Psychobiology Of Pain (Year 3)

Question 1

Give pain pathways

Answer 1

Spinal cord processing, spinothalamic tract

Question 2

Give some mechanisms of pain

Answer 2

Gate control theory
Sensitisation
Temporal summation
Referred pain

Question 3

Give a definition of pain

Answer 3

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage

Question 4

Give the three dimensions of pain

Answer 4

Dimensions of pain:
sensory-discriminative: physical stimuli and their processing
affective: unpleasantness, emotions
cognitive-evaluative: situation, context, memory, cognition

Question 5

give and explain the three basic types of pain

Answer 5

Nociceptive = caused by stimulation of nociceptors in tissues (Lecture 1) (noceo, nocere = causing harm, Lat.)

Neuropathic = arises as a direct consequence of a lesion or diseases affecting somatosensory system (IASP) (Lecture 2).

Nociplastic = Pain that (1) arises from altered nociception despite (2) no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or (3) evidence for disease or lesion of the somatosensory system causing the pain. (IASP, 2017) (Lecture 2).

Question 6

Give some of the body regions which lack nociceptors

Answer 6

brain tissue (however, the meninges do have nociceptors

bone (however, the periosteal membrane has nociceptors)

interstitial tissue of the kidney (however, the capsula has nociceptors)

liver (however, the liver capsula has nociceptors)

lungs (however, pleura has nociceptors)

Question 7

Describe the basic scheme of pain

Answer 7

Free nerve endings in tissues
🡣
Peripheral nerve
🡣
Dorsal horns of the spinal cord
🡣
Spinal cord pathways
🡣
Brain centres

Question 8

Describe the structure and function of pain sensors

Answer 8

The cell of axons of peripheral nerve fibres are in the dorsal root ganglia located about 1 cm away from the spinal cord.

Question 9

Give the types of TRP channels for nociception and their ligands

Answer 9

TRPA1 - mustard, oil, THC, <17C
TRPM8 - menthol, eucalyptol 8-26C
TRPV1 - capsaicin, andandamide, protons >43C

increased permeability to cations, especially CA2+

TRPV1 is the primary pain receptor

A triplet of TRPs fully explains heat pain in mice

Question 10

Describe the role of peripheral nerve fibres

Answer 10

• The spinal dorsal root ganglion hosts the cell bodies of neurons in afferent peripheral fibres
• Peripheral nerve fibres transmit information from
  tissues to the spinal cord

Question 11

Describe the roles and structures of A-fibres

Answer 11

A-fibres diameter velocity
a : proprioception 12-20 um 70-120 m/s
b : touch, pressure 5-12 um 30-70 m/s
g : muscle spindles 3- 6 um 15-30 m/s
d : pain, cold 2- 5 um 15-30 m/s

Question 12

Describe the role of B-fibres

Answer 12

B-fibres
preganglionic fibres < 3 um 3-15 m/s
autonomic system

Question 13

Describe the role and structure of C- fibres

Answer 13

pain, warmth,
affective touch < 0.4-1.2 um 0.5-2 m/s

Question 14

Describe and compare the subtypes of A-delta fibres

Answer 14

Sharp, pricking, first pain

Question 15

Describe the structure of the spinal cord

Answer 15

Thin, elongated tubular structure running in the spinal canal, in the openings of individual vertebrae.

Spinal cord comprises bodies of neurons and long axons (connecting with the brain) and short axons (interneurons)

Spinal cord sends a pair of spinal nerves through the openings on sides of vertebrae; these nerves comprise both sensory and motor neurons.

There are 31 pairs of spinal nerves

Question 16

Describe the structure of the spinal cord

Answer 16

Major nociceptive zones
in the grey matter of the
spinal cord:

Lamina I
Lamina II
Lamina V

Lamina I (zona marginalis): primary entry zone for the C and small diameter Ad fibres.
Lamina II (substantia gelatinosa): large number of interneurons capable of post-synaptic inhibition. Entry of Ad fibres and C fibres
Lamina III-IV: the entry zone for the tactile A-b fibres.
Lamina V: large number of WDR cells, converging inputs from visceral nociceptors and cutaneous and muscle afferents, the site of origin of the spinoreticular tract. Inputs into Lamina V stream into both the left and right side of the spinal cord.
Lamina VII-VIII: receive pain information from interneurons rather than directly from afferent fibres; respond to noxious stimuli from either left or right side of the body, and contribute to diffuse pain

Question 17

Describe the structure of the spinal cord neurons

Question 18

Give the laminae responsible for pain

Question 19

Describe the structure and function of lamina 1, 11 and V

Question 20

Describe the role of lamina VII- VIII in nociception

Question 21

Describe and explain temporal summation of pain

Question 22

Define and explain central sensitisation

Question 23

Give a summary of the role of spinal cord processing of pain

Question 24

Describe and explain the role of mediators which sub-serve nociception

Question 25

Describe the structure of the spinothalamic tract

Question 26

Describe how NS cells project to the brain stem

Question 27

Describe the process of gate control theory

Question 28

Define acute pain

Answer 28

• lasts under three months
• adaptive - signals tissue damage and helps protect from further damage
• initiating event is known (injury, infection etc.)
• pain subsides with successful treatment of original injury

Question 29

Give some types of acute pain

Answer 29

• labor pain
• injuries (e.g from sports, work)
• dental surgery

Question 30

Give the main types of acute pain requiring hospital treatment (and pose a risk of chronic pain)

Answer 30

• post-operative pain
• post-traumatic pain
• burn-injury pain

Question 31

Give the three phases in acute pain

Answer 31

1. emergency phase
2. healing phase
3. rehabilitation phase

Question 32

Explain the emergency phase in acute pain

Answer 32

• from the time of injury to stabilisation of the patient
• nociceptive pain originating from damaged tissues
• anxiety and fear are imminent
• psychological intervention: reassure, give information

Question 33

Explain the healing phase in acute pain

Answer 33

• lasts weeks or months
• background pain – fluctuating, sometimes breakthroughs of pain
• procedural pain due to wound cleaning or mobilization/physio
  danger of PTSD
• counselling intervention - patient may need to discuss feelings about body image/loss of body part

Question 34

Explain the rehabilitation phase in acute pain

Answer 34

• deep aching pain
• pain becomes regional
• treatment may include acupuncture, hypnosis etc.

