Pain

Question 1

what do inflammatory mediators do? give some example ones.

Answer 1

they can activate free nerve endings.
Any four from, Bradykinin, prostaglandin, histamine, hydrogen ions, potassium ions, nerve growth factor and serotonin or substance P.

Question 2

DESCRIBE THE PROCESS OF SENSITISATION (20)

Answer 2

First order nociceptive neurons respond to noxious stimuli by releasing a chemical transmitter called glutamate in the dorsal horn of the spinal cord. The glutamate activates second-order sensory neurons which carry the nociceptive (pain) signals via the spinothalamic tract to the brain.

Low-level activation of the first order neuron triggers low level of glutamate release. This glutamate activates AMPA glutamate receptors on the second order neurons. The resulting signal goes up the spine via the spinothalamic tract. These pain signals find their way to various parts of the brain and may be involved in triggering a pain experience.
However, there are two types of glutamate receptors on the second order neuron, AMPA receptors but also NMDA receptors.

If the first order neuron is heavily activated, with a larger noxious stimulus or for a longer period, a larger quantity of glutamate will be released. This still can activate the AMPA receptors but importantly it can also lead to activation of the second type of receptor, the NMDA receptors.

Once the NMDA receptors are activated, it cause sensitisation in the second order neuron. The second order neuron starts to send larger or stronger signals to the brain. This process is one form of central sensitisation. The second order neurons will respond much more strongly under these circumstances. So, any nociceptive signals carried via this pathway will be amplified before they arrive at the brain. This is likely to increase levels of central pain perception.

Question 3

DESCRIBE THE WHOLE PAIN ENCODING PROCESS (20)

Answer 3

Nerve endings are activated when tissue is damaged-
When the tissue is damaged, inflammatory mediators are released by the tissue such as mast cells. Mast cells produce histamine and serotonin as part of the inflammatory response. These cause the free nerve endings to send action potential up to the CNS. The free nerve endings are acting as nociceptors, so send nociceptive signals to the brain via the spinal cord. Prostaglandin acts as a sensitiser, so increases the level of activation of the free nerve endings. This makes the tissue more sensitive.

Continued damage to the tissue causes peripheral sensitisation, which is a positive feedback loop that acts as a vicious cycle. Persistent activation of free nerve endings causes them to release substance P, which is a powerful vasodilator that triggers neurogenic inflammation. It also activates mast cells, which degranulates and releases histamine. This increases the activation of free nerve endings, so causes the cycle to complete as more substance P is released, and this all happens again. This increases the pain experience.

Continuous damage to the tissue also causes central sensitisation, which can increase the intensity of the pain experience due to NMDA receptors. In the spine, the first order neuron releases glutamate as its main neurotransmitter across the synapse. It activates cell surface receptors on the second order neuron called AMPA receptors. This lets positive ions into the cell, which triggers the second order neuron to send action potential to the thalamus. However, with continuous damage to the tissue, an increasing amount of glutamate is released and a second set of cell surface receptors on the second order neuron are activated. These are called NMDA receptors, and trigger the second order neuron to be more responsive, so making it more sensitive. This increases the pain experience.

Question 4

what happens when a tissue is damaged

Answer 4

When the tissue is damaged, inflammatory mediators are released by the tissue such as mast cells. Mast cells produce histamine and serotonin as part of the inflammatory response. These cause the free nerve endings to send action potential up to the CNS. The free nerve endings are acting as nociceptors, so send nociceptive signals to the brain via the spinal cord. Prostaglandin acts as a sensitiser, so increases the level of activation of the free nerve endings. This makes the tissue more sensitive.

Question 5

describe peripheral sensitisation

Answer 5

Continued damage to the tissue causes peripheral sensitisation, which is a positive feedback loop that acts as a vicious cycle. Persistent activation of free nerve endings causes them to release substance P, which is a powerful vasodilator that triggers neurogenic inflammation. It also activates mast cells, which degranulates and releases histamine. This increases the activation of free nerve endings, so causes the cycle to complete as more substance P is released, and this all happens again. This increases the pain experience.

Question 6

describe central sensitisation

Answer 6

Continuous damage to the tissue also causes central sensitisation, which can increase the intensity of the pain experience due to NMDA receptors. In the spine, the first order neuron releases glutamate as its main neurotransmitter across the synapse. It activates cell surface receptors on the second order neuron called AMPA receptors. This lets positive ions into the cell, which triggers the second order neuron to send action potential to the thalamus. However, with continuous damage to the tissue, an increasing amount of glutamate is released and a second set of cell surface receptors on the second order neuron are activated. These are called NMDA receptors, and trigger the second order neuron to be more responsive, so making it more sensitive. This increases the pain experience.

Question 7

describe what the pain gate theory is

Answer 7

Rubbing the area of the skin that has been damaged reduces the amount of pain felt in that region. There are another set of neurons on our skin. A-beta fibres carry any sense of touch from these neurons to the spine, which then activate a set of interneurons called enkephalins. This is an inhibitory transmitter, so it inhibits nociceptive signals from getting to the brain. Therefore, pain is reduced in that area.

