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Harrison's Section 1: Pain (Chapter 14)

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Overview

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1. THE PAIN SENSORY SYSTEM

Peripheral Mechanisms

• Aδ and C fibers are called primary afferent nociceptors
• Conduction block of Aδ and C fibers completely abolishes detection of painful stimuli
• Nociceptors respond to: heat, intense cold, intense mechanical distortion, acidic pH, ATP, serotonin, bradykinin, histamine
• TRPV1 (vanilloid receptor) - transient receptor potential cation channel; activated by heat, acid pH, capsaicin, and endogenous mediators

Sensitization

• Products of inflammation: bradykinin, prostaglandins, leukotrienes, serotonin, substance P, histamine, H+ ions, ATP, products of proteolysis
• This creates peripheral sensitization - a lowered threshold and increased responsiveness
• Allodynia: pain in response to a normally non-painful stimulus (e.g., sunburned skin painful to light touch)
• Hyperalgesia: exaggerated pain to a normally painful stimulus

Central Mechanisms

• Aδ and C fibers synapse on neurons in the dorsal horn of the spinal cord
• Glutamate and substance P are the key nociceptive neurotransmitters at these synapses
• Dorsal horn neurons send signals via the spinothalamic tract to the thalamus and cortex

• Repeated C fiber stimulation causes progressive amplification of dorsal horn neuron activity
• Mediated by the NMDA receptor (N-methyl-D-aspartate)
• Wind-up = the progressive increase in dorsal horn neuron firing with repeated stimulation
• Central sensitization contributes to: allodynia, hyperalgesia, and spread of pain beyond the injury site

• Thalamic relay neurons project to somatosensory cortex (location and quality of pain) and limbic structures (emotional component)
• The anterior cingulate cortex is particularly involved in the suffering/emotional aspect of pain

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2. PAIN MODULATION

Endogenous Analgesia Systems

1. PAG → rostral ventromedial medulla (RVM), including the nucleus raphe magnus
2. RVM → dorsal horn via the dorsolateral funiculus
3. Inhibition of dorsal horn nociceptive neurons

• Endorphins, enkephalins, dynorphins - endogenous opioids acting at mu, delta, kappa receptors
• Serotonin (from raphe nuclei)
• Norepinephrine (from locus coeruleus and lateral tegmental noradrenergic neurons)
• Both serotonin and norepinephrine inhibit pain transmission in the dorsal horn - this is the basis for TCA and SNRI analgesia

• Three main types: mu (μ), delta (δ), kappa (κ)
• Most analgesic opioids act primarily at mu receptors
• Located in brain, spinal cord, and peripheral tissues

• Placebo analgesia is real and mediated by endogenous opioids - it is reversible by naloxone
• Expectation, conditioning, and context powerfully modulate pain perception

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3. NEUROPATHIC PAIN

• Ectopic discharge: damaged nerves fire spontaneously without a stimulus
• Sympathetically maintained pain: norepinephrine from sympathetic neurons activates nociceptors (contributes to complex regional pain syndrome - CRPS)
• Central sensitization: abnormal amplification in the dorsal horn and higher centers
• Loss of inhibitory interneurons: reduced GABAergic inhibition in the dorsal horn

• Burning, shooting, electric-shock quality
• Allodynia (pain from light touch)
• Hyperalgesia
• Dysesthesias (unpleasant abnormal sensations)
• Spontaneous pain without ongoing tissue damage

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4. ACUTE PAIN MANAGEMENT

Opioid Analgesics

• Mechanism: act at mu receptors in brain, spinal cord, and periphery
• Supraspinal sites: PAG, RVM (activates descending inhibition)
• Spinal sites: direct inhibition of dorsal horn nociceptive neurons
• Peripheral sites: activated in inflamed tissue

• Opioids are the most effective analgesics for moderate-to-severe acute pain
• Tolerance (need higher dose for same effect) and physical dependence (withdrawal on abrupt cessation) are predictable physiologic phenomena - different from addiction
• Addiction = compulsive use despite harm - rare when opioids used appropriately for pain

