Lecture 44: Pain physiology

Question 1

What is the difference between pain and nociception

Answer 1

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage.

Nociception is the sensory process of detecting tissue damage in somatic and visceral structures : (drop in pH, heat >42, mechanical forces)

1.Transduction, 2.Transmission, 3.Perception, 4.Modulation,

Question 2

What are the 4 components of pain

Answer 2

1. Sensory: sharp, achy, heavy
2. Affective: Mood, emotion
3. Autonomic : mainly sympathetic
4. Motor: withdrawal from the pain source, immobilisation, vocalisation

Question 3

What are the physiological responses to pain

Answer 3

Mainly sympathetic effects: Increased HR, BP, RR and Blood sugar.

Decreased gastric motility, blood flow to viscera.

Pallor, dilated pupils. diaphoresis (excessive sweating), nausea

Question 4

What is the pain threshold

Answer 4

The point at which a stimulus is perceived as pain

Question 5

What is pain tolerance and the factors that affect it

Answer 5

• Duration or intensity of pain that an individual will tolerate before initiation of overt pain response.
• Decreased tolerance: repeated exposure to pain, fatigue, boredom, apprehension, sleep deprivation

-Increased tolerance:
alcohol consumption, medication, hypnosis, warmth, distracting, strong beliefs/faith

Question 6

How does pain threshold change with age and why

Answer 6

Newborns: less sensitive to pain- or can’t say so

Children (5-18): lower pain threshold than adults

Adults: pain threshold increases with aging as skin becomes more thick so will not be sensitive to pain + peripheral neuropathies

Question 7

Define hyperalgesia, allodynia, causalgia

Answer 7

Hyperalgesia: An increased response to stimulus that is normally painful (heightening pain) whereas
Allodynia: pain due to stimulus that is not normally painful.

Causalgia: a syndrome of sustained burning pain + allodynia after a traumatic nerve lesion

Question 8

Define anaesthesia vs analgesia, Paraesthesia vs central pain

Answer 8

Anaesthesia: absence of all sensory modalities whereas Analgesia: absence of pain in response to stimulation that would usually be painful.

Paresthesia: Abnormal sensation of burning, itching, numbness, tingling usually caused by nerve compression or damage

Central pain is pain associated with lesion of the CNS

Question 9

What is a noxious stimulus

Answer 9

Stimulus that can is potentially or actually damaging to tissue (drop in pH, heat >42, mechanical forces)

Question 10

Compare the two fibres that transmit pain and their two nociceptor types- what characteristic of pain, speed

Answer 10

Receptors:
A delta: First pain: fast- sharp, localised, sting:
- Respond to noxious Mechano-thermal stimuli over a certain intensity

C fibres: 2nd pain: slow- dull, diffuse ache:
-Respond to more than one type of noxious stimuli: Mechanical, Thermal, Chemical

Fibres:
A delta: fast- myelinated, medium diameter,
C fibres: slow-unmyelinated, small diameter

Question 11

Describe what happens at the Transduction step and where

Answer 11

At Level of tissues

1. Noxious stimuli cause release of chemicals- SubP, PG, 5HT, ACh
2. Activating nociceptors
3. Leading to AP

Question 12

Describe what happens at the Transmission step and where

Nociceptor excitation is conducted via a combo of Electrical AP and chemical neurotransmitters at the synapses.

Answer 12

1. 1st order neuron enters SC through Dorsal root where it synapses with 2nd order neuron in Dorsal horn
2. 2nd order neuron decussates through ventral white commisure, travels up through brainstem and then synapses with thalamus
3. 3rd order neuron goes to then to sensory cortex

Question 13

What are the two main classes of dorsal horn cells that the 1st order neuron synapses with, which lamina, stimuli and the fibres that innervate them

Answer 13

1. Nociceptive specific cells: in rexed lamina 1 and 2 activated only by noxious- high intensity stimulation
   (a- delta or c fibres)
2. Wide dynamic range: rexed lamina 5. Activated by both noxious and innocuous cutaneous or visceral stimuli (eg. touch)
   (A delta, C and A beta fibres)

Question 14

What are 3 examples of excitatory neurotransmitters and 3 inhibitory

Answer 14

Excitatory:

• ACh,
• monoamines (NE, dopamine, Histamine),
• neuropeptides (sub P)

Inhibitory:

• GABA in brain
• Glycine in spinal cord
• Endogenous opioids (enkephalin, endorphin, dysnorphin)

Question 15

What is the pathway of pain transmission from the head and face to sensory cortex

Answer 15

1. 1st order neuron: TG sensory nerves-> trigeminal ganglion
2. 2nd order Go to Trigeminal spinal nuc. in the Brainstem ( lower pons+ medulla)
3. Decussates to join the Trigeminal lemniscus. goes to the Thalamus
4. 3rd order: Thalamus-> cortex

Question 16

What is the Neo-spinothalamic tract and Paleospinothalamic divisions of the spinothalamic tract for pain

Answer 16

1. Neo: for A-delta (lateral). Starts from lam 1 then decussates through ant commissure carrying info through midbrain, thalamus to Post Central Gyrus.
2. Paleo: C fibres (medial)
   relay with interneurons in lam 2&3 then decussates through ant commissure carrying info to Reticular formation in pons/midbrain and to the Limbic system for emotion

Question 17

Where is Perception of pain processed and what response/sensation does it control

Answer 17

Done in
1. Reticular system: autonomic and motor response to pain

2. Limbic system: emotional and behavioural response
3. Somatosensory cortex: perception and interpretation of sensation (localisation)

Question 18

What is Modulation of pain and what are the ways it occurs

Answer 18

Modulation of pain: where there is a difference between the objective reality and subjective response to a painful stimulus