Question 35

Discuss post-operative pain

Answer 35

• induced pain and primary and secondary hyperalgesia lasting 2-7 days
• release of prostaglandins, histamine, bradykinin, substance P + others that sensitize nociceptors

Question 36

Explain some of the mechanisms involved in post-operative pain

Answer 36

• Segmental, spinal cord reflexes leading to muscle contractions/spasms (increased consumption of oxygen). This also increases lactate in the blood.
• Stimulation of the sympathetic nerve system (tachycardia, blood pressure, cardiac work, and a decreased tone of the smooth muscles in gut and urinary system)
• Release of stress hormones: cortisol, adrenaline, insulin. (part of fight or flight - can inhibit pain in the short-term)

Question 37

Describe burn injury pain

Answer 37

• pain is related to tissue damage and therapeutic interventions
• tissue damage - skin burning and direct exposure of nociceptors in severe pain
• burn pain associated with depression and PTSD

Question 38

Describe the therapeutic interventions for burn pain

Answer 38

• wound cleaning, skin stretching, skin transplants, plastic surgery, mobilisation
• pain sustains in spite of intravenous administration of opioids

Question 39

Describe some of the potential psychological factors in burn injury

Answer 39

• pre-injury status is important - 25-75% of patients report depression, substance abuse and suicide attempts prior to injury

implications
- drug-abuse patients may show decreased tolerance to pain - more drug-seeking behaviour and greater tolerance to opioid treatment
- people with personality predispositions may should aggressive behaviour and low frustration threshold
- negative emotions worsen pain (anxiety, depression) - PTSD likely to develop

Question 40

Explain the link between chronic pain and PTSD

Answer 40

• the patient may re-experience the event (thoughts, images, flash-backs etc.)
• ptsd patient avoids situations and conversations associating with event and may have some memory loss for event
• associated with higher physiological arousal - sleep distrubances, hypervigilance, difficulty concentrating

Question 41

Define chronic pain

Answer 41

• pain lasting 3 months or more

Question 42

Give some examples of neuropathic pain conditions and conditions with neuropathic components

Answer 42

• painful polyneuropathies
• low back pain/ failed back surgery syndrome
• CRPS
• phantom pain

Question 43

Give some examples of musculoskeletal pain conditions

Answer 43

• arthritis
• fribtomyalgia

Question 44

Give some examples of nociplastic pain

Answer 44

• irritable bowel syndrome
• burning mouth syndrome

Question 45

Describe and explain neuropathic pain

Answer 45

• pain caused by a lesion or disease of the somatosensory system

Question 46

Give some of the aetiologies of neuropathic pain

Answer 46

• toxic-metabolic (endocrine, chemotherapy)
• post-traumatic (e.g CRPS type ii)
• compressive (nerve entrapment e.g carpal tunnel)
• autoimmune (e.g HIV)
• infections )e.g herpes-zoster ->post herpetic neuralgia

Question 47

Briefly describe how neuropathic pain manifests

Answer 47

• receptor sensitisation due to accumulation of neurotransmitters
• upregulation of Na+ channels leading to increased neuronal excitability and hyperalgesia

Question 48

Explain sprouting in the context of nerve injuries

Answer 48

• 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 = 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 49

Define and explain ectopia

Answer 49

• 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 and instability of membranes leads to ectopia

Question 50

Explain this image of an end-bulb

Answer 50

1. End-bulb and sprouts in injured afferent axon. Myelin sheet is lost about 250 um before the end-bulb.
2. The end-bulb shows accumulation of Na+ ion channels.

Question 51

Describe features of ectopia in nerve injuries

Answer 51

Hot spots on nerve-end neuromas show electrical hyperexcitability
- spontaneous firing in absence of stimuli.
- prolonged firing beyond the duration of stimulation (after-discharges)

C-fibre ectopia: firing at 0.1–10 Hz, increased by cooling, alleviated by warming.
Ad fibre ectopia: firing at 15 - 30 Hz, increased by warming, decreased by cooling.

Question 52

Give some of the factors which contribute to ectopic firing

Answer 52

• chemical agents associated with tissue damage
• inflammation and immune factors (e.g., interleukins)
• noradrenaline released from sympathetic nerve endings
• mechanical stimuli (pressure)

Question 53

Give some of the symptoms in neuropathic pain

Answer 53

1. Presence of spontaneous pain which does not fade away during nights.
2. Decreased or increased thresholds for heat, cold (hypo/hyperalgesia).
3. Dynamic-mechanical and punctuate hyperalgesia
4. Temporal summation: abnormal painful sensations after repetitive non-painful stimulation (wind-up).
5. After-sensations: painful or unpleasant sensation continues beyond the stimulus duration.
6. Paresthesia – abnormal and unusual sensations that are described as neither unpleasant nor painful (tingling).
7. Dysesthesia – abnormal sensations described as disturbing and unpleasant; spontaneous or evoked.
   Other symptoms: hypotonia, sometimes incoordination or apraxia

Question 54

Define peripheral polyneuropathy

Answer 54

As the name suggests, the syndrome belonging to this group would involve damage to peripheral nerves and that a widespread network of nerves will be involved, and is typically caused by disease rather than injury.
- Can affect multiple/ networks of nerves
- Most common is diabetic painful neuropathy

Question 55

Explain diabetic painful neuropathy

Answer 55

• Advanced or untreated diabetes mellitus is associated with symmetric distal polyneuropathy of both small and large nerve fibres.
• Destruction of nerve fibres is attributed to decreased vascular blood supply to the lower extremities and axonal degeneration, and to accumulation of sugars such as sorbitol.
• Pain is deep aching, burning.
• Common in extremities

Question 56

Define acute inflammatory demyelinating polyneuropathy (Guillain-Barre syndrome)

Answer 56

• Inflammatory neuropathy caused by Epstein-Barr virus. The syndrome is also associated with motor weakness sometimes leading to necessity of ventilatory support.
• Removes myelin from nerves
• Pain occurs in 40-75% of patients with G-B syndrome.
• Pain is burning, and occurs in the back and legs. Frequent allodynia.

