WEEK 5: Pain: Management
Types (how they differ):
Acute pain: sudden, short duration; protective; sympathetic signs (↑HR, ↑BP). Treat cause + short-term analgesia.
Chronic pain (>3 mo): persists beyond healing; biopsychosocial; goals = function/QOL; avoid long-term high-dose opioids.
Nociceptive pain: tissue injury/inflammation.
o Somatic: well-localized, aching (skin, bone, joints).
o Visceral: diffuse, cramping/pressure (organs), may refer.
Neuropathic pain: nerve injury/dysfunction; burning, shooting, tingling, allodynia; responds best to adjuvants (SNRIs,
TCAs, gabapentinoids).
Malignant (cancer) pain: often mixed (nociceptive + neuropathic); prioritize comfort, use WHO ladder more liberally.
Non-pharmacologic approaches (use with meds in all patients):
Education, goal-setting, CBT, mindfulness
Physical therapy, graded exercise, heat/ice
TENS, acupuncture, spinal manipulation
Sleep hygiene; weight loss; ergonomics; pacing; splints/braces
WHO 3-step ladder (with examples)
Step 1 – Mild pain: non-opioids ± adjuvants
APAP, NSAIDs (e.g., ibuprofen, naproxen); topicals (diclofenac gel, lidocaine patch); adjuvants if neuropathic.
Step 2 – Moderate pain: weak/short-acting opioids + Step 1 ± adjuvants
Tramadol or low-dose short-acting opioid (hydrocodone/APAP, oxycodone IR) + NSAID/APAP.
Step 3 – Severe pain: strong opioids + Step 1 ± adjuvants
Morphine, hydromorphone, oxycodone, fentanyl, methadone; consider nerve blocks, spinal analgesia in cancer pain.
Use validated pain scales (NRS 0–10; Figure 35-1) and follow a stepwise algorithm (Figure 35-2; Table 35-1 aligns analgesic
selection with pain intensity).
NSAIDs
MOA: inhibit COX-1/COX-2 → ↓ prostaglandins → ↓ peripheral/central sensitization (analgesic, anti-inflammatory, antipyretic).
Indications: inflammatory nociceptive pain (musculoskeletal, osteoarthritis, sprains, dysmenorrhea).
Precautions/adverse effects:
GI irritation/ulcer/bleed (↑ risk with age, steroids, anticoagulants)
Renal vasoconstriction → AKI, Na⁺/H₂O retention; avoid in advanced CKD
CV risk (MI/stroke), ↑ BP; naproxen may have the most favorable CV profile
Platelets: nonselective NSAIDs inhibit TXA₂ (reversible); ibuprofen can blunt aspirin’s antiplatelet effect (separate dosing)
COX-2 (celecoxib): ↓ GI risk, but caution in CV disease
Is one NSAID safer/better?
Analgesic efficacy is similar at equipotent doses; choose by patient risk: GI (consider PPI or COX-2), CV (avoid
COX-2/high-dose diclofenac), renal (avoid class).
Ceiling effect: yes—once analgesic ceiling reached, higher doses ↑ toxicity without more pain relief (e.g., ibuprofen >400 mg/dose
gives little extra analgesia).
Special: ketorolac max 5 days (GI/renal risk).
Acetaminophen (APAP)
MOA: central prostaglandin (COX) inhibition → analgesic + antipyretic (minimal anti-inflammatory).
Indications: mild pain/fever; OA when NSAIDs risky; combine with other classes for multimodal analgesia.
Dosing/limits:
Typical adult: 325–1,000 mg q4–6h PRN
Absolute max: 4 g/day (all sources)
Many practices cap at 3 g/day (safer)
Older adults, liver disease, chronic alcohol use: keep ≤2 g/day, avoid if active severe hepatic disease.
1
,Precautions: hepatotoxicity (esp. with alcohol/fasting/overdose); check combination products.
Spectrum vs NSAIDs: APAP lacks anti-inflammatory effect; safer GI/renal profile when inflammation isn’t prominent.
Adjuvant analgesics (what & when)
Use when neuropathic features (e.g., DPN, PHN), fibromyalgia, central sensitization, or as opioid-sparing agents.
