Lecture 14: PAIN

Question 1

Describe pain receptors

Answer 1

bare nerve endings with multiple branches to span a broad receptive field within the skin

Question 2

Where are pain receptors found?

Answer 2

everywhere except the brain

Question 3

Different endings of pain receptors respond to strong ________ stimuli, and/or high ______ and ________ (that are released in damaged tissue)

Answer 3

mechanical
temperature
chemicals

Question 4

Are pain receptors myelinated?

Answer 4

some are and some are not

Question 5

Why is pain useful?

Answer 5

because it can be used to avoid injury, alert us to local injury or aid recovery

Question 6

Pain is carried by two types of nerve fibres. What are these called?

Answer 6

C and Aδ fibres

Question 7

Describe C pain fibres

Answer 7

they have the smallest diameter and are un-myelinated
they have a slow conduction velocity and signal ongoing damage (or potential damage)
they are the “oooooh” of pain rather than the ouch

Question 8

Describe Aδ fibres

Answer 8

they have small diameters and are myelinated axons
they have a faster conduction velocity and signal acute onset of a painful stimulus
they are the ouch of pain rather than the “oooooh”

Question 9

Pain pathways become more sensitive following what? Why is this?

Answer 9

injury or inflammatory disease because the injury site and the area around the injury becomes tender

Question 10

What is the name for pain pathways becoming more sensitive?

Answer 10

hyperalgesia

Question 11

What causes pain pathways to become more sensitive?

Answer 11

changes in CNS synapses and sensitisation of sensory endings by locally released factors

Question 12

Describe what local factors that increase sensitivity of nerve endings are

Answer 12

these are released in the tissue at the site of an injury that can modify a sensation of pain to give us tenderness and increase in sensitivity to any other kind of input

Question 13

What are 5 examples of the local factors that increase sensitivity of the nerve endings?

Answer 13

• K+
• bradykinin
• histamine
• 5-HT
• prostaglandins

Question 14

Describe how K+ has an effect on increasing sensitivity of the nerve endings

Answer 14

There is a high concentration of K+ in the cells and if these cells become damaged and break, the intracellular contents come out, K+ concentration rises, axons locally get closer to threshold and the equilibrium potential of K+ changes so the likelihood of action potentials being generated is increased.

Question 15

What is the role of prostaglandins?

Answer 15

they participate in clotting by being involved in platelet aggregation
and they activate pain fibres

Question 16

Apart from releasing local factors, what is another way to increase the sensitivity of pain fibres?

Answer 16

by increasing the efficiency of the synapse of the anterolateral pathway taking information into the CNS to the brain to be stretched

Question 17

Substance P (CGRP) is released from pain fibres to activate other cells. Give an example of one of the other cells that is activated and describe what this does

Answer 17

a mast cell could be the cell that is activated

a mast cell is granulated with histamine which gives positive feedback to nerve terminals

Question 18

Describe the role of histamine

Answer 18

is gives positive feedback to nerve terminals which recruits neighbouring axons to bring them close to threshold
it is also responsible for itch

Question 19

What is the role of aspirin?

Answer 19

to inhibit the prostaglandins and act as an anti-clotting agent

Question 20

How can we inhibit pain pathways?

Answer 20

gating of pain impulses by non-painful stimulus of nearby nerves (eg rubbing the area) because inputs from nearby non-pain nerves inhibits the response of ascending pain fibres

Question 21

Why does rubbing help stop pain?

Answer 21

because inputs from nearby non-pain nerves inhibits the response of ascending pain fibres because there can only be so much traffic in the pathway travelling up the CNS
if you give this pathway more input from mechanical receptors or cutaneous receptors that the pain gets crowded out and doesn’t reach the brain

Question 22

The pain information gets to the brain via which pathway?