Question 57

Define Fabry’s disease (Hereditary neuropathy)

Answer 57

• Multi-system disorder affecting peripheral nerves, kidneys and skin.
• It is an X-linked recessive gene disorder manifesting in lack of one lysosomal enzyme (alpha-galactosidase).
• Pain is constant, burning, occurs in hands and feet. Pain can be controlled by antiepileptic and anticonvulsive drugs.

Question 58

Give an example of a toxic and nutritional neuropathy condition

Answer 58

• beriberi
• beriberi is due to B1 (thiamin) hypovitaminosis, which results in disease of nerves and cardiac muscle.
• Symptoms: progressive weakness, paresthesia, dull or lancinating pain usually in distal limbs.
• Treatment with B1 vitamin leads to recovery.

Question 59

Give an example of an immunodeficiency neuropathy condition

Answer 59

• HIV
• HIV is associated with peripheral neuropathy due to vascular deficiency and de-myelination (autoimmune reaction).
• Patients suffer from burning pain and dystesthesia especially in feet.

Question 60

Give some of the main problems for patients with polyneuropathy

Answer 60

• impaired sleep
• increased depression
• anxiety

Question 61

Describe and explain low-back pain

Answer 61

• Pain in the lower back, buttocks and thighs (may shoot into legs).
• LBP comes in attacks which last weeks, however, it may become chronic.
• LBP approaches epidemic numbers: 80% of adult population in USA, and about 40-60% in other developed countries report occurrence of LPB during lifetime. Disability due to low back pain is 2-5% in USA.

Question 62

Give some of the physical factors that contribute to low-back pain

Answer 62

• heavy manual work, bending, twisting
• cigarette smoking
• age
• sedentary jobs and being overweight

Cigarette smoking and LBP: >50% of LBP patients are regular smokers:
direct effects of nicotine on vasculature of the spine?
coughing in smokers may increase the load on the vertebral disk?

Question 63

Describe and explain failed-back surgery syndrom

Answer 63

• Chronic pain in the back and/or leg after a technically successful surgery of the vertebrae, vertebral discs, or spinal cord.
• FBSS has an iatrogenic component because it develops after a technically successful surgery.
• Pain is shooting, burning, frequent allodynia.

Question 64

Describe the etiology of failed-back surgery syndrome

Answer 64

• 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
  - The condition cannot be treated with another surgery
  because the dura mater only gets thicker with each new
  surgery. Therefore, patients with failed back surgery
  syndrome are often treated with a spinal cord stimulator:
  electrical currents to the spinal cord and the medial pain
  system, which opposes the transmission of nociceptive
  impulses.

Question 65

Describe and explain the older taxonomy of complex regional pain syndrome

Answer 65

Older taxonomy: 1. Reflex sympathetic dystrophy
2. Causalgia (caustos = heat)
Reflex sympathetic dystrophy
Focal vasomotor abnormalities
Pain, changes in vasomotor tone and skin colour
Trophic changes (skin, hairs, nails)
No obvious nerve damage

Causalgia: often occurs in war injured people due to damage of peripheral nerves
Burning pain in the territory of the affected nerve
Intermittent temperature changes
Changes in skin colour

1993: Complex Region Pain Syndrome

Question 66

Describe CRPS Type I

Answer 66

• previously reflex sympathetic dystrophy
• presence of initiating noxious event (wound, fracture, inflammation)
• continuing pain, allodynia, hyperalgesia, swelling, changes in blood flow and skin temperature more than 1.1 °C relative to homologous part of the body

Question 67

Describe CRPS type II

Answer 67

• presence of injury of a major nerve trunk
• presence of continuing pain, allodynia or hyperalgesia after nerve injury
• evidence of some time swelling and/or change in skin temperature more than 1.1°C relative to homologous part of the body

Question 68

Describe the pathophysiology of CRPS

Answer 68

• Hypofunction of the sympathetic nerve fibres – this leads to the upregulation of adrenergic receptors in peripheral nerve fibres.
  Effects change over time:
• in acute phase (<6 months), the affected limb is warmer than the non-affected limb due to diminished sympathetic tone
• chronic phase (>6 months) –vasoconstriction, cold, bluish extremity in the chronic period: role of circulating adrenaline, causes sensitisation to nociceptive stimuli

Protective disuse - patient avoid tactile sensations and movements which aggravates pain:
- accumulation of catecholamines in the limb
- lack of natural somatosensory stimulation leading to
vasomotor and central disturbances, decreased functionality of the limb (e.g.,
range of motion)

Question 69

Give the risk factors, prognosis and epidemiology of CRPS

Answer 69

• Not related to age, women have larger prevalence of CRPS than men (3:1).
• Type of injury: trauma, operation, inflammation, infectious disease, some drugs (e.g., anti-tuberculosis drugs). 4-7% of patients with a limb fracture or surgery develop CRPS.
• Risk factor: immobilisation for a long period of time increases the likelihood of CRPS (protective disuse), e.g., rats whose limb has been immobilised for three weeks showed signs of allodynia.
• Prognosis can be good if treatment starts soon after injury and before the pain spreads to the rest of the limb. Patients with CRPS requires an early treatment to have a chance of recovery

Question 70

Define post-herpetic pain syndrome

Answer 70

Chronic neuralgic 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).

In acute phase, vesicular eruptions (rash) of the skin associated with inflammation of the deeper skin layers (shingles). The lesion cures by crusting and often leaves
hypopigmentated areas.

