glutamate : acts on NMDS receptors

Sends pain info up to the brain

Question 14

Which endogenous neurotransmitter inhibits the release of glutamate?

Answer 14

Endorphins

Question 15

What do periphery sensory nerves respond to? (Stimulus)

Answer 15

Temperature: Heat/cold 
Mechanical stimulation 
Chemical stimulation (Capsaicin, acid)

Question 16

Give 4 examples of mediators generated from tissue damage.

Answer 16

Bradykinin,
5HT
Nerve growth factor
Inflammatory mediators (cytokines, histamine)

Question 17

List mechanoreceptor fibres

Answer 17

Abeta fibres
Adelta fibres
C fibres

Question 18

List Nociceptor fibres

Answer 18

Adelta fibres

C fibres

Question 19

List Thermoreceptor fibres

Answer 19

C fibres

Question 20

What neurotransmitters/compounds inhibit the release of glutamate at the pre-synaptic receptors (in dorsal horn (Cfibres) )?

Answer 20

Opioids
GABA
Noradrenaline
Endorphins

Question 21

What is the gate control theory of pain?

Answer 21

Non-painful input closes the nerve “gate” to painful input.

Preventing pain sensation from travelling to the CNS

Question 22

What is TENS?

Answer 22

Transcutaneous electrical nerve stimulation

Question 23

Briefly explain the descending control system.

Answer 23

Opioid excite the PAG & NRGP neurons –> this stimulates neurons in the Raphe nucleus (NRM)

5HT and enkephalin neurons of the NRM (go down to the dorsal horn) inhibit the pain transmission

Question 24

Which endogenous neurotransmitters inhibit pain and how?

Answer 24

5HT and enkephalins in the NRM inhibit pain at the dorsal horn

Noradrenergic neurons (of locus coerulus) inhibit pain at the dorsal horn

Question 25

Discuss inflammatory pain

Answer 25

Inflammatory mediators released (5HT, histamine, interleukins, bradykinin)

Acts on peripheral nerve endings

Depolarises neuron –> sends pain info

Question 26

Discuss neuropathic pain (briefly)

Answer 26

1 -Activation (Hypersensitivity due to increased Na channels)

2-Modulation (Phosphorylatyion of NMDA receptors = more sensitive to glutamate)

3-Modification (Bipolar nerves start changing gene expression –> leads to neuronal death –> NMDA exocitotoxicity)

Question 27

What mechanism better describes morphine tolerance?

Answer 27

Recruitment of G receptor kinases to the mu- opioid receptor

Question 28

What pathway does pain travel through to get from the periphery to the brain?

Answer 28

Spinothalamic tract