Antidepressants: SNRIs (duloxetine, venlafaxine), TCAs (nortriptyline, amitriptyline)
Anticonvulsants: gabapentin, pregabalin, carbamazepine (trigeminal neuralgia)
Topicals: lidocaine 5% patch (PHN), capsaicin
Muscle relaxants: tizanidine, baclofen (spasticity)
Others (specialist): ketamine (NMDA antagonist) in refractory pain; clonidine/dexmedetomidine (α2 agonists);
corticosteroids for cancer/bone pain or nerve compression
Opioids
MOA: μ-opioid receptor agonism (± κ/δ) → ↓ neurotransmitter release & postsynaptic excitability in pain pathways (spinal &
supraspinal).
Common adverse effects & management:
Constipation (no tolerance): prophylax with stimulant laxative (senna ± docusate) and fluids/fiber; refractory OIC →
peripherally acting μ-antagonists (PAMORAs: methylnaltrexone, naloxegol, naldemedine)
Nausea/vomiting: usually transient; ondansetron or prochlorperazine
Sedation: dose-reduce, space doses, consider stimulant in palliative settings
Respiratory depression: avoid rapid titration, caution with sedatives; naloxone for overdose
Pruritus: antihistamine or rotate opioid (often histamine-release with morphine)
Endocrine (↓ HPG axis), urinary retention, QT prolongation (methadone), opioid-induced hyperalgesia (consider dose
reduction/rotation)
Tolerance develops to most effects except constipation & miosis.
True opioid allergy (anaphylaxis) – reasonable alternatives:
Opioids fall into 3 main chemical classes—cross-reactivity is more likely within a class:
Phenanthrenes: morphine, codeine, hydromorphone, oxycodone, hydrocodone
Phenylpiperidines: fentanyl, meperidine
Diphenylheptanes: methadone
→ If true IgE to a phenanthrene (e.g., morphine), switch to a phenylpiperidine (fentanyl) or diphenylheptane (methadone)
and monitor.
Equianalgesic dosing, incomplete cross-tolerance, rotation
Equianalgesic dose: a dose of opioid B that provides ~the same analgesia as opioid A.
Incomplete cross-tolerance: when switching opioids, the patient is less tolerant to the new opioid → reduce the calculated
equianalgesic dose by ~25–50% (more reduction for high doses, frail/older adults), then titrate.
Example manual conversion (illustrative):
Patient takes morphine 60 mg PO/day (15 mg q6h).
Oral morphine : oxycodone ≈ 1.5 : 1 (approximate).
o 60 mg morphine/day ≈ 40 mg oxycodone/day.
Apply 30–50% reduction for incomplete cross-tolerance → new target 20–28 mg/day.
o Practical regimen: oxycodone IR 5 mg q6h (20 mg/day) with PRN rescue, reassess in 24–48 h.
(You’d choose different products/intervals to match patient factors and pain pattern.)
Always reassess pain, function, adverse effects, and total daily MME, and document goals/risks.
Quick reference: picking & protecting
Start with non-pharm + APAP/NSAID (if safe).
Add adjuvant if neuropathic features.
Escalate to short-acting opioid for breakthrough severe pain; convert to long-acting only when stable.
Bowel regimen from day 1 with any opioid.
2
, Revisit goals frequently; deprescribe/rotate as needed.
_________________________________________________________________________________________________Headaches
Migraine & Cluster Headaches — What to Know
1) IHS Classification (diagnostic criteria)
Migraine without aura
≥5 attacks lasting 4–72 h (untreated/unsuccessfully treated)
≥2 of: unilateral, pulsating, moderate–severe intensity, aggravated by routine activity
During HA ≥1 of: nausea/vomiting OR photophobia + phonophobia
Not better explained by another diagnosis
Migraine with aura
≥2 attacks with fully reversible aura (visual, sensory, speech/language; ± brainstem, retinal; motor aura may last longer)
≥3 of: gradual spread (≥5 min), ≥2 aura symptoms in succession, each aura 5–60 min (motor up to 72 h), ≥1 unilateral, ≥1
positive (scintillations/tingling), headache during aura or within 60 min after
Cluster headache
Severe/very severe unilateral orbital/supraorbital/temporal pain 15–180 min
Frequency: 1 every other day → 8/day during a cluster period
With ipsilateral autonomic signs (≥1): conjunctival injection/tearing, nasal congestion/rhinorrhea, eyelid edema,
forehead/facial sweating, miosis/ptosis and/or marked restlessness/agitation
2) Headache diary, triggers & red flags
Headache diary
Track date/time, duration, severity, associated symptoms, meds used/response, sleep, stress, menses, foods,
caffeine/alcohol, weather. Helps identify triggers & medication-overuse headache (MOH).