Neuropathic pain is severe, occurs only in the affected dermatome, but normally subsides with treatment.

Question 71

Describe the types of pain involved in postherpetic neuralgia

Answer 71

Types of pain: 1. Background: steady, burning and aching pain
2. Sudden/brief: lancinating, paroxysmal pain

Pain aggravated by touch; clothes may cause unbearable pain (dynamic-mechanical allodynia).

Pain is of variable intensity but 40% of patients report intractable pain.

Chronic pain is associated with depression and reduction of daily activities.

Question 72

Give some of the risk factors of postherpetic neuralgia

Answer 72

Age: almost 75% of people above 70 years are likely to develop chronic pain after HZ infection.
Pain severity in acute phase correlates with the probability of having chronic PHN.
Rash severity: number of vesicles and the size of rash area
Sensory dysfunctions, such as increased tactile/vibration thresholds, in the acute phase, are associated with chronic form.
Greater T-lymphocyte (cell) immunity response in acute phase is associated with chronic form of the syndrome.

Question 73

Describe and explain phantom limb pain

Answer 73

• Pain felt in a nonexistent, amputated limb.
• Pain varies from mild to excruciating, occurs in up to 80% of amputees
• Prognostic factors: strong pre-amputation pain, being female, upper limb.
• Other phantom sensations:
  (1) kinesthetic, positional
  (2) kinetic, motions
  (3) exteroceptive (cutaneous sensations)
• Stump pain is felt in the region of amputation in the existing part of the body (10-25% of amputees)

Question 74

Give the temporal profile of phantom limb pain

Answer 74

• Phantom pain may last decades and then suddenly disappear, and re-appear again spontaneously.
• Phantom pain initially involves the whole limb, later it “telescopes” to the stump.

Quality of pain
- Variable (gnawing, burning, cramping, aching, crushing, shooting).
- Distal parts of the limb are more often the sites of phantom-limb pain.
- The amputated limb is felt to be in a twisted or cramped position during periods of pain (patients report their nails being pulled from the nail beds).

Question 75

Describe the potential treatments for phantom limb pain

Answer 75

Refractory to pharmacological treatment, however, promising results with motor imagery and mindfulness meditation.

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

Question 76

Describe the general mechanisms of heachache

Answer 76

(1) Displacement, distension, inflammation of cranial
vascular structures including carotid and intracranial
arteries.
(2) Sustained skeletal muscle contractions in the neck and head.
(3) Direct pressure on cranial and upper cervical nerves.

Question 77

Give the types of headaches

Answer 77

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

Question 78

Describe and explain migraines

Answer 78

Migraine headaches occur with or without aura (prodrome).

Migraine is an idiopathic chronic pain disorder manifesting in attacks lasting 4-72 hours.

Pain is pulsatile (throbbing) and usually unilateral, associated with
nausea/vomiting, photophobia (light sensitivity) and phonophobia (sound sensitivity). Migraine pain is
aggravated by physical exercise.

Migraine is more frequent in women compared to men (3:1). One third
of patients is severely disabled during migraine attacks.

Question 79

Describe the symptoms and prevalence

Answer 79

Aura and pain: caused by vasospasms producing ischemia; the ensuing acidosis leads to vasodilation and pain – pulsatile quality of pain supports the view of a vascular origin of migraine pain

Forms of aura: visual disturbances, images of stars or sparks or zig-zag lines (suggests that the occicipital 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.

Question 80

Give the prevalence of migraines

Answer 80

Prevalence:
1-year prevalence about 12% in developed countries
the largest occurrence of migraine headaches are between 40-45 in females and 25-55 in males

Question 81

Give research findings on the onset of a migraine

Answer 81

A patient with migraine
headaches without aura
showed increased activation
in the brainstem. The brainstem
can initiate vascular changes
leading to a migraine attack

Question 82

Give the symptoms of a cluster headache

Answer 82

Symptoms:
- strictly unilateral, excruciating, rapid onset and offset
- unilateral, however, the sides can swap
- pain lasts for 45-90 min (“bout” of cluster headache); occurs from 1 to 8 per day
- headaches are recurrent with a striking rhythmicity (circadian, circannual)
- not aggravated by physical activity, no nausea associated with lacrimation, ptosis, restlessness, agitation
- attacks are preceded by yawning and tiredness

Question 83

Describe the epidemiology of cluster headaches

Answer 83

3-7 times more frequent in females than in males (the female-male ratio
changed in favor of females in past few decades)
about 10% of patients develop a chronic cluster headache without periods of remission

Question 84

Describe the symptoms of tension-type headaches

Answer 84

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

Question 85

Describe the epidemiology of tension-type headaches

Answer 85

• > 60% life prevalence, becomes chronic form in 3% of population
• peak of TTH is between 30-39 years
• educational level is positively associated with TTH
• Caucasians have greater prevalence of TTH than African Americans

Question 86

Give some of the acute provoking factors in headaches

Answer 86

Stress: periods of stress may induce headache attacks.

Sleep: headache patients report poor sleep, insomnia, wake up unrefreshed. Sleep apnea syndrome contributes to headaches.

Hormones: abrupt fall of estrogen level (pre-menstruation, menopause) is associated with headaches. Administration of estrogen-based contraceptives may also initiate an attack of headaches.

Diet: sparse data. Chocolate in some individuals may probably trigger headaches. Alcohol evokes attacks of cluster headache within an hour.

Question 87

Describe the symptoms and etiology of trigeminal neuralgia

Answer 87

Painful disease of older age (usually occurs at the age 50-70) with slight preponderance in women.
Etiology: compression of the trigeminal nerve (5th cranial nerve), usually by the superior cerebral artery.
Pain is electric shock-like, stabbing and unilateral, and paroxysmal (lasting from seconds up to 2 min).
Patient’s face can get distorted (“freeze”), patient may cry
Pain is elicited by a trigger: chewing, touch, talking, swallowing, therefore patients may lose weight by avoiding eating.
Allodynia - patients may stop washing their teeth/face or shaving
Treatment success is good with decompressing the nerve

Question 88

Describe and explain the effect of spinal cord lesions

Answer 88

usually as the result of trauma to the spinal cord.
Often associated with phantom sensations from regions below the level of injury.