• Morphine - gold standard
• Hydromorphone - more potent, useful in renal failure
• Oxycodone - oral
• Fentanyl - high potency, rapid onset, used IV/transdermal
• Meperidine (pethidine) - avoid for chronic use (normeperidine accumulation causes CNS excitation, seizures)

• Constipation (no tolerance develops - always treat prophylactically)
• Nausea/vomiting
• Sedation, respiratory depression (serious - monitor in opioid-naive)
• Pruritus (especially neuraxial opioids)
• Urinary retention
• Tolerance and physical dependence

NSAIDs and Acetaminophen

• NSAIDs block prostaglandin synthesis (COX inhibition), reducing peripheral sensitization
• Most effective for pain with an inflammatory component
• GI toxicity (COX-1 inhibition) - use PPI prophylaxis
• Selective COX-2 inhibitors (celecoxib): less GI toxicity but cardiovascular risk
• Acetaminophen: effective analgesic/antipyretic; mechanism not fully understood; hepatotoxic in overdose

Adjuvants for Acute Pain

• Ketamine (NMDA antagonist): low-dose IV reduces opioid requirements post-op
• Glucocorticoids: reduce inflammatory pain; also act centrally
• Alpha-2 agonists (clonidine, dexmedetomidine): supraspinal and spinal analgesia

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5. CHRONIC PAIN

Definition and Concepts

• Pain persisting beyond normal tissue healing time (conventionally >3 months)
• Biopsychosocial model is essential: biological, psychological, and social factors all contribute
• "Pain behaviors": learned behaviors that persist even after healing
• Emotional distress and depression commonly co-exist and amplify pain perception
• Catastrophizing (fear, helplessness about pain) strongly predicts disability

Assessment

1. Identify any treatable underlying cause
2. Set realistic, functional treatment goals (e.g., sleep better, return to work)
3. Quantify impact on function, mood, sleep, and social relationships
4. Screen for psychological comorbidities (depression, anxiety, PTSD, substance use)

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6. TREATMENT OF CHRONIC PAIN

A. Antidepressant Medications

• Best choices: nortriptyline and desipramine (better side effect profiles than amitriptyline)
• Analgesia occurs at lower doses and faster than antidepressant effect
• Effective even in non-depressed patients
• Mechanism: block reuptake of serotonin and norepinephrine → enhance descending inhibition
• May potentiate opioid analgesia - useful add-on for cancer pain

• Postherpetic neuralgia
• Diabetic neuropathy
• Fibromyalgia
• Tension headache
• Migraine headache
• Rheumatoid arthritis (benefit but not direct analgesia in controlled studies)
• Chronic low back pain
• Cancer pain
• Central poststroke pain

• Orthostatic hypotension
• Drowsiness
• Cardiac conduction delay
• Memory impairment
• Constipation
• Urinary retention

• Similar mechanism to TCAs but fewer side effects
• Duloxetine FDA-approved for diabetic peripheral neuropathy, fibromyalgia, chronic musculoskeletal pain
• Generally preferred over TCAs in older patients

• Weaker analgesic effect than TCAs or SNRIs
• Useful primarily if depression is the main driver

B. Anticonvulsants / Membrane-Stabilizing Drugs (Table 14-3 region)

• Gabapentin and pregabalin - bind to α2δ subunit of voltage-gated calcium channels
• Reduce calcium-dependent neurotransmitter release from nociceptive neurons
• First-line for: postherpetic neuralgia, diabetic neuropathy, fibromyalgia (pregabalin)
• Side effects: sedation, dizziness, peripheral edema, weight gain

• First-line for trigeminal neuralgia - blocks sodium channels
• Also used in other lancinating neuropathic pains
• Requires monitoring: CBC, LFTs; risk of aplastic anemia, Stevens-Johnson syndrome (especially in Han Chinese - HLA-B*1502 testing)

