Lecture 5.1 The Neural Basis of Pain and Analgesia

Question 1

What is Nociception?

Answer 1

Non-conscious neural traffic in response to (potential) trauma

Question 2

What is Pain?

Answer 2

Complex and unpleasant awareness of a sensation

Question 3

What Factors influence Pain? (7)

Answer 3

• Experience
• Expectation
• Context
• Culture
• Mood
• Cognitive Set
• Injury

Question 4

What is IASP definition of Pain?

Answer 4

An unpleasant sensory and emotional experience associated with actual or potential tissue damage

Question 5

What is the link between pain and nociception?

Answer 5

• Nociception leads to pain
• But pain isn’t only nociception

Question 6

What is the Neural basis of Pain?

Answer 6

• Unclear

Question 7

What parts of the brain are though to be involved in the Neural basis of Pain? (5)

Answer 7

• Ascending & Descending Pathways
• Somatosensory Cortex – perception of pain
• Amygdala – fear
• Hippocampus – memories
• Prefrontal Cortex – planning and reaction

Question 8

How do Pain Receptors (Nociceptors) work?

Answer 8

• Free nerve endings sensitive to mechanical, thermal,
  and/or chemical stimulation
• Contain TRP channels (cation channels)

Question 9

What can trigger TRP channels? (5)

Answer 9

• Inflammation
• Injury
• Nerve invasion e.g. cancer
• Injury to CNS
• Abnormal activity (eg chronic regonal pain syndrome)

Question 10

What do the Spinothalamic Tracts detect? (3)

Answer 10

• Pain
• Temperature
• Crude Touch
• Carries information from the skin to the thalamus
  where it is processed and transmitted to the primary
  sensory cortex

Question 11

What fibres is pain is transmitted via? (2)

Answer 11

and C Fibres

Question 12

What is the structure and function of Aδ Fibres?

Answer 12

• Myelinated
• Transmit fast, sharp, well localised pain

Question 13

What is the structure and function of C Fibres?

Answer 13

• Unmyelinated
• Transmit slow, diffuse, dull pain

Question 14

What is Visceral/Organ Pain?

Answer 14

• It is diffused and poorly localised
• Organs have relatively few pain sensors
• Enter spinal cord at multiple levels
• No cortical mapping
• Referred pain

Question 15

Modulation of Pain: Spinal Cord (1)

Answer 15

Gate Theory of Pain

Question 16

Modulation of Pain: Central (2)

Answer 16

• Endogenous neuromodulatory systems (opioids,
  endocannabinoids) in brain and spinal cord
• Central modulation/descending signals from the brain

Question 17

What is the Gate Theory of Pain?

Answer 17

• Modulation of nociception at the spinal level in the
  substantia gelatinosa of the dorsal horn
• Rubbing a painful area reduces the sensation of pain =
  Gate Theory
• The touch pathway neurons– activate an inhibitory
  neuron reducing ascending pain signals

Question 18

What does PAG stand for?

Answer 18

Periaqueductal Grey

Question 19

What does RVM stand for?

Answer 19

Rostroventromedial Medulla

Question 20

Central Modulation of Pain

Answer 20

Descending analgesia producing pathways descend from the brain stem to the spinal cord

Question 21

What is Chronic Pain?

Answer 21

Any pain that lasts for more that 3 months past the normal healing time for an injury or disease

Question 22

What is Hyperalgesia?

Answer 22

A stimulus that would normally be perceived as slightly painful is perceived as significantly more so

Question 23

What does increased excitability of neurones in the dorsal horn of the spinal cord lead to?

Answer 23

It leads to allodynia, perception of pain from something that is normally an innocuous stimulus

Question 24

What is Neuropathic Pain?