Question 89

Define and give some types of central pain

Answer 89

• Lesions in the CNS
• Spinal cord lesions, brain lesions

Question 90

Describe and explain the effect of brain lesions

Answer 90

stroke (bleeding) leading to the damage of thalamus,
brainstem, subcortical white matter (e.g., spino-thalamic tract) and cortex

Question 91

Give some symptoms in central pain

Answer 91

1. Spontaneous and steady pain (e.g., aching, cramping, crushing, burning).
   
   2. Spontaneous neuralgia (shooting pain).
   3. Allodynia.

Pain seldom subsides by itself, but its quality changes over time.

Question 92

Give some examples of central pain conditions

Answer 92

Thalamic syndrome (central post-stroke pain): a lesion usually in contralateral thalamus but also in medulla or elsewhere. Wide range of pain qualities (e.g. burning, tearing, icy, pricking, or cutting).

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

Syringomyelia - a cyst filled with fluids in the
spinal canal compressing nerves and tracts,
causes bilateral pain in arms, shoulders, and thorax

Question 93

Describe the characteristics of fibromyalgia

Answer 93

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

Question 94

Give some of the symptoms of fibromyalgia

Answer 94

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 ,
      
      • having tenderness in 11 out of 18 points supports
        the diagnosis of FMS.

Other symptoms:
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.

Question 95

Describe the structural brain changes in fibromyaglia

Answer 95

FMS patients show shrinkage of the brainstem and reduction of brainstem volume which correlates with their sensitivity to pressure

Question 96

Give three types of arthritis pain

Answer 96

Pain related to malfunction at the join
osteoarthritis
rheumatoid arthritis
gout

Question 97

Describe the etiology and symptoms of oesteoarthritis

Answer 97

Progressive loss of articular cartilage leading to joint pain and limitation
of movement. OA present in 50% people > 75 years; obesity is a risk factor.

Pain is aching, occurs mostly during movement.
Stiffness of the joint is a frequent sign. At later stages, pain may sustain
during sleep, and later even in the resting periods following activity.

Question 98

Describe the etiology, symptoms and prevalence of rheumatoid arthritis

Answer 98

Inflammatory polyarthritis, various joints in a symmetric fashion.
Joints are swollen, tender and warm.
RA often caused by an increased autoimmune response.
Other symptoms: fatigue, loss of weight, subfebrilia,
morning stiffness.
Females show 3× larger prevalence of RA than men.

Question 99

Describe the etiology, symptoms and prevalence of gout

Answer 99

Metabolic disease associated with increased serum level of urate ions that accummulate in the joint and eventually destroy the cartilages.
Pain often occurs in the metatarsal joint of the great toe (podagra).
A gout attack starts in early morning hours, and peaks after 24 hours.
The joint is red and swollen. One attack lasts about two weeks.

Question 100

Describe the symptoms, etiology and prevalence of IBS

Answer 100

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

More prevalent in females than males (2-2.5 : 1), usually occurs at the age of 30-50 years.

IBS is frequently associated with fibromyalgia, and with psychiatric syndromes (somatisation, hypochondriasis).

Question 101

Give some of the potential mechanisms of IBS

Answer 101

Possible mechanisms (unclear):
Peripheral: increased gut motility, mucosal inflammation.
Central: dysregulation of the sympathetic and/or parasympathetic nervous
system.

Question 102

Describe research findings of brain structural changes in IBS

Answer 102

-The brain activations in anterior cingulate cortex were stronger in this and the rest of patients compared to the controls. But unclear if this is due to peripheral or central factors.

Question 103

Describe the symptoms, etiology and prevalence of burning mouth syndrome

Answer 103

Painful sensations in oral cavity (hard palate, tongue, lips and other parts of the mouth).
Pain is associated with disturbances of taste, and with sensations of dryness in the mouth (normal secretion of saliva, though).
Pain is less frequent in morning hours, increases through the day.
Emotions/stress and fatigue increases burning painful sensations.
Mental work and cold stimuli decrease pain.
Prevalence: larger in females than in males.
Etiology: unknown – interactions of central and peripheral mechanisms?

Question 104

Give some reasons for pain assessment

Answer 104

• therapeutic decisions
• progress of therapy
• evaluation of effects of different treatments
• individualised pain therapy (phenotype of patients)
• insurance, compensation, legal issues
• identifying the presence of pain in vulnerable people (e.g people with communication disorders)

Question 105

Give some of the possible markers of pain

Answer 105

• brain thresholds
• self-reports (e.g McGill Pain Questionnaire)
• behavioural measures (pain behaviour, facial expressions)
• brain and autonomic changes

Question 106

Define pain threshold

Answer 106

Minimum amount of stimulation that reliably evokes a report of pain

Question 107

Define pain tolerance threshold

Answer 107

Time that a continuous stimulus is endured, or the maximum tolerated intensity

Question 108

Give some methods of examining pain threshold

Answer 108

• Method of limits: series of ascending and descending stimuli
• start from a low level and ascend until the stimulus turns into a pain
• Marstock’s modification - adaptation for testing thermal pain
• Most common method
• Method of adjustment: allows participant to tune the stimulus intensity to painful level
• Method of constant stimuli: stimuli of fixed intensity are presented in random order (gets rid of expectancy effects)

Question 109

Describe methods of testing pain tolerance

Answer 109

• Cold pressor test
  - endures cold pain

-Tourniquet ischaemia
- ischaemic blood
- can use blood pressure cuff

Question 110

Describe and explain quantitative sensory testing (QST)

Answer 110

• Can test: warm, cold, heat pain, cold pain (electrical thermode needed) and vibration threshold
• training needed to deliver

