Week 2-Acute and Chronic Pain

Question 1

Define Acute Pain

Answer 1

• Adaptive pain (allows us to survive) that lasts not longer than three months
• The initiating event is known
• Pain subsides with successful treatment of the underlying injury

Question 2

What are the types of acute pain?

Answer 2

-Common and less common diseases
-Dental surgery
-Therapeutic and diagnostic procedures
-Labour pain
-Injuries (sport, work).

Question 3

What are the main types of Acute Pain which requires hospital treatment as it
poses a risk of chronic pain?

Answer 3

• Post-operative pain
• Post-traumatic pain (after an accident)
• Burn injury pain

Question 4

What are the 3 phases in acute pain requiring different psychological assistance?

Answer 4

1. Emergency Phase
2. Healing Phase
3. Rehabilitation Phase

Question 5

What’s the Emergency Phase?

Answer 5

From the time of injury to stabilisation of the patient.

– Nociceptive pain originating from damaged tissues (associated with inflammation).

– Anxiety and fear requires reassurance, information.

Question 6

What’s the Healing Phase?

Answer 6

-Weeks or months

– Pain can fluctuate; procedural pain due to wound cleaning or mobilization / physiotherapy

– Danger of post-traumatic stress disorder may require counselling intervention

Question 7

What’s the Rehabilitation Phase?

Answer 7

• Pain is deeper, aching, more regional (i.e., background pain)
• Treatment: might involve acupuncture, hypnosis

Question 8

What’s the Physiological Mechanisms involved in post-operative pain?

Answer 8

Induces pain, and primary and secondary
hyperalgesia, lasting several (2-7) days.

Further mechanisms involved:
* Spinal cord reflexes: Decrease wound healing and sensitised nociceptors.

• Fight/flight response: Decreases blood flow and oxygen to healing areas.
• Stress hormones: Cortisol, adrenaline, insulin – reduce pain initially but impair healing.

1. Chemical factors (i.e., hyperalgesia): nociceptor sensation, increased pain = pain
2. Spinal cord reflexes: muscle contractions/spasms uses oxygen (leads to less blood flow step in 3. too), lactate in the blood, nociceptor sensation, increased pain = pain
3. Stimulation of the sympathetic nervous system (i.e., anxiety): less blood flow and decreased oxygen in injured areas, decreased wound (i.e., less blood to assist in reducing pain)
   healing. Cortisol, adrenaline and insulin are involved in decreasing pain.

Question 9

What are the Psychological factors involved in burn pain?

Answer 9

• Associated with extreme pain that is resistant to opioids, and changes in body image
• Patients are susceptive to depression and PTSD, which themselves can exacerbate the pain

Treatment complications:
1. Personality Factors: Challenging behaviours like manipulation or aggression complicate the treatment process.
2. Substance Abuse: Drug-dependent patients may have lower pain tolerance and problematic responses to opioid treatments.

Question 10

Define Chronic Pain and its prelevance

Answer 10

• Pain lasting longer than three months
• In younger people, prevalence is 10-30% of the population.
• In elderly people prevalence is 50-75% of the population.
• 12% have high-impact chronic pain (interferes with day to day life and is disabling)
• 22% have low-impact chronic pain

Question 11

Give examples of Chronic Pain Syndromes

Answer 11

Nociceptive pain:
-Arthritic pain

Neuropathic pain:
-Painful polyneuropathies
-Post-herpetic neuralgia
-Central neuropathic pain

Neuropathic + Ncoiplastic pain (sometimes nociceptive too):
-Low back pain and failed back surgery syndrome
-Phantom pain
-Complex regional pain syndrome

Nociplastic pain:
-Headaches
-Fibromyalgia
-Irritable bowel syndrome
-Burning mouth syndrome

Question 12

Define Nociceptive pain

Answer 12

Caused by stimulation of nociceptors in tissues (aka peripheral nerves containing a-delta and C fibers which detect noxious inputs).

Question 13

What is Arthritis?

Answer 13

-Pain related to malfunction of the joint.

Most common types of arthritic pain:
* Osteoarthritis
* Rheumatoid arthritis
* Gout

Question 14

What is Osteoarthritis?