Question 8

define pain

Answer 8

An unpleasant sensory and emotional experience associated with actual or potential tissue damage. It is a personal experience that means different things to different people, due to varying degrees of biological, psychological, and social factors. So, the same pain experience can be experienced at different intensities to different people.

Question 9

define the process of nociception

Answer 9

Nociception is the neural process of encoding noxious stimuli. A series of neurons carry action potential from the receptor to the brain. It is different to pain- it is just a series of electrical signals.

Question 10

what is a nociceptor

Answer 10

a nerve ending that senses damage to the skin. It is a first order neuron that carries action potential to the spine. It is a receptor that responds to inflammatory mediators or damage to the tissue. There are 2 types of nociceptive cell (fibre)- A-delta and C fibres

Question 11

define what is meant by sensitisation. describe the 2 types

Answer 11

– this is the increased reactivity of neurons. There is central sensitisation in the spine and peripheral sensitisation in the tissues. With central sensitisation, NMDA receptors are triggered with strong and repeated activation, which causes the second order neuron to become sensitised. With peripheral sensitisation, there is a positive feedback loop that causes substance P to be increasingly activated, leading to the first order neuron to become sensitised.

Question 12

what is hyperalgesia? what are the 2 types?

Answer 12

a state of increased sensitivity following a tissue injury. Primary hyperalgesia where there is a pain local to the site of damage, making only that area of tissue sensitive. Secondary hyperalgesia is where the sensitivity due to tissue damage extends to undamaged areas surrounding it.

Question 13

what is allodynia?

Answer 13

= increased sensitivity to non-noxious stimuli. It is caused by glial cells. They sit on the spine and become activated during the inflammation response. They switch inhibitory input to excitory output, so they are able to trigger a nociceptive situation.

Question 14

what is a herniated disk?

Answer 14

– where the spinal root has pressure on it by part of the spinal disk. This results in neuropathic pain.

Question 15

describe somatic superficial pain as an origin

Answer 15

it’s a sharp fast pain that is localised to a specific area on the skin.

Question 16

describe somatic deep pain as an origin

Answer 16

it’s a slow ache or burn type pain that often diffuses. It comes from muscles, joints, and the deeper skin.

Question 17

describe visceral pain as an origin

Answer 17

= it’s a slow ache or burn type pain that often diffuses. It comes from the organs in the autonomic system and can cause sweating and nausea.

Question 18

define acute pain

Answer 18

= severe or significant pain that lasts less than 3 months. The damage heals and the pain goes away. It is associated with the fight or flight response and can cause anxiety.

Question 19

define chronic pain

Answer 19

= persistent pain that lasts more than 3 months. It is triggered by an injury, and remains even though the healing process has finished. There are complex lifestyle implications due to this. Implications can include irritability, depression, sleep issues, appetite changes. Chronic pain is complex so multifactorial support is appropriate.

Question 20

what is analgesia?

Answer 20

= loss of sensation of pain that results from an interruption in the nervous system pathway between sense organ and brain

Question 21

what is an analgesic?

Answer 21

a drug that causes pain relief.

Question 22

why do we feel pain?

Answer 22

– its an early warning system that alerts to danger such as actual or potential harm. It causes changes to behaviour in order to avoid danger and harm.

Question 23

what does the SCN9A gene varient cause?

Answer 23

causes the gated sodium ion channel to be non-functional. The channel is on neurons that carry action potential around the body, so if these don’t work then no action potential will arrive at the CNS- causing a person not to feel pain.

Question 24

what are the cardinal signs of inflammation

Answer 24

redness, swelling, heat, pain

Question 25

what is the role of histamine in the pain response

Answer 25

histamine is released by mast cells as part of the inflammatory response. Histamine activates the free nerve endings and cause them to send nociceptive signals to the brain via the spinal cord.

Question 26

what is the role of prostaglandin in the pain response

Answer 26

prostaglandin increases the level of activation of the free nerve endings. So, it increases the sensitivity of the damaged tissue.

Question 27

briefly explain how 2 nociceptive fibres carry pain at different speeds

Answer 27

: A-delta fibres carry nociceptive signals more rapidly because they have a larger diameter axon and are myelinated. Myelination means that they have some electrical insulation that speeds up the passage of action potentials. C fibres have a smaller diameter and are unmyelinated which means they carry signals more slowly.

Question 28

what does the indirect spinothalamic do as a contribution to the pain response?

Answer 28

As part of the indirect spinothalamic system the reticular formation receives nociceptive signals. This increases cardiac output, and so increases sweating and heartrate for example. The limbic system also receives nociceptive signals, and it is responsible for emotional responses to the signals. It is responsible for telling us how emotionally significant the damage is.

Question 29

what is referred pain?

Answer 29

it is pain felt in a part of the body other than the actual source of the nociceptive signals. This is because some parts of the body are close together when a person is an embryo, and move apart as they grow. The neural network is set in the embryo, so even as an adult the pain will be sent to the same area of the NS. This confuses the body as to the origin of the pain. For example, a person might have damage in their gall bladder but feel pain in their shoulder.

