Pain

Question 1

What are the pain axons in the brain?

Answer 1

A delta mylenated axons 20 m/s
C fibre unmyelinated 2 m/s

Question 2

What are the pain receptors in the brain?

Answer 2

Nociceptors = pain receptors

A delta mechanosensitive
A delta mechanothermal
Polymodal nociceptors associated with me C fibres

Question 3

How can you experimentally demonstrate that nociception involves specialised neurons?

Answer 3

Peripheral axons responsive to nonpainful mechanical or thermal stimuli do not discharge at a greater rate when painful stimuli are delivered to the same region of the skin surface

The nociceptor axons begin to discharge only when the strength of the stimulus reaches high levels

At the same stimulus intensity, other thermoreceptors discharge at a rate no different from the maximum rate already achieved within the nonpainful temperature range, indicating the presence of both nociceptive and non-nociceptive thermoreceptors

Question 4

What are the two categories of pain perception?

Answer 4

A sharp first pain
Delayed and longer-lasting second pain

Question 5

What is responsible for each type of pain sensation?

Answer 5

First pain = A delta fibres
Second pain = increase the stimulus intensity further to activate the C fibres

Question 6

How are we able to confirm which fibres are responsible for which pain sensation?

Answer 6

It is possible to anesthetise C fibres and A delta fibres

The selective blocking experiments that A delta fibres are responsible for first pain and C fibres are responsible for second pain

Question 7

What is Capsaicin?

Answer 7

Chemical in chillis which causes heat or a burning sensation

Question 8

How does Capsaicin work?

Answer 8

Capsaicin activates responses in polymodal nociceptiors (a subset of nociceptive C fibres) by opening ligand-gated ion channels that permit entry of Na+ and Ca2+

Capsaicin binds to vanilliod receptors (VR1 and TRPV1) and vanilliod like receptors causing the receptor channel to open causing depolarisation of the cell

The binding of capsaicin produces similar sensations to those of excessive heat or abrasive damage explaining why when eating a chilli you get sensations of burning

Question 9

Why is chilli so hard to get rid of?

Answer 9

It is lipid permeable and water soluble, so it goes through the lipid bi-layer and has a special binding site within the receptor on the inside of the neuron

Question 10

What is the major pathway for discriminative aspects of pain and temperature sensation?

Answer 10

Spinothalamic tract and Trigeminothalamic tract (pain and temp from the face)

Question 11

Explain the spinothalamic tract

Answer 11

Pain and temperature from the body is detected from nociceptors in the skin
Signals pass trough the dorsal root ganglion and enter the spinal cord

Ascend or descend one or two vertebral levels via Lissauer’s tract and then synapse with secondary neurons in the grey matter before decussating to the other side of the spinal cord

Axons travel up the length of the spinal cord into the brainstem and then synapse with 3rd order neurons in the ventral posterior lateral nucleus of the thalamus. From here, the signals to the primary somatosensory cortex

Question 12

What is the difference between the spinothalamic tract and the dorsal medial lemniscus pathway?

Answer 12

Spinothalamic tract is contralateral = decussates in the spinal cord and then ascends

Dorsal medial lemniscus pathway ascends in the ipsilateral dorsal column = doesn’t decussate until medulla

Question 13

What is visceral pain?

Answer 13

Pain related to the internal organs in the midline of the body

Question 14

How can you locate a spinal cord lesion?

Answer 14

As the dorsal medial lemniscus pathway travels ipsilateral up the spinal cord and the spinothalamic tract travels contralaterally, you can tell where abouts the lesion is depending on the symptoms
Loss of sensation of touch, pressure, vibration and proprioception in the ipsilateral side to the lesion
Deficits of pain and temperature perception on the contralateral side to the lesion
This is referred to as dissociated sensory loss and can be used to define the level of the lesion

Question 15

What is the pathway for visceral pain?

Answer 15

The dorsal column pathway - not viewed as a pathway involved in pain perception but compelling evidence has implicated its role in relaying visceral nociceptive information

1. Primary visceral afferents enter the spinal cord and synapse on the dorsal root ganglion
2. Ascend to the dorsal column nuclei (cuneate/gracile fasciculus)
3. Decussate across the medulla then ascend to the VPL nucleus of the thalamus
4. Project to the insular cortex

Question 16

What is referred pain?