C. Opioids in Chronic Non-Cancer Pain

• Use opioids only when benefits outweigh risks; try non-opioid therapies first
• Start low, go slow
• Prescribe the lowest effective dose
• Avoid concurrent benzodiazepines if possible (greatly increases overdose risk)
• Use urine drug testing before and during therapy
• Check prescription drug monitoring programs (PDMPs)
• Use written opioid treatment agreements
• Reassess regularly; taper if risks outweigh benefits
• For patients on ≥50 MME/day - consider risk-benefit; ≥90 MME/day should be carefully justified
• Prescribe naloxone to high-risk patients
• Screen for opioid use disorder (OUD) - if present, offer medication-assisted treatment (buprenorphine, methadone)

• Personal or family history of substance use disorder
• Young age
• Depression, anxiety, PTSD
• History of sexual abuse

D. Interventional Procedures

• Epidural glucocorticoid injections: acute radicular pain (e.g., disc herniation)
• Radiofrequency ablation of facet joints: chronic facet-related neck/back pain
• Nerve blocks: diagnostic and therapeutic
• Spinal cord stimulation (SCS): electrodes placed in epidural space over dorsal columns; significant benefit in refractory pain; used for failed back surgery syndrome, CRPS
• Peripheral nerve stimulation
• All invasive procedures should be preceded by multidisciplinary pain clinic evaluation

E. Non-Pharmacologic Approaches

• Physical therapy: essential; improves function, reduces fear-avoidance
• Cognitive-behavioral therapy (CBT): most evidence-based psychological treatment for chronic pain; addresses catastrophizing, pain behaviors, activity avoidance
• Multidisciplinary pain programs: combine medical, psychological, physical rehabilitation
• Mindfulness-based stress reduction (MBSR)
• Acupuncture: modest evidence for some conditions

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7. TREATMENT OF NEUROPATHIC PAIN (Summary Algorithm)

1. TCAs (nortriptyline/desipramine) or SNRIs (duloxetine/venlafaxine)
2. Gabapentin or pregabalin
3. Topical lidocaine patch (for postherpetic neuralgia, localized pain)
4. Topical capsaicin (high-concentration patch - 8%)

• Opioids (tramadol first, then stronger opioids)
• Combination therapy

• Trigeminal neuralgia → carbamazepine first-line
• CRPS → early mobilization, sympathetic nerve blocks, SCS

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8. KEY TABLES

Table 14-1: Anticonvulsant and TCA Drugs for Neuropathic Pain

Table 14-2: Painful Conditions Responding to Tricyclics

Table 14-3: CDC Guidelines for Chronic Opioid Therapy

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9. CORE CONCEPTS TO REMEMBER

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Harrison's Section 1 Pain - Chapters 15-19 (22nd Ed, 2025)

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CHAPTER 15: Chest Discomfort

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Epidemiology

• One of the top 3 reasons for ED visits in the USA - 6-7 million visits/year

• 60% of patients are hospitalized for further testing

• <15% are ultimately diagnosed with Acute Coronary Syndrome (ACS)
• Most common diagnoses: gastrointestinal causes > musculoskeletal > cardiac
• The challenge: identifying the dangerous minority among a large benign majority

Initial Diagnostic Framework - 3 Categories

Causes of Chest Discomfort

Myocardial Ischemia

• Caused by mismatch between myocardial oxygen supply and demand
• Quality: pressure, squeezing, heavy, burning - described as weight on chest
• Location: substernal, may radiate to left arm, jaw, neck, back, right arm
• Not typically sharp or pleuritic
• Typically lasts 2-10 min (stable angina) or >20 min (ACS)
• Precipitants: exertion, cold, emotional stress
• Unstable angina: new-onset, increasing frequency/severity, or rest pain

Aortic Dissection

• Tearing or ripping quality - worst pain of life, sudden onset
• Maximal from onset (unlike MI which builds)
• May radiate to back (inter-scapular = descending aorta)
• Associated with hypertension, Marfan syndrome, bicuspid aortic valve, pregnancy
• Pulse differential between arms; wide mediastinum on CXR

Pulmonary Embolism (PE)

• Pleuritic chest pain + dyspnea + tachycardia
• Risk factors: DVT, immobility, malignancy, recent surgery, OCP
• Massive PE: hemodynamic collapse, right heart strain (S1Q3T3 on ECG, RV dilation)