Answer 14

• Progressive loss of articular cartilage in the joint (i.e., wear and tear) leading to joint pain and limitation of movement.
• OA present in 50% people (ranging from mild to severe) > 75 years; obesity is a risk factor.
• Pain is aching, mostly during movement (so can usually get a good nights sleep). Stiffness is a frequent sign (so limited movement).
• At later stages may develop neuropathic characteristics: pain is sustained during sleep and rest.

Question 15

What’s Rheumatoid arthritis?

Answer 15

-1% prevalence

• A type of Inflammatory polyarthritis: affecting various joints.
• Caused by an autoimmune attack on synovial tissues within the joints, leading to damage to cartilage, bone, ligaments, tendons (so can be disabling if not detected and treated early).
• Joints are swollen, tender and warm; swan neck deformity (change in in flexion within the joints as a result of the inflammatory process, limiting the range of movement)
• Other symptoms: fatigue, loss of weight, subfebrilia, morning stiffness.
• Females show 3x larger prevalence of RA than men (and affects any age)

Question 16

What are the other types of arthritis?

Answer 16

• Gout READ FOR SAQ
• Juvenile idiopathic arthritis READ FOR SAQ
• Psoriatic arthritis
• Lupus

Question 17

Define Neuropathic pain

Answer 17

Arises as a direct consequence of a lesion or disease affecting the somatosensory system

Question 18

What is Neuropathic pain?

Answer 18

-Pain caused by a lesion or disease of the somatosensory system.

-7-10% lifetime prevalence

Can be due to damage to one of:
1. the peripheral nerve fibers
2. the dorsal root ganglion
3. spinal cord
4. the ascending projection pathways
such as the spino-thalamic tract
5. the brain

Question 19

What are some physical symptoms of Neuropathic Pain?

Answer 19

-Pain is usually perceived in extremities, is
spontaneous and does not fade at night.

-Patients would often use ornate words to
describe their pain (crawling insects, pins-
and-needles, electric shock-like, stabbing pains etc.,)

Other relevant features relating to lecture 1 mechanisms:
- Hypo/hyperalgesia for heat and/or cold stimuli.
- Secondary hyperalgesia (dynamic-mechanical and
punctuate)
- Temporal summation (wind-up)

Question 20

What are some psychological symptoms which occur due to Neuropathic Pain? (Melzack & Wall, 2013)

Answer 20

-Impaired sleep as the main problem (lack of energy and concentration problems as a result).

-Increased depression

-Anxiety

Question 21

What are the causes and physiology surrounding Neuropathic Pain?

Answer 21

Two major damages to nerves cause
neuropathic pain:
1. Demyelination
2. Axotomy (nerve cutting/injury)

Physiological features lead to spontaneous pain and hyperalgesia (applies to both demyelination and axotomy):
1. Upregulation of Na+ channels leading to increased neuronal excitability + instable membrane potential in the neuron = lots of spontaneous action potentials generated.
2. Receptor sensitisation due to accumulation of neurotransmitters and
inflammatory mediators at the spinal synapse – a type of central sensitisation.

Question 22

What is the aetiologies of Neuropathic pain?

Answer 22

-Toxic-metabolic: Endocrine (e.g., Diabetes)
Chemotherapy (has demyelination but no axotomy) (Polyneuropathies)

-Autoimmune: HIV/AIDS (has demyelination and axotomy but when severe) (Polyneuropathies)

-Infections: Herpes-zoster -> post-herpetic
neuralgia (has demyelination and axotomy but when severe) (Polyneuropathies + Mono-neuropathies)

-Compressive (nerve entrapment; not painful in itself but becomes painful due to demyelination): Trigeminal neuralgia (has demyelination and axotomy but when severe) (Mono-neuropathies)

-Post-traumatic: CRPS type II, Stroke (has demyelination when severe and axotomy) (Mono-neuropathies)

Question 23

Anatomy and physiology of neuropathy:
What’s Nerve injury sprouting?

Answer 23

-If a nerve is injured (cut), the proximal end seals off (end-bulb), swells, and within hours starts sending new connections to the distal end = i.e., sprouts.

-If sprouts are able to connect (e.g., under blunt pressure, cooling) with the loose end, the function will be restored, no pain.

