Neurobiology of Pain

Question 1

explain the process of nociception

Answer 1

Triggered by actual or potential tissue damage

Detected and turned into action potential by receptors -> nociceptors are usually FREE NERVE ENDINGS in tissue

Question 2

Explain Cutaneous Nociception. What kind of pain is experienced

Answer 2

Arises from the skin, caused by damage/irritation of free nerve endings. Results in a SHARP and LOCALISED Pain.

Question 3

Explain deep somatic nociception

Answer 3

Muscles, periosteum, tendons. Caused by pressure, ischaemia, tissue damage. Resultant pain is diffuse and radiating

Question 4

What are the three classes of nociceptor

Answer 4

Thermal
Mechanical: sharp, pricking
Polymodal: most tissues, variety of stimuli (mechanical damage, chemical distress, thermo)

Question 5

What receptor type detects noxious heat, cold and noxious mechanical stimuli?

Answer 5

Tranisent Receptor Potential Family detect noxious heat (TRPV1), cold (TRPM8) and mechanical (TRPA1) stimuli
Also ASICS (acid sensitive ion channels)- > chemosensitive
Ca+, NA+ , K+ channels regulate thresholds

Question 6

Visceral nociceptors- where are the cell bodies?

Answer 6

DRG and the nodose ganglion (for vagal afferents). Similar fibre type and spinal cord targets - eg. nucleus of solitary tract.

Question 7

What do A-delta nociceptor fibres do?

What are the subtypes and what is the ‘first pain’ associated?

Answer 7

A delta nociceptor fibres produce sharp pricking pain from mechanical and fast thermal nocicpetors. Myelinated, speeds 3-10ms. Go to ventrobasal and posterio thalamic nuclei. Use GLUTAMATE as NT
TYPE I: First pain mechanical
TYPE 2: Low head threshold, first pain thermal

Question 8

What do Somatic C fibre nocicpetors do?

Answer 8

Somatic C fibres produce a DULL, BURNING, ACHING sensation.
Unmyelinated travel at 0.5-2ms.
Use substance P (neuokinin 1 receptors), CGRP (calcitonin geene related peptide)
Most go to- ascending activated nuclei in brainstem.
DISTRESSING PAIN

Question 9

Describe peripheral sensitisation

Answer 9

= lowering of nociceptor threshold -> ie. more stimulus transduction.

Question 10

define hyperalgesia

Answer 10

increased subjective response to the same nociceptive stimulus.

Question 11

Describe ‘ Silent’ viceral nociceptors

Answer 11

C-fibre nocicpeptors which awaken after inflamamtion or other triggering events. Respond only to inflammaton.
40-50% of total afferent innervation of bladder, bowel

Question 12

Describe th proinflammatory signals occuring in peripheral sensitisation

Answer 12

Platelet activating factor, prostaglandins, leukotrienes, substancce P/CGRP
Also local mast cell reactions
Nerve inflammation causes interleukkin release

Question 13

What is central sensitisation

Answer 13

Increased excitability of CNS nociceptive relay neurons. this is driven by (1) increased signalling from nociceptor (2) changes in desceniding modulation (3) environment

Question 14

Allodynia and Neuropathic pain are examples of central sensitisation. Explain

Answer 14

Allodynia: perception of non noxious stimuli as painful.

Persists beyond initial stimulus.

Question 15

Spinal Cord Sensitisation:

Name the Fast Pathway & Slow pathway

Answer 15

A-delta is fast pathway: NMDA receptors- change synaptic plasticity
Slow pathway: substance P, somatic C fibres, CGRP, growth factors.
Chloride shifts: alter resting postential, effects of glycine and GABA
GABAergic, glycinergic disinhibition
Microglia: inflammatory signalling

Question 16

Describe the pathway for forebrain analysis of pain

Answer 16

Nociceptors -> interneurons -> spinothalamic tracts -> thalamus -> SSC also to amygdala, cingulate and insular cortex

Question 17

Describe the descending modulatio of nociception

Answer 17

Ascending pathways are influenced byt he descending pain modulatory system:
PAG - activated by OPIOIDS via the mui opioid receptor (MOR). PAG controls RVM which regulates nocicpetor transmission into the spinal cord.
RVM (rostral ventral medulla)
Release NA and Serotonin onto spinal nocicpetor processing circuits. NA is inhibitory to nociception versus serotonin which can be inhibitory or excitatory.

Question 18

What are some of the forebrain structures which process pain?

Answer 18

• EMOTION: prefrontal, cingulate, insular cortex
• SENSATION: SSC & thalamus
• EMOTION, ALARM, SALIENCE: Amygdala
• ANTICIPATION: Hippocampus
• SURVIVAL THREAT: hypothalamus
• Reward systems

Question 19

What are the components of pain

Answer 19

• Irritation or damage to tissue
• Transduction of noxious stimuli
• Detection by a receptor (action potential)
• Transmission of nociception: : : synapses (glutamate, substance P), interaction with other sensory inputs (dorsal horn of spinal cord), tracts, nuclei, relays, thalamic nuclei
• Perception based on mental state