Common migraine triggers (Table 36-2 style)
Lifestyle: stress, let-down after stress, sleep loss or excess, skipped meals/fasting, dehydration
Hormonal: menses, ovulation
Dietary: alcohol (esp. red wine), aged cheeses (tyramine), processed meats (nitrates), MSG, artificial sweeteners, caffeine
withdrawal or excess
Environmental: bright/flickering lights, strong odors, weather/barometric changes
Medication-related: vasodilators (nitroglycerin), OCPs/hormone shifts
Headache red flags — “SNOOP10” (Table 36-1 style)
Systemic symptoms/illness (fever, weight loss, cancer, HIV)
Neurologic deficits (confusion, focal signs, seizures)
Onset abrupt (“thunderclap”), Older age at onset (>50), Occipital w/ exertion
Pattern change/progressive, Papilledema, Pregnancy/postpartum, Post-trauma
Also: positional HA, precipitated by Valsalva/exertion, immunosuppression, anticoagulation
→ Urgent evaluation (neuroimaging ± LP) if present.
3) Stepwise management
A) Migraine (acute → preventive)
Acute (abortive)
1. Mild–moderate:
o NSAID (ibuprofen, naproxen) or APAP ± antiemetic (metoclopramide, prochlorperazine)
2. Moderate–severe (or NSAID failure):
o Triptan (sumatriptan, rizatriptan, eletriptan, zolmitriptan, etc.)
o Formulations: SC or intranasal if rapid onset needed or N/V prominent (SC sumatriptan fastest)
3. Refractory / contraindication to triptan:
o DHE (± antiemetic), or newer gepants (ubrogepant, rimegepant) or ditan (lasmiditan; caution driving 8–24 h)
Rules: treat early, avoid MOH (limit triptans/ergots ≤9 days/mo, NSAIDs ≤14 days/mo)
Preventive (when to start)
3
Types (how they differ):
Acute pain: sudden, short duration; protective; sympathetic signs (↑HR, ↑BP). Treat cause + short-term analgesia.
Chronic pain (>3 mo): persists beyond healing; biopsychosocial; goals = function/QOL; avoid long-term high-dose opioids.
Nociceptive pain: tissue injury/inflammation.
o Somatic: well-localized, aching (skin, bone, joints).
o Visceral: diffuse, cramping/pressure (organs), may refer.
Neuropathic pain: nerve injury/dysfunction; burning, shooting, tingling, allodynia; responds best to adjuvants (SNRIs,
TCAs, gabapentinoids).
Malignant (cancer) pain: often mixed (nociceptive + neuropathic); prioritize comfort, use WHO ladder more liberally.
Non-pharmacologic approaches (use with meds in all patients):
Education, goal-setting, CBT, mindfulness
Physical therapy, graded exercise, heat/ice
TENS, acupuncture, spinal manipulation
Sleep hygiene; weight loss; ergonomics; pacing; splints/braces
WHO 3-step ladder (with examples)
Step 1 – Mild pain: non-opioids ± adjuvants
APAP, NSAIDs (e.g., ibuprofen, naproxen); topicals (diclofenac gel, lidocaine patch); adjuvants if neuropathic.
Step 2 – Moderate pain: weak/short-acting opioids + Step 1 ± adjuvants
Tramadol or low-dose short-acting opioid (hydrocodone/APAP, oxycodone IR) + NSAID/APAP.
Step 3 – Severe pain: strong opioids + Step 1 ± adjuvants
Morphine, hydromorphone, oxycodone, fentanyl, methadone; consider nerve blocks, spinal analgesia in cancer pain.
Use validated pain scales (NRS 0–10; Figure 35-1) and follow a stepwise algorithm (Figure 35-2; Table 35-1 aligns analgesic
selection with pain intensity).
NSAIDs
MOA: inhibit COX-1/COX-2 → ↓ prostaglandins → ↓ peripheral/central sensitization (analgesic, anti-inflammatory, antipyretic).