-If sprouts are unable to connect, sprouts will end blindly in tissues and together with end-bulbs create a tangled knot = nerve-end neuroma. There can be sprouts trapped by tissues along the course of axon -> microneuroma

Question 24

Anatomy and physiology of neuropathy:
What’s Nerve injury sprouting and ectopia?

Answer 24

-Sprouts are never myelinated, have unstable membrane potentials and therefore, can be excited by a variety of
stimuli; they also may show spontaneous firing patterns = ectopia.

• Increased expression of Na+ channels (due to compression of the nerves/axon) and instability of membranes leads to ectopia.

Question 25

What are some features of End-bulbs? (Melzack and Wall, 2013)

Answer 25

-End-bulb and sprouts in injured afferent axon. The myelin sheath is los
for about 250 (long shaped u)m before the end-bulb.

-The end-bulb shows accumulation of Na+ ion channels.

Question 26

Give a Summary of Neuropathic pain physiology

Answer 26

• Nerve damage disrupts normal communication between nerve ends, leading to loss of sensation (negative signs) and neuropathic pain (positive sign)
• Nerve-end neuromas and micro-neuromas generate ectopic action potentials perceived as pain
• Ectopic hotspots on injured nerves have increased sodium channels, making them highly excitable and prone to spontaneous firing
• Other mechanisms are also at play in the spinal cord: accumulation of neurotransmitters and inflammatory mediators.

Question 27

Define Peripheral polyneuropathy

Answer 27

The loss of a range nerve fibres (mononeuropathy is one type)

Question 28

Peripheral polyneuropathy: What’s Diabetic painful neuropathy?

Answer 28

• Axonal degeneration from advanced
  or untreated diabetes mellitus.
• Due to decreased blood supply and
  accumulation of sugars such as sorbitol, both leading to oxidative stress that damages axons.

Question 29

Peripheral polyneuropathy: What’s Acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndr.)?

Answer 29

• Inflammatory neuropathy caused by Epstein-Barr virus
• Only occurs when there is immune deficiency
• Pain mainly in the legs

Question 30

Peripheral polyneuropathy: What’s some other examples?

Answer 30

• Hereditary neuropathy – Fabry’s disease
• Toxic and nutritional neuropathy – Beriberi
• Human Immunodeficiency Virus (HIV)

Question 31

What’s Post-herpetic pain syndrome?

Answer 31

• Acute or chronic pain occurring after infection by Herpes varicella zoster virus (chickenpox). (Herpes = something creeping (gr.); zoster = belt)
• Varicella virus gains access to the
  sensory nerves in the skin and passes to the dorsal root ganglion cells. It is re-activated when immune mechanisms fail (age, stress, illness).

Question 32

What’s Post-herpetic neuralgia?

Answer 32

• Pain the acute phase:
  – Vesicular eruptions (rash) of the skin
  is associated with inflammation of the deeper skin layers (shingles) and inflammatory damage to nerves
  (neuropathic pain).
• Pain the chronic phase (10-20% of
  cases):
  – Neuropathic pain known as post-
  herpetic neuralgia in the affected
  dermatome.
  – Pain aggravated by touch; clothes
  may cause unbearable pain (dynamic-mechanical hyperalgesia (allodynia)).

Question 33

Post-herpetic neuralgia: What are the Three main pathophysiological subtypes which
are distinctive to PHN?

Answer 33

1. Irritable nociceptors. Mechanism: due to
   abnormally functioning primary afferent neurons that generate and maintain pain (primary hyperalgesia) (a-delta and c fibers)
2. Deafferentation-type pain with allodynia.
   Mechanism: possible spouting of Aβ primary afferents into areas of the dorsal horn that have lost their normal pain fibre input (invasive)
3. Deafferentation-type pain without allodynia. Mechanism: Spinal sensitisation, in which the loss of both large and small diameter sensory afferent fibres leads to spontaneous discharges in the de-afferentiated central neurons (misbehaving and lost: second-order projection neurons)

Question 34

What’s Trigeminal neuralgia – tic douloureux?

Answer 34

Painful disease of older age (usually occurs
at the age 50-70).
Cause: compression of the trigeminal
nerve near the face and jaw (5th cranial nerve), usually by the superior cerebral artery

Symptoms and signs:
* Pain is elicited by a trigger: chewing, touch,
talking, swallowing, therefore patients may
lose weight by avoiding eating.
* Pain is electric shock-like, stabbing and
unilateral, lasting up to 2 min each time.
* Patient’s face can get distorted (“freeze”),
patient may cry.
* Allodynia - patients may stop washing their teeth/face or shaving.