Pericarditis

• Sharp, pleuritic pain - worse lying flat, relieved leaning forward
• Friction rub on auscultation
• Diffuse ST elevation, PR depression on ECG
• Treat: NSAIDs + colchicine

Pneumothorax

• Sudden pleuritic pain + dyspnea, decreased breath sounds
• Spontaneous (tall, young men; Marfan) or tension (hemodynamic emergency)

Gastrointestinal Causes (most common overall)

• GERD: burning substernal - worse postprandial/lying down, relieved by antacids
• Esophageal spasm: can mimic angina; responds to nitrates (don't confuse!)
• Peptic ulcer: epigastric, food-related pattern

Musculoskeletal

• Costochondritis: point tenderness over costochondral junctions - reproduced by pressing
• Tietze syndrome: swelling + tenderness over cartilage
• Chest wall injury, rib fracture

Others

• Anxiety/Panic: atypical features, associated with hyperventilation, palpitations
• Herpes zoster: dermatomal burning pain, precedes rash

Evaluation of Chest Discomfort

History - Key Questions

1. Quality: pressure vs pleuritic vs burning vs tearing
2. Location + radiation
3. Onset: sudden (dissection, PE, pneumothorax) vs gradual (ischemia, GERD)
4. Duration and time course
5. Aggravating/relieving: exertion (ischemia), breathing (pleuritic), position (pericarditis, GERD), food (GERD, peptic)
6. Associated symptoms: dyspnea, diaphoresis, nausea (ischemia), syncope (massive PE/aortic)

TIMI Risk Score (for ACS risk stratification)

Physical Examination

• Vital signs: BP (both arms if dissection suspected), HR, SpO2
• Cardiac: S3/S4, murmurs (aortic regurgitation in dissection)
• Lungs: decreased BS (pneumothorax/effusion), crackles (pulmonary edema)
• Chest wall: tenderness (MSK)

Key Investigations

HEART Score (for ED chest pain)

• History, ECG, Age, Risk factors, Troponin
• Score 0-3: low risk (0.9-1.7% MACE) - safe discharge
• Score 4-6: moderate risk - observe/admit
• Score 7-10: high risk (50-65% MACE) - urgent cardiology

Chest Radiography Findings

• Normal does not exclude serious disease (aortic dissection, PE, ACS)
• Widened mediastinum (>8 cm): aortic dissection
• Pleural effusion + cardiomegaly: heart failure
• Unilateral opacification: pneumonia, effusion
• Loss of lung markings + tracheal deviation: tension pneumothorax

Outpatient Evaluation

• Low-risk patients: negative troponins x2, normal ECG, low clinical probability
• Consider stress testing or coronary CTA before discharge
• TIMI 0 + normal ECG + neg serial troponins = safe for outpatient work-up

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CHAPTER 16: Abdominal Pain

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Overview

Mechanisms of Abdominal Pain

1. Inflammation of Parietal Peritoneum

• Steady, aching pain, well-localized (somatic nerves)
• Intensity depends on: type of material (acidic gastric juice > feces > blood/urine), amount, rate of contact
• Sterile acidic gastric juice > grossly contaminated neutral pH feces (for pain intensity)
• Enzymatically active pancreatic juice > sterile bile
• Blood and urine are mild irritants - may go unnoticed unless sudden/massive
• Accentuated by movement - patient lies still (vs colic patient who writhes)
• Rebound tenderness and abdominal rigidity (tonic muscle spasm)
• Muscle spasm may be minimal with: retrocecal appendix, lesser sac perforation, obtunded/immunosuppressed patients, slowly developing processes

2. Obstruction of Hollow Viscera

• Colicky, intermittent pain - poorly localized
• Small bowel obstruction: periumbilical/supraumbilical, intermittent; radiation to lumbar region if mesenteric traction
• Colonic obstruction: infraumbilical, less intense, radiates to lumbar
• Biliary obstruction: "biliary colic" is a misnomer - actually steady pain (not colicky); right upper quadrant ± right shoulder radiation
• Ureteral obstruction: severe flank/loin pain radiating to groin - renal colic