Answer 16

Few if any neurons in the dorsal horn of the spinal cord are specialised solely for the transmission of visceral pain
It is conveyed centrally via dorsal horn neurons that may also convey cutaneous pain
A patient may therefore present to a physician with the complaints of pain at a site other than its actual source - this is called referred pain

Question 17

Describe the dorsal column pathway for visceral pain

Answer 17

Signals sent to the dorsal root ganglion into the spinal cord
Travel up to the cuneate nucleus and then decussate across the medulla before ascending to the thalamus and then to the insular cortex

Question 18

What evidence supports the idea that the dorsal column visceral sensory projection is the principal pathway by which painful sensations in the viscera are detected?

Answer 18

1. Neurons in the ventral posterior lateral nucleus, gracile nucleus and near the central canal of the spinal cord all respond to noxious visceral stimulation
2. Responses of neurons in the ventral posterior lateral nucleus and gracile nucleus to such stimulation are greatly reduced by spinal lesions of the dorsal columns
3. Infusion of drugs that block nociceptive synaptic transmission into the intermediate gray region of the sacral spinal cord blocks the responses of neurons in the gracile nucleus to noxious visceral stimulation

Question 19

What is midline myelotomy?

Answer 19

Surgical transection of the axons that run in the medial part of the dorsal columns

= Causes significant relief from debilitating pain that can result from visceral cancers

Question 20

What is affective-motivational pain?

Answer 20

The unpleasant feeling, the fear and anxiety associated with noxious stimuli
Autonomic activation that accompany exposure to a noxious stimulus (fight or flight)

Question 21

What are the two systems which discriminate between the first and second pain?

Answer 21

The anterolateral system (spinothalamic system) supplied information to different structures in the brainstem and forebrain

Sensory-discriminative pain (first pain) = spinothalamic tract - VPL nucleus of thalamus - somatosensory cortex

Affective-motivational (second-pain) = mediated by complex pathways that reach integrative centres in the limbic forebrain

Question 22

What are the targeted structures of the affective-motivational pain projections?

Answer 22

Reticular formation
Periaqueductal grey
Deep layers of the superior colliculus
Parabrachial nucleus in the rostral pons
Thalamus
Hypothalamus
Amygdala
==
Anterior cingulate cortex and insular cortex

Question 23

What is hyperalgesia?

Answer 23

Following a painful stimulus associated with tissue damage, stimuli in the area of the injury and surrounding region that would ordinarily be perceived as slightly painful, are perceived as significantly more so

E.g., increased sensitivity to temperature that occurs after sunburn

Question 24

What is peripheral sensitisation?

Answer 24

Results from the interaction of nociceptors with inflammatory substances released when tissue is damaged

These substances arise from activated nociceptors or from non-neuronal cells that reside within or migrate to the injured area

Question 25

Explain how peripheral sensitisation works?

Answer 25

Nociceptors release peptides and neurotransmitters such as substance P, calcitonin gene-related peptide (CGRP) and ATP all of which further contribute to the inflammatory response

Non-neuronal cells that contribute include mast cells, platelets, macrophages, endothelial cells, neutrophils etc - these cells are responsible for releasing extracellular protons, arachidonic acid and other lipid metabolites, histamines etc

Most of these substances interact directly with receptors or ion channels of nociceptive fibres augmenting their response

Question 26

How does the analgesic or placebo effect work?

Answer 26

Activation (electrical stimulation) of descending pain-modulating pathways that project to the dorsal horn of the spinal cord as well as the spinal trigeminal nucleus and regulate the transmission of information to high centres creates an analgesic effect

Periaqueductal grey matter of the midbrain is a major region that produces this effect - electrical stimulation at this site inhibits the activity of nociceptive projection neurons in the dorsal horn of the spinal cord

The analgesic effects of stimulating the periaqueductal grey are mediated through various brainstem sites e.g., reticular formation, nucleus raphe magnus, parabrachial nucleus

Question 27

What are the descending systems that modulate the transmission of ascending pain signals?

Answer 27

Neurotransmitters such as noradrenaline, serotonin, dopamine, histamines, acetylcholine can exert both facilitatory and inhibitory effects on the activity of neurons in the dorsal horn

Descending projections can exert their inhibitory effects on a variety of sites within the dorsal horn including the synaptic terminals of nociceptive afferents, interneurons and synaptic terminals of other descending pathways