Indications: inflammatory nociceptive pain (musculoskeletal, osteoarthritis, sprains, dysmenorrhea).
Precautions/adverse effects:
GI irritation/ulcer/bleed (↑ risk with age, steroids, anticoagulants)
Renal vasoconstriction → AKI, Na⁺/H₂O retention; avoid in advanced CKD
CV risk (MI/stroke), ↑ BP; naproxen may have the most favorable CV profile
Platelets: nonselective NSAIDs inhibit TXA₂ (reversible); ibuprofen can blunt aspirin’s antiplatelet effect (separate dosing)
COX-2 (celecoxib): ↓ GI risk, but caution in CV disease
Is one NSAID safer/better?
Analgesic efficacy is similar at equipotent doses; choose by patient risk: GI (consider PPI or COX-2), CV (avoid
COX-2/high-dose diclofenac), renal (avoid class).
Ceiling effect: yes—once analgesic ceiling reached, higher doses ↑ toxicity without more pain relief (e.g., ibuprofen >400 mg/dose
gives little extra analgesia).
Special: ketorolac max 5 days (GI/renal risk).
Acetaminophen (APAP)
MOA: central prostaglandin (COX) inhibition → analgesic + antipyretic (minimal anti-inflammatory).
Indications: mild pain/fever; OA when NSAIDs risky; combine with other classes for multimodal analgesia.
Dosing/limits:
Typical adult: 325–1,000 mg q4–6h PRN
Absolute max: 4 g/day (all sources)
Many practices cap at 3 g/day (safer)
Older adults, liver disease, chronic alcohol use: keep ≤2 g/day, avoid if active severe hepatic disease.
1
,Precautions: hepatotoxicity (esp. with alcohol/fasting/overdose); check combination products.
Spectrum vs NSAIDs: APAP lacks anti-inflammatory effect; safer GI/renal profile when inflammation isn’t prominent.
Adjuvant analgesics (what & when)
Use when neuropathic features (e.g., DPN, PHN), fibromyalgia, central sensitization, or as opioid-sparing agents.
Antidepressants: SNRIs (duloxetine, venlafaxine), TCAs (nortriptyline, amitriptyline)
Anticonvulsants: gabapentin, pregabalin, carbamazepine (trigeminal neuralgia)
Topicals: lidocaine 5% patch (PHN), capsaicin
Muscle relaxants: tizanidine, baclofen (spasticity)
Others (specialist): ketamine (NMDA antagonist) in refractory pain; clonidine/dexmedetomidine (α2 agonists);
corticosteroids for cancer/bone pain or nerve compression
Opioids
MOA: μ-opioid receptor agonism (± κ/δ) → ↓ neurotransmitter release & postsynaptic excitability in pain pathways (spinal &
supraspinal).
Common adverse effects & management:
Constipation (no tolerance): prophylax with stimulant laxative (senna ± docusate) and fluids/fiber; refractory OIC →
peripherally acting μ-antagonists (PAMORAs: methylnaltrexone, naloxegol, naldemedine)
Nausea/vomiting: usually transient; ondansetron or prochlorperazine
Sedation: dose-reduce, space doses, consider stimulant in palliative settings
Respiratory depression: avoid rapid titration, caution with sedatives; naloxone for overdose
Pruritus: antihistamine or rotate opioid (often histamine-release with morphine)
Endocrine (↓ HPG axis), urinary retention, QT prolongation (methadone), opioid-induced hyperalgesia (consider dose
reduction/rotation)
Tolerance develops to most effects except constipation & miosis.
True opioid allergy (anaphylaxis) – reasonable alternatives:
Opioids fall into 3 main chemical classes—cross-reactivity is more likely within a class:
Phenanthrenes: morphine, codeine, hydromorphone, oxycodone, hydrocodone
Phenylpiperidines: fentanyl, meperidine
Diphenylheptanes: methadone
→ If true IgE to a phenanthrene (e.g., morphine), switch to a phenylpiperidine (fentanyl) or diphenylheptane (methadone)
and monitor.
Equianalgesic dosing, incomplete cross-tolerance, rotation
Equianalgesic dose: a dose of opioid B that provides ~the same analgesia as opioid A.
Incomplete cross-tolerance: when switching opioids, the patient is less tolerant to the new opioid → reduce the calculated
equianalgesic dose by ~25–50% (more reduction for high doses, frail/older adults), then titrate.