Question 30

what is the difference between nociception and pain perception

Answer 30

nociception of a series of action potentials that travel to the spinothalamic tract, whereas pain is our brain telling us how important these signals are. Our brain generates the pain experience, which is the reason for it being subjective.

Question 31

what is the difference between afferent and efferent fibres

Answer 31

afferent fibres travel up the spine. Efferent fibres travel down the spine in the descending inhibitory pathway.

Question 32

what is an enkephalin?

Answer 32

= the type of endorphin released in the desending inhibitory pathway. It blocks the action potential from travelling up the spinothalamic tract, reducing the pain experience.

Question 33

what are the systems that allow us to adapt our response to potentially painful stimuli

Answer 33

– peripheral sensitisation, central sensitisation, descending inhibitory pathways. These help us feel more or less pain depending on the social context of the pain.

Question 34

what is neuropathic pain

Answer 34

• It is caused by damage to the somatosensory system. It can be caused by central damage such as stroke or spinal cord injury, which results in central sensitisation. It can also be caused by peripheral damage such as physical damage to nerves, which can result in peripheral sensitisation. This can become pathological, meaning that it can lead to long lasting pain that can have no therapeutic relief. Examples of neuropathic pain include a herniated disk, hyperalgesia, and allodynia.

Question 35

describe how descending modulatory pathways work

Answer 35

The descending modulatory pathways in the pain system can control the levels of nociception and therefore how badly we feel pain. Neurons in the brain stem send efferent fibres down the spine, which release serotonin and norepinephrine in the spine. This triggers endorphins to be released and reduce the amount of nociceptive signals that can travel up the spinothalamic tract, so reduce the central perception of pain. This reduces the pain experience.

Question 36

DESCIBE THE 3 MAIN ANATOMICAL PATHWAYS (20)

Answer 36

The descending modulatory pathways in the pain system can control the levels of nociception and therefore how badly we feel pain. Neurons in the brain stem send efferent fibres down the spine, which release serotonin and norepinephrine in the spine. This triggers endorphins to be released and reduce the amount of nociceptive signals that can travel up the spinothalamic tract, so reduce the central perception of pain. This reduces the pain experience.

the direct spinothalamic tract carries info on temp, pain, and crude touch. When a nerve ending is activated, the first order neuron is the first nerve cell to pick up this pain. The action potential is passed across a synapse to the second order neuron, which has its cell body in the spine. This second order neuron passes the mid line of the body and sends its axon up the spinal cord to the thalamus. The thalamus acts as an info depot, and the second order neuron sends the info across the synapse to the third order neuron. This then carries action potential to the somatosensory neuron.

However, there is also an indirect spinothalamic tract. Pain info is carried through the thalamus, but instead of going to the somatosensory cortex, it is diverted to other parts of the brain such as the brain stem and limbic system. Pain info is also carried to the imigdella, which helps us understand the significance of a pain – emotionally and in relation to a previous experience of pain in that area.

Question 37

describe the mechanism of the direct spinothalamic tract

Answer 37

the direct spinothalamic tract carries info on temp, pain, and crude touch. When a nerve ending is activated, the first order neuron is the first nerve cell to pick up this pain. The action potential is passed across a synapse to the second order neuron, which has its cell body in the spine. This second order neuron passes the mid line of the body and sends its axon up the spinal cord to the thalamus. The thalamus acts as an info depot, and the second order neuron sends the info across the synapse to the third order neuron. This then carries action potential to the somatosensory neuron.

Question 38

describe the mechanism of the indirect spinothalamic tract

Answer 38

However, there is also an indirect spinothalamic tract. Pain info is carried through the thalamus, but instead of going to the somatosensory cortex, it is diverted to other parts of the brain such as the brain stem and limbic system. Pain info is also carried to the imigdella, which helps us understand the significance of a pain – emotionally and in relation to a previous experience of pain in that area.

Question 39

what are the 2 sides of pain?

Answer 39

mechanical and nociception.

mechanical is the nerve connection thru the body.

nociception is the encoding of potentially or acctually threatening stimuli associated with the damage to the body

Question 40

give me 3 types of receptors

Answer 40

1. free nerve endings
2. tactile disks -
3. hair receptors

Question 41

describe the NS - role, mechanism, types of NS

Answer 41

to monitor the internal and external environment, process the info, and direct body and behaviour processes. sensory input tells the CNS what it senses from the external environment, and the body decides what motor action will take place in response.

1. somatic NS is under our concious control so it is connected to skeletal muscle
2. autonomic NS is under our unconcious control, and is the body’s way of maintaining homeostasis. the effectors are smooth and cardiac muscle, glands, and adipose tissue

Question 42

the brain - structure in relation to pain

Answer 42

FPOT

grey matter = made up of brain cells, blood vessels ect.

white matter = axon connections. fibre tracts connect areas of the brain and some connect the brain to the body. an MRI can track these tracts.

somatotopy = a way of organisation where the cortex are organised in a way you can map the areas of the body on the brain surface. this is how we are able to recognise what part of the body is hurt.

Question 43

Inflammatory mediators that activate free nerve endings

Answer 43

Histamine, serotonin, K+, H+