+ diagnostic value
+ phenotyping patients based on their QST profiles
- does not measure spontaneous background pain

Question 111

Give some advantages and disadvantages of pain threshold testing methods

Answer 111

+ simple to administer
+ pain expressed in physical units

• not suitable for clinical pain
• depends on reaction time
• response bias: “stoic” style of responding

Question 112

Give some of the response dependent measures of self-report instruments

Answer 112

• categorical scale (no-yes, (no,mild,strong)
• verbal scales
• numerical scales
• visual analogue scales
• combined verbal-numeric instruments

Question 113

Describe and explain numerical rating scales

Answer 113

• ordinal scale: a number is assigned to pain
• simple to use, suits well for rapidly changing pain, sensitive to pain intensity
• but boundaries between categories are not known and are only assumed to be equal
• tendency towards stereotyped response (e.g getting fed up and always answering with 10)

Question 114

Describe and explain direct magnitude scaling (visual analogue scales)

Answer 114

• ratio scales - pain is represented as continuum that is matched with another modality
• subjects are given a reference continuum (intensity of sound, line, length of line etc.)
• position of reported pain is proportional to pain continuum

Question 115

Give some of the advantages and disadvantages of visual analogue scales

Answer 115

+ true ratio-based scale
+ easy to administer and score
+ sensitive to variations of pain due to therapy interventions

• unidimensional
• sometimes low reliability
• some patients do not understand the scale
• subject to bias (tendency to use full range of scale)

Question 116

Describe and explain the McGill Pain questionnaire

Answer 116

• Melzack
• 78 pain words organised into 20 categories
• present pain intensity
• location of pain

MEASURES
- PRI = pain rating index (rank values of the words)
-Sensory dimension: categories 1-10
- Affective dimension: categories 11-15
- Evaluative: category 16
- Miscellaneous : categories 17-20
- the number of words chosen
- present pain intensity (0-5)

Question 117

Explain the reliability and validity of the McGill Pain Questionnaire (MPQ)

Answer 117

Reliability
MCQ confirmed to be reliable (test-retest, split-half reliability)
sensory categories: >0.7, affective, ~0.6, evaluative, total ~0.85
(Kilminster and Mould, Int. J. Pharm. Med., 2002)

Construct validity
factor analysis studies confirmed multidimensionality of MPQ
Donaldson (Pain, 62: 101-109,1995) … 3 factors
Reading et al. (1979) .. 4 factors
Holroyd et al. (1992) … 4 factors
Crockett et al. (1977) .. 5 factors
Turk et al. (1985) ……. 3 classical factors

Question 118

Describe the short-form MPQ

Answer 118

15 representative words
(11 from sensory and 4 from
affective categories)
Takes less than a minute to fill

Question 119

Describe and explain behavioural assessment methods

Answer 119

Pain manifests in behavioural changes (acquiring help, giving a sign of warning)

Pain behavior: any behaviour informing that pain is being experienced (Fordyce, 1976)

Behavioural analysis:
helps to pinpoint the pain problem
enables to set the baseline level of behaviour against which the effects of treatment will be compared
predicts the patient’s response to therapy

Question 120

Give some types of pain behaviour

Answer 120

Facial expressions
verbal pain statements
reduced social interactions
use of support (cane or walker)
guarding = cradling, interrupted movements
rubbing
avoiding the use of a limb where otherwise appropriate
bracing = pain avoidant, stiff posturing

Question 121

Give some of the observation methods for quantifying pain behaviour

Answer 121

Continuous observation of the whole behaviour in a variety of situations
+ complexity and stream of behavior

-   time consuming and expensive
-   complicated data analysis (scoring)

Duration measure: time spent demonstrating behaviour

Frequency counts: number of instances of each target behaviour

Good inter-observer reliability, bad test-retest reliability

Question 122

Give some of the advantages of using behavioural methods

Answer 122

+ useful to pinpoint important features of pain
+ can be realised in natural settings
+ unbiased

• time consuming
• need observer training
• ethics - complement rather than replace the self-report instruments

Question 123

Explain Darwin’s findings on facial expressions on pain

Answer 123

• 1872
• facial pain expressions: patterns of facial activity modified by social and family influences
• less dependent on subjects willingness to admit pain
• not confound by labels or abstract concepts

Question 124

Give some facial expressions of pain in adults

Answer 124

Brow lowering

Narrowing of the eye orbit

Raising the cheek

Eyes closed or blinking

Raising the upper lip

Parting the lips or dropping the jaw

Question 125

Describe the facial action coding system

Answer 125

Facial Action Coding System (Ekman and Friesen, 1978) is used to measure Action Units (small movements of facial structures) in an objective manner.

New methods (e.g., Machine learning) utilize FACS to evaluate pain or emotional representations in facial expressions.

Question 126

Explain why pain assessment is important

Answer 126

Which conditions represent risk of unreported pain suffering:
Immaturity: Infants, toddlers, preschool children (Lecture 8).
Disability: Down’s syndrome, Alzheimer disease (Lecture 8), cerebral palsy, multiple sclerosis.
Temporary or permanent restriction of consciousness: general anesthesia, intoxication, sedatives, disturbances of consciousness
4. Inability to communicate: language deficits, mutism, ASD

Cerebral palsy is a serious problem associated with pain. CP occurs in about 0.2% of population. CP results from pre/peri/post-natal trauma leading to damage of motor brain regions. It manifests in strong muscle contractures that may cause severe pain. The symptoms may progressively worsen over life time. CP is associated with serious cognitive impairment in 30% of cases. Such patients cannot report their pain, although behavioural signs clearly reveal the presence of pain.