Answer 22

the anterolateral pathway

Question 23

Describe the anterolateral pathway

Answer 23

The first synapse is low in the spinal cord. The point of entry is the dorsal root and it crosses over to the front and goes to the opposite side of the spinal cord and goes up to the brain. The receptors in the brain (somatosensory cortex) are not as accurate at mapping pain as they are at mapping touch receptors

Question 24

Describe the gate control model of pain

Answer 24

Both A and C fibres carrying pain signals enter the dorsal root but so does mechanoreceptors which raise the threshold and close the gate. In the spinal cord, there are inhibitory signals from the brain and there is an interaction between stimulating and inhibiting signals. The pain intensity depends on the modulation gate

Question 25

What are the two major systems of descending control? These describe the pathways to the spinal cord from the brain and brainstem to regulate pain transmission

Answer 25

• endogenous opiates

- endocannabinoids

Question 26

Describe endogenous opiates

Answer 26

They are released at synapses on pain-pathway neurons and activate the natural analgesia system. They are the site of action of centrally acting painkillers such as morphine and codeine. They have an acute effect (they block pathways) and do so immediately

Question 27

Describe endocannabinoids

Answer 27

They are synthesised and released by neurons but are not stored in vesicles. These decrease long term sensitivity to pain and act on pain receptors as well as centrally. Arousal (activation) tunes out pain fibres entirely from consciousness, placebos are effective as well as suggestion and association

Question 28

What do cortical inputs influence?

Answer 28

Cortical inputs (ie. inputs from the cortex) influence and exert control over passages of pain information through the spinal cord at multiple levels through multiple neurotransmitters

Question 29

Peripheral neural pathways, descending pathways from several brain regions and various chemical transmitters (in addition to opiates and cannabinoids) can do what?

Answer 29

modulate pain and inhibit or facilitate perception and modify responses to pain

Question 30

What can modulate pain and inhibit or facilitate perception and modify responses to pain?

Answer 30

Peripheral neural pathways, descending pathways from several brain regions and various chemical transmitters (in addition to opiates and cannabinoids)

Question 31

Diabetic neuropathy can cause tingling or burning at the peripheries. Why is this?

Answer 31

AP sequences or patterns of information that can’t be interpreted in a way that is meaningful or not in a recognisable pattern by a cutaneous receptor. The APs are not at the right frequency

Question 32

Diabetic neuropathy can cause loss of sensation. Why is this?

Answer 32

Because the APs in particular nerves are not being conducted at all. This starts in the periphery where the nerve endings are furthest away from their cell body which resides in the spinal cord

Question 33

What causes hypersensitivity?

Answer 33

the fibres are more likely to fire as the cells metabolism is is starting to be disordered to the extent that they may try and express additional ion channels on the surface to increase sensitivity

Question 34

Pain is often poorly _______

Answer 34

localised

Question 35

Give an example of pain being poorly localised

Answer 35

you could feel pain in your mouth and this could come from cracked teeth or gum disease but it also could be referred pain and actually come from a sinus or ear infection or a migraine

Question 36

What is referred pain?

Answer 36

When feelings/pain from the viscera are referred to the body surface.

Question 37

What causes referred pain?

Answer 37

because sensory neurons from the skin and viscera can travel through the same pathway up to the brain

Question 38

What is neurogenic pain?

Answer 38

Pain felt in one area when it actually occurs in another

Question 39

Give an example of neurogenic pain

Answer 39

Nerve compression can cause pain to be felt in the region of nerve termination. For example if a disc in the spine slips and compresses the sciatic nerve, its membrane becomes distorted so it becomes stretched and is therefore more permeable to ions. This means it is easier to bring to threshold and generate APs. These are interpreted in the brain as coming from the region of the body that that nerve normally innervated (ie, the leg)

Question 40

What is phantom limb pain?

Answer 40

pain being felt in a region that no longer exists

Question 41

What are the two causes for phantom limb pain?

Answer 41

• ongoing activity in nerves that used to come from that part
• invasion of cortical representation for that part by intact body regions.

Question 42

One of the two causes of phantom limb pain is ongoing activity in neurons that used to come from that part. Explain this

Answer 42

the cut endings have no way to regenerate, to elaborate extra Na+ channels to increase the excitability of blunt end of the axons and they can go wrong and become hyper-excitable and fire spontaneously
ie. the nerve is not silent despite having no ending

Question 43

One of the two causes of phantom limb pain is invasion of cortical representation for that part by intact body regions. Explain this

Answer 43

If neurons in the brain are not doing much then they can do other things instead. There is not a lot of sensory input from the face and so the cortex representation of the amputated leg may become activated by inputs from the face but it is still signposted as coming from the leg so you feel stuff from the leg that is not there