3. Vascular Disturbances

• Mesenteric ischemia: severe pain out of proportion to findings - "periumbilical pain after eating" (intestinal angina); risk factors: atrial fibrillation, atherosclerosis, hypercoagulable state
• Pain typically precedes peritoneal signs

4. Referred Pain

5. Abdominal Wall Pain

• Cutaneous nerve entrapment or muscle strain
• Carnett's test: pain worsens when abdominal muscles contracted (distinguish from visceral)

Medical Causes of Abdominal Pain (No Surgery Needed)

• Metabolic: DKA (pain from ketones), Addisonian crisis, porphyria, hyperlipidemia
• Hematologic: sickle cell crisis, Henoch-Schönlein purpura
• Toxins: lead poisoning, black widow spider bite
• Infections: herpes zoster (before rash), pneumonia (lower lobe - refers to abdomen), pharyngitis (in children)
• Neurologic: nerve root compression
• Drugs: narcotic withdrawal, corticosteroids

Clinical Assessment of Abdominal Pain

History

1. Onset: sudden (perforation, vascular catastrophe, renal colic) vs gradual (inflammatory)
2. Character: colicky (obstruction), steady/aching (peritonitis, solid organ)
3. Location and migration (appendicitis: periumbilical → RIF)
4. Radiation (pancreatitis → back; gallbladder → right shoulder)
5. Associated: nausea/vomiting (obstruction, appendicitis), diarrhea (gastroenteritis, colitis), fever (infection/inflammation), hematuria (renal colic), jaundice (biliary), vaginal bleeding (ectopic pregnancy)
6. Menstrual history - always ask in women of childbearing age (ectopic, PID, ovarian torsion)
7. Last bowel movement - obstruction/constipation
8. Aggravating: movement (peritonitis), food (ischemia, peptic)

Physical Examination

• Observe patient: lies still (peritonitis) vs writhing (colic)
• Vital signs: fever, hypotension/tachycardia (sepsis, hemorrhage)
• Inspection: distension, peristaltic waves (obstruction), hernia orifices
• Auscultation: high-pitched tinkling (obstruction), absent bowel sounds (ileus/perforation)
• Palpation: tenderness, guarding, rigidity, rebound
• Special signs:
  • Murphy's sign: inspiratory arrest on RUQ palpation (acute cholecystitis)
  • McBurney's point: 2/3 from umbilicus to right ASIS (appendicitis)
  • Rovsing's sign: RIF pain on LIF palpation (appendicitis)
  • Psoas sign: pain with hip extension (retrocecal appendicitis)
  • Obturator sign: pain with internal hip rotation (pelvic appendicitis, pelvic abscess)
  • Cullen's sign: periumbilical bruising (retroperitoneal hemorrhage - pancreatitis, ruptured ectopic)
  • Grey Turner's sign: flank bruising (same as above)

Investigations

• Bloods: FBC (leukocytosis), CRP, amylase/lipase (pancreatitis), LFTs (biliary), lactate (ischemia), urine hCG (ectopic)
• Urinalysis: hematuria (renal colic, UTI), WBCs (UTI/pyelonephritis)
• Plain AXR: dilated loops (obstruction), free gas under diaphragm (perforation - but erect CXR better), calcified gallstones/renal stones
• USS abdomen: gallstones, biliary dilation, appendicitis (children), ovarian pathology, aortic aneurysm
• CT abdomen/pelvis: most useful for acute abdomen - appendicitis, diverticulitis, pancreatitis, obstruction, ischemia, perforation

Key Diagnostic Pitfalls

• Elderly and immunosuppressed: minimal signs despite serious disease
• Early appendicitis: no peritonism, normal WCC possible
• Ectopic pregnancy: always check hCG in women of childbearing age
• Mesenteric ischemia: "pain out of proportion to signs"

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CHAPTER 17: Headache

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Classification (IHS - International Headache Society)

Anatomy and Physiology of Headache

• Scalp, meningeal arteries, dural sinuses, falx cerebri, proximal pial arteries
• NOT pain-sensitive: ventricular ependyma, choroid plexus, pial veins, brain parenchyma