Pain signal

• Dampening: Gate control
  a) segmental inhibition:
  b) descending inhibitory nerve from higher systems
• Amplification
  a) Windup in dorsal horn

Question 19

Explain Gate control theory and how it helps to dampen pain signals-

a non painful stimulus can block the transmission of noxious stimulation

Answer 19

At the segmental level

1. A-delta and C fibres synapse with 2nd order neuron to the cortex at the segmental level
2. However inhibitory interneurons synapse on the 2nd order neuron as well.
3. They produce enkephalin (opioid) which bocks neurotransmitter release from A-delta + C fibres, therefore stopping pain transmission to the brain.
4. The inhibitory interneuron is stimulated by A beta fibres (carrying light touch information)

Question 20

What path does descending inhibitory nerve take to stimulate the inhibitory interneuron in the spinal segment

Answer 20

1. in the Midbrain, periaqueductal grey is stimulated by ascending pain signal
2. This activates neurons to
   a) Locus ceru leus in Pons
   b) Nucleus Raphe magnus in medulla
3. Descending neurons from LC and NRM go to inhibitory interneuron in spinal segment and release Noradrenaline and 5HT respectively
4. Leads to enkephalin production

Question 21

What are the physical, emotional and mental conditions that will open gate to pain or close it

Answer 21

Physical

• O: Injury is super bad.
• C: Medications like opioids can block the gate.

Emotional:

• O: Anxiety, worry tension
• C: Positive emotions, relaxation

Mental :

• O: focusing on pain + boredom-
• C: Intense concentration or distraction. life activities

Question 22

What does Wind up (Pain amplification) mean and what two conditions does it cause

Answer 22

Process of increased AP output from the 2nd order dorsal horn cells in response to sustained low frequency input from nociceptive afferents via C fibres.
(when pain isn’t treated properly)

leading to formation of
2ndary hyperalgesia and allodynia

Question 23

What is the mechanism of Windup

Answer 23

1. Extended source of pain stimulates C fibres, leading to increased glutamate and Substance P release.
2. This stimulates
   receptors on the 2nd order neuron in the dorsal horn (AMPA, NMDA, NK1) which leads to increased calcium influx in the 2nd order neurons
3. This causes pathophysiological changes in 2nd order neurons = lowering of receptors threshold
4. Thus becoming more responsive to all its inputs - even touch stimulus
5. This would cause central sensitization - heightened sensation of pain and 2ndary hyperalgesia and allodynia

Question 24

What algesic substances are released from damaged cells, platelets, plasma, mast cells, and 1’ nerve afferents that triggers nociceptors

Answer 24

Damaged cells: leukotriene, PGs, K

Platelet: 5HT
Plasma: bradykinin

Mast cells: histamine

1’nerve afferents: Substance P

Question 25

What are the 3 types of Neuropathic pain and what is it sensitive to (not opioids)

Answer 25

1. Peripheral neuropathic pain- nerves damaged themselves eg. trigeminal neuralgia: a-delta type pain or pins and needles
2. Central:
   Thalamic pain syndrome after stroke in thalamic sensory relay or damage of the spinal cord
3. Complex regional pain syndrome/aka reflex sympathetic dystrophy/causalgia

Treatments: membrane stabilisers, tricyclics, spinal cord stimulator.

Question 26

What are the causes, symptoms and treatment of Complex regional pain syndrome

Answer 26

Due to major injury/trauma there is severe debilitating pain.
In the affected limb there is abnormal circulation, temperature, sweating, loss of function, atrophy, change in hair and skin.

Management is through physical therapy, symp NS blocks and other medications

Question 27

What are the two types of Inflammation (after tissue damage) and which type of hyperalgesia does it cause

(Inflammatory mediators cause changes in pain receptors - lowering their threshold so more sensitive to touch stimulus )

Answer 27

1. Non-neurogenic: Initial pain: 1’ hyperalgesia due to release of algesic substances from bv and CT
2. Neurogenic: 2nd pain: 2’ hyperalgesia due to the release of neuropeptides (SubP, CGRP, NA) from C fibres which act on Mast cells and BV to release more inflam mediators to cause oedema and vasodilation and enter + feedback loop= windup

Question 28

What is the mechanism of referred pain

Answer 28

Neurons supplying the internal organ enter the spine at the same level as cutaneous sensory nerves so brain interprets it as coming in from the dermatome of the cutaneous nerve.

Question 29

Compare acute vs chronic pain: duration, function, onset

Answer 29

Acute has a biological function - warning of tissue injury with a finite duration - recent onset and remits when underlying pathology is resolved.

However Chronic pain has no biological value and persists beyond usual course of acute injury and can recur at intervals

Question 30

Describe the process of transition from acute to chronic pain starting at inflammation from surgery/injury

Answer 30

1. First there is transient activation of nociceptive fibres
2. However, after sustained stimulation they get sensitization of nociceptors: 1’ or 2’ hyperalgesia
3. If there is untreated extended source of pain, the C terminal molecules stimulate glial cells in the dorsal horn to make Cytokines.
4. These will stimulate the afferent c fibres coming in, starting automatic pain signal generation in DH, making a loop,
   Even if the source of pain isn’t there-

Question 31

What are the 5 behavioural and psychological changes in Chronic pain

Answer 31

Depression, anxiety, unease, unpleasantness, fear, sleeping disorders.

Question 32

How is pain assessed

Answer 32

-Verbal scale,
-Visual analogue scale (line)
-Numerical rating: 1-10.
Mild: less than 4
Moderate: 5-6.
Severe: 7+
-Wong baker faces scale for kids.