Answer 24

Pain caused by a lesion or disease of the somatosensory nervous system

Question 25

What can cause Neuropathic Pain? (6)

Answer 25

• Cancer
• Post Herpetic Neuralgia
• Phantom Limb
• Diabetes
• MS
• Spinal Injury

Question 26

What can cause Neuropathic Pain on a Thalamic/Cortical Level? (3)

Answer 26

• Infarctions
• Tumours
• Multiple Sclerosis

Question 27

What can cause Neuropathic Pain on a Brainstem Level? (3)

Answer 27

• Infarctions (Wallenberg’s Syndrome),
• Tumours
• Multiple Sclerosis

Question 28

What can cause Neuropathic Pain on a Spinal Level? (2)

Answer 28

• Spinal Cord Injuries
• Multiple Sclerosis

Question 29

What can cause Neuropathic Pain on a Peripheral Level? (5)

Answer 29

• Diabetic Neuropathies
• Peripheral Trauma
• Plexus Avulsion
• Dorsal Rhizotomy
• Herpes Zoster

Question 30

After a peripheral nerve injury sensitisation occurs it can lead to….? (7)

Answer 30

• Decreased threshold of the nociceptor to activation
• Increased receptive field of nociceptors
• Allodynia
• Hyperalgesia
• Hyperpathia
• Emergence of spontaneous activity / increased
  excitability
• Damaged peripheral nerves develop abnormal sodium
  channels which fire dysfunctionally and demonstrate
  different depolarisation properties

Question 31

What is Hyperpathia?

Answer 31

Prolonged post stimulus sensations

Question 32

Symptoms of Neuropathic Pain (3)

Answer 32

• Shooting and Burning Sensation
• Tingling and Numbness
• Unpredictable

Question 33

Treatment of Neuropathic Pain (4)

Answer 33

Offer a choice of amitriptyline, duloxetine, gabapentin or pregabalin as initial treatment for neuropathic pain

Question 34

Types of Analgesia (5)

Answer 34

• Paracetamol
• NSAIDS
• Opioids
• Adjuvants
• Placebo

Question 35

WHO Analgesic Ladder (3)

Answer 35

• Step 1: Non-Opioids
• Step 2: Weak Opioids
• Step 3: Strong Opioids
• Ajduvants

Question 36

Examples of Non-Opioids (2)

Answer 36

• Paracetamol
• NSAIDs – ibuprofen, diclofenac, naproxen

Question 37

Examples of Weak Opioids (2)

Answer 37

• Codeine
• Tramadol

Question 38

Examples of Strong Opioids (4)

Answer 38

• Morphine
• Diamorphine
• Fentanyl
• Alfentanyl

Question 39

Examples of Adjuvants (9)

Answer 39

• Antidepressants
• Anticonvulsants
• Antispasmodics
• Steroids
• Muscle Relaxants
• Local Anaesthetics
• Bisphosphonates
• Radiotherapy
• Nitrous Oxide

Question 40

Non-Pharmacological ways to manage Pain (6)

Answer 40

• TENS
• CBT
• Meditation
• Acupuncture
• Massage
• Hypnosis

Question 41

What Opioid Receptors are there? (3)

Answer 41

• µ (mu)
• δ (delta)
• ƙ (kappa)

Question 42

What Opioid Receptors is Codeine an agonist to?

Answer 42

Partial/weak (µ) mu-opioid receptor agonist

Question 43

What Opioid Receptors is Morphine an agonist to?

Answer 43

Full agonist at mu-opioid receptors in the CNS

Question 44

How does Morphine work?

Answer 44

• Bind receptors in regions of the CNS involved in
  transmission and modulation of pain
• Dampen nerve signals transmitting pain

Question 45

Side-Effects of Opioid use (10)

Answer 45

• Euphoria
• Sedation
• Respiratory Depression
• Tolerance
• Miosis
• Nausea & Vomiting
• Cough Suppression
• Constipation
• Dependence
• Addiction

Question 46

How do Cannabinoids work?

Answer 46

• Cannabinoids inhibit excitatory synaptic transmission
  in substantia gelatinosa cells
• Cannabinoid (CB1) receptors are expressed
  presynaptically, where they inhibit transmitter release
  from nociceptive primary sensory neurones
• Cannabinoids act to reduce experimental models of
  pain – non-opiate based analgesia

Question 47

How is Acupuncture theorised to work?

Answer 47

• Acupuncture involves the insertion of extremely fine
  needles into the skin at specific acupoints
• This may relieve pain by releasing endorphins, the
  body’s natural pain-killing chemicals
• They also affect the part of the brain that governs
  serotonin, a brain chemical involved with mood