1. Trigeminal nerve innervates large intracranial vessels and dura mater
2. Pain signals → trigeminal nucleus caudalis (extends to C1-C2 dorsal horns = trigeminocervical complex)
3. Relayed to ventroposteromedial thalamus → cortex
4. Modulated by hypothalamus and brainstem (PAG, raphe nuclei)

Evaluation of Acute New-Onset Headache

RED FLAGS ("SNOOP4" mnemonic)

• Systemic symptoms (fever, weight loss)
• Neurologic deficits (focal symptoms, altered consciousness)
• Onset sudden/thunderclap (worst headache of life - subarachnoid until proven otherwise)
• Older age (>50) - new headache (GCA, mass)
• Papilledema
• Postural component (orthostatic - low CSF pressure; worse lying flat - raised ICP)
• Previous history of cancer / HIV / immunosuppression
• Precipitated by exertion / Valsalva (SAH, posterior fossa lesion)

Thunderclap Headache

• Sudden, severe, maximal at onset ("hit over the head")
• Must rule out subarachnoid hemorrhage (SAH): LP (xanthochromia) if CT negative
• Other causes: cerebral venous thrombosis, reversible cerebral vasoconstriction syndrome (RCVS), hypertensive urgency

Secondary Headache Causes

Primary Headache Disorders

Migraine

• ≥5 attacks lasting 4-72 hours
• At least 2 of: unilateral, pulsating, moderate/severe intensity, worsened by activity
• At least 1 of: nausea/vomiting, photophobia + phonophobia

• Fully reversible neurologic symptoms (visual most common - scintillating scotoma, fortification spectra; sensory, language, motor)
• Aura lasts 20-60 minutes, typically precedes headache

• Cortical spreading depression (CSD): wave of neuronal depolarization sweeping across cortex at 3-5 mm/min - underlies aura
• Activates the trigeminovascular system → CGRP release → sterile meningeal inflammation
• CGRP (calcitonin gene-related peptide): key mediator - dilates meningeal vessels, transmits pain signals; basis for new drug targets (gepants, CGRP monoclonal antibodies)
• Hypothalamic activation is the source of premonitory phase (yawning, food cravings)

1. Premonitory (hours-days before): mood changes, yawning, neck stiffness, food cravings
2. Aura (if present): 20-60 min visual/sensory/motor symptoms
3. Headache: 4-72 hrs, typically unilateral pulsating + nausea/photo/phonophobia
4. Postdrome: fatigue, cognitive fog

• Mild-moderate: NSAIDs (ibuprofen, naproxen), paracetamol, aspirin ± antiemetic
• Moderate-severe: Triptans (5-HT1B/1D agonists) - sumatriptan, rizatriptan, eletriptan; most effective when taken early
• Newer: Gepants (CGRP receptor antagonists) - ubrogepant, rimegepant; useful if triptans contraindicated (cardiac disease)
• Ditans (5-HT1F agonists) - lasmiditan; no vasoconstriction, can use in vascular disease
• Anti-emetics: metoclopramide, prochlorperazine (also analgesic)
• Avoid opioids - risk of medication overuse headache

• Beta-blockers: propranolol, metoprolol (first-line)
• Tricyclics: amitriptyline
• Anticonvulsants: valproate, topiramate
• CGRP monoclonal antibodies: erenumab, fremanezumab, galcanezumab (monthly/quarterly injections); highly effective, well-tolerated, revolutionized prophylaxis
• Flunarizine (calcium channel blocker - not available in USA)
• Botulinum toxin A (Botox): approved for chronic migraine (≥15 days/month)

Tension-Type Headache (TTH) - Most Common Headache (69%)

• Bilateral, pressing/tightening (non-pulsating) quality
• Mild-moderate intensity (does NOT prohibit activity)
• No nausea/vomiting (nausea rare in chronic TTH)
• No more than one of photophobia or phonophobia

• Acute: NSAIDs, paracetamol, aspirin
• Preventive (chronic TTH): amitriptyline (best evidence)

