Chronic Pain

Question 1

Chronic non-cancer pai

Answer 1

Heterogenous physical and psychological condition that
can have a significant impact on physical ability,
emotional well-being, and quality of life
May be pain that
● Persists beyond normal healing time
● Relates to chronic degenerative disease or persistent
neurologic condition
● Emerges and persists without an identifiable cause
Lots of conditions that fall under chronic pain

Question 2

Pathophysiology - Revisited

Answer 2

Dysfunctional pain
or
Nociplastic pain

No known structual NS lesion
Or active periph inflaamm
Spontaneous pain with lack of stimulus, pain with non-painful stimuli
Maladaptive and potentiall persistent

Chornic pain often amix of nociceptive, nociplastic, neuropathic pain

Question 3

Populations that bear more of the chronic pain
burden include

Answer 3

● Older adults
● Women
● Indigenous Peoples
● Veterans
● People who use drugs

Question 4

Risk Factors

Answer 4

● Psychological vulnerability
(catastrophizing)
● Anxiety or depression
● Female sex
● Younger age (adults)
● Genetic predisposition
● Inefficient diffuse noxious
inhibitory control (DNIC)

● Descending pathway of pain
inhibition
● Nerve damage due to injury
or surgery
● History of poor acute pain
management
● History of poor response to
common analgesics

Question 5

Complications

Answer 5

Chronic pain often presents as a complication of other
disease states, but may also result in its own complications:
● Deconditioning
● Hormonal effects
○ e.g., excess catecholamine production
● Neuropsychiatric symptoms
○ e.g., insomnia, memory loss, cognitive decline, depression

Overactivation of symp nervous system
Adrenaline release combined with cortisol
More anxiety or dread

Question 6

Chronic Low Back Pain
3 trajectories

Answer 6

Low back pain is the leading cause of disability in the
world
One of the most common reasons that patients seek
care and a top reason for early retirement and
income poverty

3 trajectories: first is it quickly moves towards a state of no or very little pain

Ongoing moderate pain, fluctuating
- Variable intensities that wax and wane
Constant severe pain, persistent trajectory

Question 6

There are many potential causes of low back pain

Answer 6

● Mechanical
○ e.g., degenerative joint disease, herniated disk, vertebral #, etc
● Non-mechanical spinal conditions
○ e.g., cancer, infection, inflammatory arthritis, etc
● Visceral disease (non-spinal disease with referred pain)
○ e.g., prostatitis, pelvic inflammatory disease, pancreatitis, etc
The majority of the time in chronic low back pain, there is
no identifiable active cause – but should still assess for
red flags`

Intiial assement for pt who may hve srious pathology or barriers to recovery and those that need further intervention

Question 7

Chronic Low Back Pain
red flags

Answer 7

possible fracture: major trauma, such as MVA or fall from height

possible tumor or infection: recent fever chills unexplained weight loss
possible cauda equina syndrome: saddle anesthesia, numbess, recent onset of bladder dysfxn, sudden bilteral leg weakness

NIFTI
Tumor, infection

Question 8

yellow flags

Answer 8

Psychosocial barriers
to recovery

belief that pain and activity are harmful
sickness behaviours
low or neg moods

see slide 13

Question 9

Chronic Pain - Assessments

Answer 9

Accurate diagnosis
Identify iatrogenic factors
Psychiatric and psychosocial assessment
Gather the pain history

Question 10

Goals of Therapy

Answer 10

● Treat underlying cause of pain
● Reduce pain
● Improve quality of life
● Improve function
● Improve other symptoms associated with pain
○ Sleep, mood, etc

What sort of tings would you like to do
If you give them opioids, tey may not be very functional

Question 11

Treatment Algorithm

Answer 11

Using low back pain as
an example

Lots of diff nonpharm for perisstent nonspecific
As meds may not give as much benefit
nopharm more benefit, trial and error largely

Question 12

Treatment AlgorithmNon-pharmacologic
Treatment

Answer 12

Self-management programs
● Activity
● Relaxation techniques
● Communication skills
● Modification of negative “self-talk” or
catastrophizing

● Education
● Sleep hygiene
● Stress management
● Cognitive behavioural therapy
● Physiotherapy
● Tai chi

Congitive is recommended commonly for psych therapies
Execise is beneficial for function, a bit for relief of pain

Small size effect for exercise
Potential for harm with spinal manipulation

Moderate effect with cognitive therapy

Question 13

peer simplified chronic pain guidelne

Answer 13

slide 21

Question 14

4 ps in pain manageent

Answer 14

prevention, psych, physical, pharmaceutical

musc therapy
Some evidence both mechanistic and otherwise
May help mitigate pain

Question 15

Pharmacologic
Treatment
Tricyclic Antidepressants

Answer 15

Nortriptyline → Initial: 10 mg PO hs
Usual: 10-50 mg PO hs
Desipramine
Amitriptyline → Initial: 10-25 mg PO hs
Imipramine Usual: 25-100 mg PO hs
Start low and increase dose slowly (q1-2ks)
Adequate trial: ~2-4 weeks at adequate target dose

Initae one agent at a time not multiple
Nortriptyline secondary amine
Amitryptiline teritary

Secondary is less anticholingeric, better tolerated
Dont need to memorize dosing

Question 16

Tricyclic Antidepressants
Evidence:

Answer 16

Neuropathic pain → NNT =3 (≥ 30% pain improvement)
NNH = 13 (ADR causing withdrawal)
30% pain improvement at least is minially clincally important