Question 127

Describe and explain pain in disturbances of consciousness

Answer 127

Unresponsive wakeful state. A state of partial arousal without self awareness (eyes track moving objects, swallowing, smiling, grunting, moaning in absence of external stimuli)
Can be classified according to duration, Persistent/Permanent

Common causes: traumatic brain injury, neurodegenerative disorder, and congenital abnormities of the brain

Question 128

Describe the nociceptive coma scale

Answer 128

• Schnacker et al., Pain, 2010
• brief evaluation (1-2 mins) of patient’s behaviour at rest or during nociceptive stimulation

Question 129

Describe the potential consequences of poor pain assessment

Answer 129

• Risk of under-assessment and under-treatment
  
  • death due to intestinal obstruction 34x more frequent in people with intellectual disabilities (Roy and Simons, 1987)
    - people with cognitive deficits receive less medication (Kaasalainen, 1998)
• Risk of overtreatment if the level of pain is overestimated
• Untreated pain in people who are unable to communicate pain may worsen their cognitive abilities and executive functions

Question 130

Describe how pain scales can be simplified

Answer 130

About 35% of people with cognitive deficits cannot understand the question during taking self-reports of their pain

Simplified scales, adapted from those assigned for children can help in acquiring self-reports persons with communication disorders

Question 131

Describe how observation can be combined with questionnaires to assess pain in patients with communication/ language deficits

Answer 131

Focusing on units of pain behaviour using validated observational scales:

PACSLAC, DOLOPLUS: specialised observation scales to assess pain in patients with dementia (on CANVAS > Lecture week 3 > Supplementary materials)

CHEOPS : Children’s Hospital of Eastern Ontario Pain Scale (McGrath et al., Adv. Pain Res. Ther., vol. 9, pp 395-402, 1985)

DEPS: Dalhousie Everyday Pain Scale (Fearon et al., Pain, 68: 55-62, 1996) is a short instrument enabling to collect reports of caregivers about intensity of distress, anger, protective behaviour (holding, favouring), and social response.

FACS: (e.g. LaChapelle et al., Clin. J. Pain, 15: 13-23, 1999)

Question 132

Give rules for pain assessment and pain management in nonverbal people

Answer 132

Facilitate self-reports in those patients who can respond non-verbally (nodding,
eye blinks)

Identify sources of pain which in other people would cause pain (leads, tubes, monitoring devices), and check if a patient had a pre-existing pain condition (e.g., osteoarthritis)

Consult any symptoms of pain and changes in mood with a family members, caregivers, and other health care professionals

Observe indicators of pain (facial, mood, movements, behavioural scales useful)

If clear signs of pain present, initiate an analgesic trial (e.g., analgesic drugs

If the analgesic trial confirmed pain being present, a collaborative pain treatment plan should be designed

Question 133

Define sex and gender

Answer 133

Canadian Institute of Health Research (2022):
Sex is often associated with biological factors, such as genetics, sex hormones, and physiology, and usually involves comparisons between men and women. Conversely, gender is associated with psychological and sociocultural factors, such as beliefs, expectations, and stereotypes, and how men and women behave and interact with one another. Binary categories are commonly used (e.g., male/female, man/woman, and boy/girl), although gender is not constrained to this and encompasses broader aspects”

Question 134

Give some research findings into sex differences in pain

Answer 134

Chesterton et al. (Pain, 101: 259-266, 2003) analysed differences in pressure pain threshold (pressure on the interossei muscles - back of hand).

Men required greater levels of mechanical pressure to elicit pain response

Pain threshold differences were stable over one hour period

Question 135

Explain meta-analysis findings into sex-based pain differences

Answer 135

Pain thresholds lower, pain endurance shorter in females than males.

Riley et al. (Pain,74:181-187, 1998)
Meta-analysis of 21 studies analysing differences between females and males in experimental pain threshold and pain tolerance.
Largest differences in pain thresholds and pain tolerance for electrical and pressure stimulation: males showed higher thresholds than females.
The mean effect size over different types of stimuli was 0.55 and 0.57 for pain threshold and pain tolerance, respectively.
Authors calculated sample sizes required for these size effects; the groups should count at least 41 subjects each. Thus, early studies that have not reported statistically significant differences might suffer from low power.

N.B.: Greenspan and Taub (2013) performed a similar calculation including newer studies and raised the recommended cohort sizes to 49

Question 136

Describe Racine et al.’s review (1998-2008)

Answer 136

Racine et al. (2012 Part 1) analysed 172 papers on sex differences in experimental pain over a 10 year period with a systematic literature review:

Pain threshold, pain tolerance, pain intensity:
no consistent differences in pain intensity (debateable) or pain thresholds in various pain modalities

pain tolerance was greater in males than females for cold (in 81% of studies), heat (80%), and pressure pain (86%)

low statistical power in many studies

Question 137

Describe Mogil’s findings (2012)

Answer 137

Re-analysis of 122 studies originally reviewed by Racine et al. (2012).
The number of studies showing increased pain threshold and pain tolerance in males compared to females is much larger than for a reverse direction.

Question 138

Describe Greenspan and Taub’s findings (2013)

Answer 138

Data on pain sensitivity were derived from the large scale OPPERA study (+4000 ppts) which considered males and females.

Among the most sensitive 10%, 83% are women.

A 4.8 times greater proportion of females than males among 10% of pain most sensitive people

Question 139

Describe sex differences in conditioned pain modultion

Answer 139

A painful conditioning stimulus (e.g., water of 1˚C) in one loci will attenuate the pain associated with the test stimulus in another location.

A non-painful conditioning stimulus (e.g., water of 30˚C) will not attenuate the pain associated with the test stimulus on opposite hand

The drop in pain ratings to the test stimulus under a painful and non-painful conditioning stimulus is the measure of conditioned pain modulation

Conditioned pain modulation activates the endogenous opioid system and inhibitory synapses in spinal cord dorsal horn neurons

Popescu et al. (2010) reviewed 17 studies comparing effects of pain modulation in males and females
males showed stronger inhibitory control of pain intensity in most studies less clear differences in pain threshold and spinal reflexes
Males activate m-opioid receptors during pain more strongly than females
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Question 140

Describe the relationship between hormones and pain

Answer 140

Increased levels of Oestrogen in females is associated with increased pain threshold

Meta- analyses indicate no convincing data on differences in pain sensitivity in females taking or not taking oral contraceptives (Racine et al., 2012/2; Greenspan and Taub, 2013)

Hormonal replacement therapy (HRT) in menopausal period:
smaller experimental pain in females receiving HRT than those not receiving (Racine et al., 2012/P2)

Question 141

Describe the relationship between the menstrual cycle and pain

Answer 141

Meta-analysis of 19 pain studies (Riley et al., Pain, 81: 225-235,1999):
Pain thresholds for pressure, and cold pain were greater in follicular than in luteal phase.