Treatment: largely successful with decompressing the nerve.

Question 35

Central pain – What are the types of lesions in the CNS?

Answer 35

Spinal cord lesions:
* Usually as the result of trauma to the spinal cord (e.g. car accident).
* Often associated with phantom sensations from regions below the level of injury (e.g. walking).

Brain lesions:
* Usually resulting from stroke (lack of oxygen, or bleeding)
* Damage of thalamus, brainstem, subcortical white matter (e.g., spino-thalamic tract) and cortex.

Question 36

Central pain – Give examples

Answer 36

Thalamic syndrome (central post-stroke pain): a lesion in the thalamus (but also in medulla or elsewhere).

Multiple sclerosis (focal demyelination in the CNS): due to inflammation related to an auto-immune reaction. Pain is often the first sign of the start of MS.

Syringomyelia: a cyst (“syrinx”) filled with fluids in the spinal canal compressing nerves and tracts, causes bilateral pain in arms, shoulders, and thorax.

Question 37

What’s Low-back pain?

Answer 37

Pain in the lower back, buttocks and thighs (may shoot into legs). LBP comes in attacks which last weeks, however, it may become chronic.

• 40-60% of adults experience LBP episodes during lifetime (in developed countries).
• 10-20% lifetime prevalence of chronic LBP
• Disability due to chronic low back pain is 2-5% in USA.

Risk factors:
* Heavy manual work, bending, twisting
* Sedentary jobs and being overweight
* Others: Age, cigarette smoking

Question 38

What are the causes to Low-back pain?

Answer 38

Known causes (10-15% of cases):
1. Axial pain (mechanical – nociceptive pain), e.g., muscle strain from trauma or repetitive motion

2. Radicular pain (non-mechanical pain, sciatica – neuropathic pain) caused by compression, inflammation and/or injury to a spinal nerve root (DRG)
3. Referred pain (nociceptive and neuropathic) E.g., to the hips and posterior thighs, in degenerative disc disease between the vertebrate.

Unknown causes (85-90% of cases):
Idiopathic low back pain (also known as primary low back pain) is thought to be nociplastic in origin.

Question 39

What’s Failed-back surgery syndrome?

Answer 39

Chronic pain in the back and/or leg after a
technically successful surgery of the vertebrae, vertebral discs, or spinal cord.
FBSS is a complication of a technically successful surgery.

Causes:
– mechanical damage of the dorsal root(s) – nerve fibres outside the spine
– thickening of the dura mater (a membrane
enveloping the spinal cord), which compresses the dorsal root

Risk factors:
(1) pre-operative, (2) intra-operative and (3) post-operative

Question 40

What’s Phantom limb pain?

Answer 40

• Pain felt in a nonexistent, amputated limb.
• Occurs in up to 80% of amputees.
• Distal parts of the limb (e.g. hand, feet) are more often the sites of phantom-limb pain.
• The amputated limb is felt to be in a twisted or cramped position (patients report their nails being pulled from the nail
  beds).

Other phantom sensations:
(1) kinesthetic, positional
(2) kinetic, motions
(3) exteroceptive (cutaneous sensations)

Question 41

What are some theories on the causes of Phantom limb pain?

Answer 41

Neuropathic elements:
1. Peripheral nerve sensitisation:
– Nerve damage from ischaemia
– Pro-nociceptive factors (cytokines,
prostaglandins, substance P) cause primary
hyperalgsia.

2. Spinal cord plasticity:
   – NMDA receptor-mediated secondary
   hyperalgesia

Nociplastic elements:
3. Brain changes:
– Cortical reorganisation in the somatosensory cortex

Question 42

Does phantom limb pain have cortical reorganisation? (Flor, 2002)

Answer 42

-Found reorganisation in the primary somatosensory and motor cortex in patients who had a unilateral arm amputation with phantom limb pain.

-The participants had to pucker their lips at a a metronome-paced speed while functional magnetic images were taken.

-Only in amputees with phantom limb pain did a shift of the mouth representation into the hand representation occur; those without pain and the healthy control do not display a similar shift.