Example manual conversion (illustrative):
Patient takes morphine 60 mg PO/day (15 mg q6h).
Oral morphine : oxycodone ≈ 1.5 : 1 (approximate).
o 60 mg morphine/day ≈ 40 mg oxycodone/day.
Apply 30–50% reduction for incomplete cross-tolerance → new target 20–28 mg/day.
o Practical regimen: oxycodone IR 5 mg q6h (20 mg/day) with PRN rescue, reassess in 24–48 h.
(You’d choose different products/intervals to match patient factors and pain pattern.)
Always reassess pain, function, adverse effects, and total daily MME, and document goals/risks.
Quick reference: picking & protecting
Start with non-pharm + APAP/NSAID (if safe).
Add adjuvant if neuropathic features.
Escalate to short-acting opioid for breakthrough severe pain; convert to long-acting only when stable.
Bowel regimen from day 1 with any opioid.
2
, Revisit goals frequently; deprescribe/rotate as needed.
_________________________________________________________________________________________________Headaches
Migraine & Cluster Headaches — What to Know
1) IHS Classification (diagnostic criteria)
Migraine without aura
≥5 attacks lasting 4–72 h (untreated/unsuccessfully treated)
≥2 of: unilateral, pulsating, moderate–severe intensity, aggravated by routine activity
During HA ≥1 of: nausea/vomiting OR photophobia + phonophobia
Not better explained by another diagnosis
Migraine with aura
≥2 attacks with fully reversible aura (visual, sensory, speech/language; ± brainstem, retinal; motor aura may last longer)
≥3 of: gradual spread (≥5 min), ≥2 aura symptoms in succession, each aura 5–60 min (motor up to 72 h), ≥1 unilateral, ≥1
positive (scintillations/tingling), headache during aura or within 60 min after
Cluster headache
Severe/very severe unilateral orbital/supraorbital/temporal pain 15–180 min
Frequency: 1 every other day → 8/day during a cluster period
With ipsilateral autonomic signs (≥1): conjunctival injection/tearing, nasal congestion/rhinorrhea, eyelid edema,
forehead/facial sweating, miosis/ptosis and/or marked restlessness/agitation
2) Headache diary, triggers & red flags
Headache diary
Track date/time, duration, severity, associated symptoms, meds used/response, sleep, stress, menses, foods,
caffeine/alcohol, weather. Helps identify triggers & medication-overuse headache (MOH).
Common migraine triggers (Table 36-2 style)
Lifestyle: stress, let-down after stress, sleep loss or excess, skipped meals/fasting, dehydration
Hormonal: menses, ovulation
Dietary: alcohol (esp. red wine), aged cheeses (tyramine), processed meats (nitrates), MSG, artificial sweeteners, caffeine
withdrawal or excess
Environmental: bright/flickering lights, strong odors, weather/barometric changes
Medication-related: vasodilators (nitroglycerin), OCPs/hormone shifts
Headache red flags — “SNOOP10” (Table 36-1 style)
Systemic symptoms/illness (fever, weight loss, cancer, HIV)
Neurologic deficits (confusion, focal signs, seizures)
Onset abrupt (“thunderclap”), Older age at onset (>50), Occipital w/ exertion
Pattern change/progressive, Papilledema, Pregnancy/postpartum, Post-trauma
Also: positional HA, precipitated by Valsalva/exertion, immunosuppression, anticoagulation
→ Urgent evaluation (neuroimaging ± LP) if present.
3) Stepwise management
A) Migraine (acute → preventive)
Acute (abortive)
1. Mild–moderate:
o NSAID (ibuprofen, naproxen) or APAP ± antiemetic (metoclopramide, prochlorperazine)
2. Moderate–severe (or NSAID failure):
o Triptan (sumatriptan, rizatriptan, eletriptan, zolmitriptan, etc.)
o Formulations: SC or intranasal if rapid onset needed or N/V prominent (SC sumatriptan fastest)
3. Refractory / contraindication to triptan:
o DHE (± antiemetic), or newer gepants (ubrogepant, rimegepant) or ditan (lasmiditan; caution driving 8–24 h)
Rules: treat early, avoid MOH (limit triptans/ergots ≤9 days/mo, NSAIDs ≤14 days/mo)
Preventive (when to start)
3