Chronic low back pain → may not significantly improve
pain or disability
Amitriptyline most studied, but nortriptyline generally
better tolerated
If there is NP componetnt (often there is), TCAs can be cisb==bsudered (prefered over trial of opioids)

Question 17

Tricyclic Antidepressants
Adverse effects

Answer 17

● Drowsiness/sedation
● Confusion
● Dry mouth
● Hypotension
● Constipation
● Urinary retention
● Weight gain
27
● QTc prolongation/arrhythmia

2-3 hours before bedtime
Minimze residual sedation in the morning
In the AM

Unintentional overdoses not common
Low risk of seizures at therapeutic dose, at setting of OD risk is higher for seizures

Question 18

Serotonin-Norepinephrine
Reuptake Inhibitors

Answer 18

Duloxetine → 30 mg PO once daily x 1 week, then
60 mg PO once daily
Venlafaxine XR → 37.5 mg PO once daily x 4-7 days,
then 75 mg PO once daily
(may need to get to 150-225 mg/d for benefit)
Allow ~ 1 week at each dose for tolerability
Adequate trial: at least 2-4 weeks at effective dose

Can go higher in these dosing ranges, haven’t seen much additional benefit for it above 60mg
More AE

150mg at least for benefit of pain, more NE kicks in
Better for bpain if you hit 5-HT AND NE
Duloxetine has higher NE activity at standard doses
Venlafaxine has higher 5HT activity, neeed higher dose to hit NE

Question 19

Serotonin-Norepinephrine
evidence
Reuptake Inhibitors

Answer 19

Duloxetine
Chronic low back pain → NNT 7-8 (30-50% pain improvement)
NNH 6-12 (discontinue due to AE)
Also effective for other pain presentations
Venlafaxine
Evidence is scant

Magnitude of benefit varies

Usually not life threatening AE but du to tolerance, dizzine
Pt start on lower dose for tolerance reasons

Duloxetine better evidence usually preferref for chronic pain

Question 20

Serotonin-Norepinephrine
Reuptake Inhibitors
Adverse effects

Answer 20

● GI
● Nausea
● Dry mouth
● Dizziness
● Sleep disruption, take in AM
Seizure risk with toxic doses
Risk of sertoonergic syndrome

Duloxetine is a moderate 2d6 inhibitor, venla is mild inhibitor

Drug Interactions
● Pharmacodynamic
○ Serotonergic
● Pharmacokinetic
○ CYP 2D6 (substrate + inhibitor)
○ CYP 3A4 (venlafaxine) (substrate)
○ CYP 1A2 (duloxetine) (substrate)

Question 21

Gabapentinoids

Answer 21

Gabapentin → Initial: 100-300 mg PO HS (or 100 mg TID)
Increase by 100-300 mg per day (or weekly)
Usual: 600 mg PO TID-QID
(may require at least 900 mg/d for benefit)
(at least 1800 mg/d often needed in trials)
Pregabalin → Initial: 50-75 mg PO BID (or 25-50 mg TID)
Increase to 150 -300 mg PO BID
Titrate every 3-7 days, as tolerated, until at effective dose
Allow 1-2 weeks to assess benefit and tolerability
31 Adequate trial = ~3-4 weeks on adequate dose

KNOW MINIMUM EFFECTIVE DOSE = 900MG
Start 100-200 and slowly increase to it

Can go up to 3.6g/day
2.4g/day - usually would not be pushed further

More easy to dose; start dosing ranges where likely to be beneficial
300mg PO BID is max, 250mg is sweet spot w good ad==efficacy
Slow.ly weaned as can have withdrawal effect

Question 22

Gabapentinoids
Evidence

Answer 22

Gabapentinoids may not improve pain or disability in
chronic low back pain and may increase risk of AEs
● DB, PC, RCT, N=108 from primary care/community settings
○ 67% F/U at 12 weeks
○ No significant difference in pain improvement or disability improvement.
Marked AEs gabapentin 55% vs placebo 32%
○ Pain. 2016;157(7):1499.
● SR → 3 RCTs (N=100) gabapentin vs placebo for lower back pain (+/- radiating
leg pain). No significant difference in pain improvement within 3 months

Chronic low back pain with opioids → may increase risk of
opioid-related deaths.
Neuropathic pain
● Gabapentin → NNT 7; NNH 8
● Pregabalin → NNT 5-8; NNH 14

Some benefit
If there is NP component - more likely to get benefit from gabapentinoid on board

Publication bias - exagerated beneif==fits from gabapentin

Question 23

Gabapentinoids
Adverse effects

Answer 23

● Dizziness*
● Somnolence*
● Weight gain (? pregabalin > gabapentin)
● Euphoria/abuse (? gabapentin > pregabalin)
● ? ↑HF (dose-dependent ↑ peripheral edema)

More abuse potential w gabapentin, snort or inject at high dose

Not sure if cause edema or HF
No known metabolism interactions, there are both renally cleared
Check renal fxn if impaired

Question 24

Topiramate

Answer 24

Initial: 25 mg po HS
Usual: 100 mg po BID (or 50 mg AM, 100 mg HS)
Increase dose weekly
Evidence
Chronic low back pain → may improve pain in short
term (very limited evidence)

Antiepiliptic
More in migraine prevention
Small dose then increased weekly
Scant evidence for it
CI may be beneficial or may cause harm

Question 25

Topiramate
Adverse effects

Answer 25

● Drowsiness, dizziness, fatigue
● Ataxia, tremor
● Paresthesia
● Difficulty word-finding
● ↓ concentration
● Other non-CNS adverse effects

Lots of CNS AE