Question 43

What are some psychological factors in Phantom Limb Pain? (MacIver et al., 2008)

Answer 43

-Emotions, stress, and lack of sleep increase phantom limb pain.

-So, while pharmacological treatments fail to work, there are promising results with
motor imagery and mindfulness meditation.

-Found that after the intervention, when p’s puckered their lips there were fewer brain region activations which was also associated with the decrease in the extent of pain intensity and unpleasantness.

Question 44

What are some distinguishing symptoms of Complex regional pain syndrome (CRPS)?

Answer 44

• Continuing pain that outlasts injury
• Usually, unilateral on one limb, but can spread to other body regions
• Allodynia, hyperalgesia
• Swelling and/or change in skin temperature more than 1.1°C relative to homologous part of the body
• Altered patterns of hair, skin, or nail growth
• Altered body perception and proprioception

Question 45

Classifying CRPS: what are the Post-1993 taxonomy (subtypes) and symptoms/signs?

Answer 45

CRPS Type I (previously, reflex sympathetic dystrophy):
* A clear initiating noxious event (wound,
fracture, inflammation)
* No obvious nerve damage, but still
neuropathic-like symptoms (e.g. allodynia)
suggesting nerve hypersensitivity.

CRPS Type II (previously, causalgia):
* Clear presence of injury of a major nerve trunk
* Symptoms otherwise the same as Type 1

Question 46

Classifying CRPS –What are the Warm vs. Cold subtypes?

Answer 46

1. Warm CRPS:
   * More common in the acute phase of CRPS
   * Characteristics: warm, red, and swollen extremity.
   * Mechanisms: Inflammation causing vasodilation and increased skin temperature.
2. Cold CRPS:
   * More common in the chronic stage of CRPS
   * Characteristics: Presents with a cold, dusky, sweaty extremity.
   * Mechanisms: Sympathetic hyperactivity - circulating adrenaline may cause vasoconstriction and nerve sensitisation. Possibly, cortical reorganisation.

Question 47

What’s Nociplastic pain?

Answer 47

Pain that:
(1) arises from altered nociception despite no clear evidence of actual or threatened tissue damage
(2) no evidence for disease or lesion of the
somatosensory system

Question 48

What are contributing factors to Nociplastic / Centralised Pain?

Answer 48

1. Psychosocial and Cognitive Factors: Stress, anxiety, depression, and negative pain beliefs
2. Chronic stress and Hypothalamic-Pituitary-Adrenal (HPA) dysregulation
3. Genetic Factors

Question 49

What are Core mechanisms to Nociplastic / Centralised Pain?

Answer 49

1. Increased excitability/sensitivity of neurons in the CNS, due to excitatory neurotransmission (glutamate), decreased inhibition (e.g. GABA), expansion of receptive fields, and neurogenic inflammation (e.g. substance P, cytokines).
2. Dysfunction of descending pain modulation: Impaired pain inhibition
   and enhanced pain facilitation from the brain to the spinal cord..
3. Cortical reorganisation / anormal brain connectivity: Re-wiring of brain networks that disrupts normal sensory processing and pain regulation.

Question 50

What are the common types of headaches and its provoking factors?

Answer 50

1. Migraines: a) without aura, b) with aura
2. Cluster headache
3. Tension-type headache

Provoking factors:
* Stress, poor sleep
* Hormones: Abrupt fall of estrogen level (pre-menstruation, menopause)
* ? Chocolate, alcohol (sparse data on this)

Question 51

What’s a migraine?

Answer 51

Hemikranios (gr.) – hemicranium (lat.) –megrim (old English) (half of the head)

• 1 year prevalence: 12% in developed countries
• One third of patients are severely disabled during migraine attacks

Characteristics:
* Attacks lasting 4-72 hours.
* Pain is pulsatile (throbbing) and usually
unilateral, associated with nausea/vomiting,
photophobia (sensitivity to light) and phonophobia (sensitivity to noise).
* Occurs with or without aura (prodrome).

Risk factors:
* Aggravated by physical exercise (causing changes in blood flow).
* More frequent in women compared to men (3:1)
*Age: 40-45 in females, 25-55 in males

Question 52

Migraine –What are forms of aura and causes?