Cluster Headache

• Unilateral, periorbital/retro-orbital, excruciating (patient is agitated - opposite of migraine patient)
• Duration: 15-180 minutes
• Frequency: 1-8 attacks per day
• Autonomic features (ipsilateral): lacrimation, conjunctival injection, rhinorrhea, nasal congestion, ptosis, miosis, periorbital edema, facial flushing
• Clustering pattern: attacks occur daily for weeks-months, then remission

• 100% O2 by non-rebreather mask (12-15 L/min x 15 min) - very effective
• Subcutaneous sumatriptan 6 mg - fastest-acting triptan
• Intranasal sumatriptan or zolmitriptan

• Verapamil (first-line) - calcium channel blocker
• Short-term: prednisolone (break a cluster period quickly)
• Lithium (chronic cluster)
• Methysergide

Trigeminal Autonomic Cephalalgias (TACs)

Chronic Daily Headache (CDH)

• Headache on ≥15 days/month for >3 months
• Most common cause: transformed migraine (episodic migraine → CDH)
• Major risk factor: medication overuse headache (MOH)

Medication Overuse Headache (MOH)

• Analgesic use on ≥10-15 days/month causes paradoxical rebound headache
• Triptans/ergots/opioids: >10 days/month
• NSAIDs/paracetamol: >15 days/month
• Treatment: withdraw the overused medication (supervised withdrawal - headache initially worsens)
• Prevention: educate patients when first prescribing acute treatments

New Daily Persistent Headache (NDPH)

• Headache that becomes daily from day 1 and never stops
• Must exclude secondary causes (especially CSF pressure disorders)
• Often refractory

Primary Care and Headache Management

1. Distinguish primary from secondary (red flags)
2. Diagnose the specific primary headache type
3. Educate: keep headache diary, identify triggers
4. Stratify: mild (step care) vs moderate-severe (stratified care - triptan first-line)
5. Preventive treatment if attack frequency/disability warrants
6. Address MOH proactively
7. Multidisciplinary approach for refractory cases

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CHAPTER 18: Low Back Pain

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Epidemiology

• Leading cause of disability worldwide and principal cause of work-related disability in industrialized countries
• 28-34% of Americans had LBP in the past 3 months

• 57 million unique patient visits/year

• Estimated all-cause medical costs: >$300 billion/year in USA
• Risk factors for chronic LBP: female sex, African-American race, older age, unemployment, obesity, sedentary lifestyle

Pain Categorization (Table 18-1)

1. Nociceptive Pain

• Most common - from actual/potential tissue damage
• Worsens with activities that stress the causative structure
• Usually from degenerative changes; tends to be progressive
• Mechanical pain can radiate to upper/lower leg but in variable, non-dermatomal patterns
• More proximal than radicular pain

2. Neuropathic Pain

• From injury/disease of somatosensory nervous system
• Accompanied by paresthesias, numbness, allodynia
• More unpredictable with wide fluctuations and paroxysms
• Focal neurologic findings (loss of sensorimotor function or reflexes)
• Important: radiculopathy can occur WITHOUT pain; radicular pain can occur WITHOUT neurologic deficits

3. Nociplastic Pain (newest category)

• Pain from abnormal processing without tissue damage or somatosensory pathology (central sensitization)
• = "Nonspecific LBP"
• Features: diffuse pain, superficial tenderness, pain patterns deviating from neuroanatomy
• Pain-induced weakness, multiple simultaneous pain conditions, sensory deficits outside dermatomal maps
• ~10-20% of the back pain population

Causes of Low Back Pain

Localized Structures

• Muscle/ligament strain: most common acute LBP; improves in <6 weeks in most
• Disc herniation: nucleus pulposus protrudes → nerve root compression → radiculopathy; L4-L5 (L5 root) and L5-S1 (S1 root) most common
• Spinal stenosis: narrowing of spinal canal → neurogenic claudication (pain/weakness with walking, relieved by sitting/leaning forward); bilateral in older patients
• Degenerative disc/facet disease: most common cause of chronic LBP
• Spondylolisthesis: forward slip of one vertebra on another; L4-L5 most common
• Spondylolysis: defect in pars interarticularis; young athletes (gymnasts, fast bowlers)
• Osteoporotic vertebral fracture: in elderly women - acute severe pain after minimal trauma
• Sacroiliitis: inflammatory - ankylosing spondylitis, psoriatic arthritis