Pain type specific? Painful electrical stimulation yielded contradictory results.

None of 12 studies performed since 1998 has reported any effect of MC on pain intensity or pain thresholds (Racine et al., 2012/2)

MC effects on conditioned pain modulation (Rezaii et al., J. Pain, 2012) suggest greater pain inhibition during ovulation period

Pressure pulses (test stimuli) to masseter muscle during concurrent cold pressor (5 min, conditioned stimulus) pain in contralateral arm in 3 periods of MC (early follicular, ovulatory, mid-luteal)

No effects of MC on cold pressor test – MC appears to modulate only the inhibitory mechanism

Question 142

Describe sex-related differences in brain activations in males and females

Answer 142

Straube et al. (HBM, 2009) applied painful electrical stimuli to the dorsum of the hand in males and females. Females had greater activation in the medial pre-frontal cortex – shown below pain threshold and related to pain anticipation,

Males showed more activation in anterior insula.

Greenspan and Taub (2013) summarised results of 11 brain imaging studies in experimental pain

Variable patterns of activations across studies, with perphaps only insula consistently yielding greater activation during painful stimulation in males than females

A methodological problem: stimulus intensity was matched to be subjectively identical in males and females but only in some of the studies

Question 143

Describe sex-related differences in clinical pain

Answer 143

Females compared to males:

1. have greater prevalence of chronic pain syndromes.
2. experience more intense pain for comparable pathology (e.g. injury, surgery).
3. show stronger analgesia after administration of opioids

Fillingim et al. (2009)
There are types of pain which do not show sex differences, e.g., cancer pain

Question 144

Describe sex-related differences in acute pain

Answer 144

More female patients exceeded the criterion for Pain and delayed recovery P < .001. Phillips et al., (2003)

Gender and anxiety levels influences postoperative pain: (2020) Liang Xu & Xia

Question 145

Describe sex-related differences in post-operative pain

Answer 145

Tighe et al. (2014) analysed sex differences in post-operative by collecting numerical rating scales (0-10) in 330,000 patients in Florida over one year.

Serious surgeries: amputations, cardio-thoracic, orthopedic.

Measures: severe pain events mean pain etc.. From day 1 to 5 post-operatively.

In all pain measures, females had larger scores than males e.g., day 5 : statistically significant difference with a mean score of 4.1 (99% CI 4.1–4.1) for females and 3.74 (99% CI 3.7–3.8) for males

Question 146

Describe sex-related differences in pain relief using opioids

Answer 146

Chia et al. (Can. J. Anesth. 49: 249-255, 2002) analysed the consumption of morphine in the regime of patient-controlled analgesia.

2298 patients undergoing abdominal, chest or limb surgery. Consumption of opioids was screened from 12 to 72 hours post-operation.

Males take higher dose BUT…

Campesi et al. (2012): Females require less opioids than males to reach comparable level of analgesia

Question 147

Describe meta-analyses findings of opioid analgesia in males and females

Answer 147

Morphine induces greater opioid analgesia in females than males in experimental pain
Patient-controlled analgesia shows reduced morphine doses in females than males
The longer the analgesic intervention, the larger the differences between males and females.

Question 148

Describe sex-related differences in problematic opioid usage

Answer 148

Serrdarevic (2017) evaluated gender studies of opioid use (8 total) and data from +8000 people in a health engagement program in USA.
Half reported use of prescription opioids

USA gender prevalence review of studies: Women are more likely to use prescription opioids compared to men.

Health data outcome: females significantly higher usage of opioids in past and present.

Question 149

Describe sex-related differences in non-pharmacological pain relief

Answer 149

Keogh et al. (Pain, 2005) reported inferior outcomes for females, relative to males, following interdisciplinary chronic pain management programs.

This was replicated in analysis of PMP treatment for veterans in the USA (shown is pain related fear but result was also similar for pain outcomes). Murphy et al., 2016 JRRD.

Question 150

Describe individual gender factors in pain

Answer 150

Wise et al. (Pain, 96:335-342, 2002) analysed pain thresholds and pain tolerance thresholds in males and females. They used the Gender Role Expectations of Pain questionnaire (GREP) to measure gender-specific expectations about pain (willingness to endure and communicate pain).

GREP was a significant, although not exclusive, predictor of pain tolerance and pain threshold in cold pressor test.

Pool et al. (Pain, 2007) administered questionnaires to measure how males and females identified themselves with “ideal men” or “ideal women” roles.

Greater experimental pain tolerance in men identifying with traditional male roles, compared with women identifying with traditional female roles

Question 151

Describe stereotypical beliefs in pain treatments

Answer 151

Stereotypes can be damaging, e.g., men are considered less expressive and more likely to engage in avoidance when in pain, whereas women are perceived to be more likely to catastrophize and cry (Keogh, 2022).

Hirsh et al., (2208): when viewing virtual patients, observers rated women as having more pain and being worse at coping.

Schafer et al., (2016) found that female patients were viewed more negatively in clinical scenarios (lower table) relative to males.

Question 152

Describe evolutionary perspective in sex and gender differences

Answer 152

Females might have an additional antinociceptive circuit that is being implemented during childbirth, and this pattern might interfere with the default pain processing mode leading to greater pain.

Males have been exposed more frequently to injuries, and natural selection contributed to affirmation of less sensitive pain genes.