Neural basis of pain.

Question 1

What is pain?

Answer 1

An unpleasant sensation and emotional experience with actual or potential tissue damage

It has visceral and somatic origin
Elicits sensation with autonomic, somatic, endocrine and emotional responses

(So it is both sensory - discriminative - and subjective - affective, behavioural processes)

Question 2

Define nociception

Answer 2

Non-conscious neural traffic originating with trauma or potential trauma tissue

Question 3

What is the difference between threshold for pain and tolerance to pain?

Answer 3

Stimulus threshold
- Is the same in each of us

Tolerance
- Is our variable reaction to a painful stimulus
(environment, situation, psychological/emotional factors, increases with age, ongoing pain, placebo effect)

Question 4

What tracts are used for pain?

Answer 4

Anterolateral system

• Spinothalamic tract is the only conscious pain pathway
• Lateral spinothalamic tract is pain

There is also the routes to the Cerebellum that transmit pain, but that is unconscious

Question 5

What are the two different type of pain sensations in terms of time cale?

Answer 5

Direct (fast) lateral STT

• Discriminative pain (quality, intensity, location)
• Somatotopic organization
• Contralateral
• No sub-cortical target
• Cortical locatin - Parietal lobe
• Other functions of temperature and crude touch
• Dorsal horn origin of lamina I, IV, V

Indirect (slow) Lateral STT
- Affective - arousal
- Bilateral
- Synapses in brain
- Sub-cortical targets - hypothalamus, RF, limbic
structures, autonomic centres.
- Dorsal horn origin - Lamina I, IV and V (VII,VIII)

Question 6

Name the indirect pathways of pain sensation.

What sensations are they responsible for?

Answer 6

Spinoreticular fibres
- Arousal, wakefulness
Spinomesencephalic fibres
- Contributes to activation of descending pain inhibition
- Emotion
Spinotectal fibres
- Reflex eye, upper body and head turning
Spinoghypothalamic fibres
- Autonomic and reflex responses

Question 7

What are the stages of nociception?

Answer 7

Transduction
- Activation of nociceptors by a stimulus
Transmission
- Relay of action potentials along nociceptive fibres to
CNS
Modulation
- By other peripheral nerves or CNS mechanisms
Perception (where pain is felt)
- The interpretation by the brain of the sensation as
painful

Question 8

What are the two different types of nociceptors?

Answer 8

A-delta
- Mechanical
C
- Mechanical 
- Thermal
- Chemical

Question 9

What are some analgesics acting at site of injury?

Answer 9

NSAID

Steroids

Question 10

What are some of the things that happen in transduction of a pain stimulus?

Answer 10

A lesion of the skin would then:
- Cause increases of K+, prostaglandin, serotonin and
bradykinin levels, thus activating nociceptor.
- Substance P is the released from nerve endings,
increasing capillary permeability and contributing to
inflammation.
- Substance P also causes mast cells to release
histamine, which in turn activates nociceptor endings

Question 11

Tell me about the two types of nociceptive fibres.

Answer 11

A-delta
Sharp, stabbing pain
Well localized
First pain / phase 1
Lower threshold
Initiates withdrawal reflex

C
Dull, throbbing pain
Poorly localised
Second pain / phase 2
Higher threshold
Tissue damage occurring

Question 12

How do local anaesthetics work? (Very simple)

Answer 12

They inhibit voltage dependant sodium channel activity, thereby stopping the propagation of an action potential along a nociceptive fibre

Question 13

Where do nociceptive afferents terminate in the spinal cord?

Answer 13

A-delta fibres to I and V
C fibres to I, II(substantia gelatinosa) and V

(A-beta branches to II, IV and V)

STT origin in I, IV to VII

Question 14

How does visceral and referred pain work?

Answer 14

Visceral fibres converge on the same second order neurones shared by somatic nociceptive fibres (lamina V)

Question 15

What is analgesia?

Answer 15

Inability to perceive pain when tissue damage is occurring

Can be caused by:
Hypnosis
Morphine
TENS
Natural childbirth techniques
Placebos

Question 16

Describe central modulation.

Answer 16

Inherent modulatory system via inhibition in spinal cord

1. The gate control theory of pain
   - Could be how massages, TENS and acupuncture work
2. Central and descending spinal system, employing endogenous opioid peptide analgesics and other neurotransmitters

Question 17

Name some endogenous analgesics.

Answer 17

Opioid neuropeptides:
Enkaphalins, endorphins, dynorphins, endomorphins

Opiate receptors: μ(mu), delta, k(kappa) and nociception
Agonist: Morphine codeine, heroin
Antagonist: Naloxone

Question 18

What are the different pathways of central modulation of pain?

Answer 18

Pain fibres synapse in the dorsal horn of the spine
Then they travel up and act on both the thalamus (Direct pathway) and nucleus reticularis paragigantocellularis (NRPG)

The thalamus then has fibres to the cortex (direct) and some excitatory fibres to periaqueductal grey matter
The cortex has inhibition and excitatory pathways to the periaqueductal grey matter
This then has excitatory fibre to the nucleus raphe magnus (NRM)
Which has inhibitory fibres to the dorsal horn to reduce pain

The pathway to the NRPG then has excitatory to the NRM as well

There is also fibres from the hypothalamus to:

• Periaqueductal grey matter
• Locus ceruleus

Locus ceruleus the has inhibitory fibres to the dorsal horn

Question 19

What are some other transmitters for pain analgesia or therapies in that area?

Answer 19

Analgesia in morphine tolerant patients:
- Baclofen (GABA agonist), anti-depressants, anti-
convulsants
- Somatostatin

Potential drug therapies:
- NMDA receptors, ion channels, neurotrophins (NGF)

Question 20

How are the thalamus and cortex involved in perception of pain?

Answer 20

Thalamocortical projections carry information on location intensity and nature of pain.

Primary and association areas, secondary somatosensory cortex

Emotional response via the limbic system
Stress response via hypothalamus