Answer 52

Forms of aura:
* Visual disturbances, images of stars or sparks or zig-zag lines (suggests that the occipital cortex is at the beginning of the attack)
* Unpleasant smell, confusing thoughts.
* Aura lasts about about 20 min and transforms into pain or a temporary normal period.

Pain and aura causes:
* Vasospasms producing ischemia
* The ensuing acidosis leads to vasodilation
and pain
* Pulsatile quality of pain supports the view of vascular involvement
* Neurological origin: Brainstem (controls
vasomotor tone) activated prior to migraine
onset - central nociplastic mechanisms.

Question 53

What are symptoms of a Cluster headache?

Answer 53

Symptoms:
* Strictly unilateral (however, the sides can swap), rapid onset and offset.
* Pain lasts for 45-90 min (“bout” of cluster headache); occurs from 1 to 8 per day (migraines last longer)
* Recurrent with a striking rhythmicity (circadian, circannual i.e., times of the day/year where people are susceptible to cluster headaches)
* Not aggravated by physical activity, no nausea (unlike Migraines)
* Associated with lacrimation, ptosis, restlessness, agitation

Epidemiology:
* 3-7 times more frequent in females than in males
* Chronic cluster headache in about 10% of patients

Question 54

What are symptoms of Tension-type headaches (TTH)? (Holroyd et al., 1999)

Answer 54

Symptoms:
* bilateral head pain, non-pulsatile (unlike migraines), tightening
* mild to severe intensity, can be disabling for the duration of attack
* not aggravated by physical activity, no nausea (like cluster headaches)
* head muscle tone increased, myofascial tenderness

Epidemiology:
* >60% life prevalence, becomes chronic in 3% of population
* Most common in ages 30-39 years
* Educational level is positively associated with TTH
* No obvious gender preponderance

Question 55

What is Fibromyalgia?

Answer 55

• Syndrome of unknown aetiology
• Upper and lower body symmetrical musculo-skeletal pain.
• Pain is in soft tissues around joints capsules and periosteum (tendons, bursae, muscles)
• Prevalence in general population 1-4%,
  4×females.

Symptoms:
1. Persistent, widespread pain (aching, throbbing, stabbing) in soft tissues.
2. Widespread allodynia.

Tender points: 18 points on the body are tested using a standardised pressure of 4kg/1cm2 (is painful for those suffering with FMS)
- having tenderness in 11 out of 18 points supports the diagnosis of FMS.

Question 56

What are further symptoms of Fibromyalgia?

Answer 56

• Morning stiffness – lasts 45 min – 4 hours, and associated with pain.
• Irritable bowel syndrome.
• “Fibro fog”: fatigue, headaches, dizziness, double vision, cognitive impairment (e.g. memory loss), insomnia.
• Depression
• Hypervigilance to pain: vigilance to somatosensory (non-painful) stimuli is higher in FMS than in controls: patients scan their bodies for somatic sensations.

Possible mechanisms:
* Centralised pain
* Neuropathic contributors: neuropathy of small fibres; possible autoimmune mechanisms (involving DRG glial cells)

Question 57

What is Irritable bowel syndrome?

Answer 57

• Unpleasant, painful sensations in the abdomen
• Associated with frequent stool, abnormal stool form, and/or abnormal stool passage.

Risk factors:
* More prevalent in females than males (2-2.5 : 1)
* Usually occurs at the age of 30-50 years.
* Frequently associated with fibromyalgia
* Associated with psychiatric syndromes (somatisation, hypochondriasis).

Possible mechanisms:
* Centralised pain
* Peripheral contributors: increased gut motility, mucosal inflammation, autoimmune mechanisms affecting the gut, changes in gut microbiome

Question 58

Give other examples

Answer 58

Burning Mouth Syndrome (BMS):
* Oral pain, disturbances of taste.
* No evidence of a peripheral tissue origin, nor nerve damage.
* Centralised pain is suggested by association of pain with psychological factors and stress.

Temporo-mandibular disorder (TMD):
* Pain in the temporomandibular joint and
masticatory muscles.
* May be initiated by physical trauma.
* Centralised pain is suggested by (1) a poor
correlation between pain severity and
joint/muscle pathology and (2) high impact of psychosocial factors and stress.

Question 59

Final Thoughts Summary