Red Flag Causes (must not miss)

• Malignancy: back pain at rest/night, history of cancer, unintentional weight loss, older age, no improvement with conservative therapy
• Infection (discitis/osteomyelitis/epidural abscess): fever, IV drug use, immunosuppression, recent spinal procedure; can rapidly cause permanent neurologic damage
• Cauda equina syndrome: saddle anaesthesia, bladder/bowel dysfunction (urinary retention most sensitive), bilateral leg weakness - surgical emergency
• Abdominal aortic aneurysm: pulsatile abdominal mass, back pain, vascular risk factors - do not palpate vigorously

Red Flags for Low Back Pain

Lumbar Radiculopathy - Root Signs

Investigations

• Most patients do NOT need immediate imaging
• Imaging indications: red flags, neurologic deficits, failure of conservative treatment after 6 weeks
• MRI (gold standard): best for soft tissue (disc, nerve roots, spinal cord, infections, tumors)
• CT scan: better for bony detail (fractures, spinal stenosis)
• Plain X-ray: fractures, alignment (spondylolisthesis), infection screening, ankylosing spondylitis (bamboo spine, sacroiliitis)
• Bone scan: infection, malignancy when MRI unavailable
• EMG/NCS: confirms neuropathic pain, assesses severity, chronicity

Treatment of Low Back Pain

Acute LBP (< 6 weeks) - 90% resolve spontaneously

• Reassurance and activity modification (avoid bed rest - harmful)
• Targeted physiotherapy, core strengthening, education
• Heat (better than cold), massage
• Maintain as much normal activity as possible

• NSAIDs (first-line for acute)
• Non-benzodiazepine muscle relaxants (e.g., cyclobenzaprine, tizanidine)
• Acetaminophen - no longer recommended as first-line (unlikely to provide significant analgesia for back pain)
• Opioids: short course only for debilitating acute pain; avoid long-term; avoid with benzodiazepines
• Gabapentinoids: insufficient evidence for axial or radicular back pain

Chronic LBP (> 3 months)

1. Non-pharmacologic: physiotherapy, exercise (core strengthening), CBT, heat, massage, mindfulness
2. NSAIDs, duloxetine (SNRI - approved for musculoskeletal pain), TCAs
3. Interventional: epidural steroid injections, facet joint injections/radiofrequency ablation
4. Surgery: only after failure of conservative treatment AND clear structural cause with corresponding symptoms

Psychological Therapies

• Depression: 33-67%
• Anxiety: 10-30%
• Substance misuse: 13-40%
• Axis II disorders: >50% in some studies

Surgical Indications

• Cauda equina syndrome: emergency
• Progressive neurologic deficit
• Radiculopathy with clear structural cause not responding to conservative treatment (6-12 weeks)
• Spinal stenosis with severe functional limitation
• Surgery does NOT outperform intensive conservative treatment for most cases of chronic LBP without clear structural cause

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CHAPTER 19: Neck Pain

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Epidemiology

• 4th leading cause of disability in the USA
• Lifetime prevalence: nearly 50%
• Women > men; incidence peaks in late middle life
• Associated with: sport/work injuries, low job satisfaction
• Risk factors: genetics, headache, sleep disorders, smoking, obesity, sedentary lifestyle, secondary gain, trauma, poor physical/mental health

Anatomy

• 50% of cervical motion (flexion, extension, rotation) originates from C1-C2 (atlantoaxial joint)
• 50% from subaxial (C3-C7)
• Any motion restriction requires investigation for underlying pathology

Approach to the Patient

History

• Occupation, past medical history, cancer/fever/weight loss (red flags)
• Pain quality: dull, sharp, electric, stabbing, spasms
• Aggravating/alleviating factors
• Radiation: into occiput, arms, or hands → raises concern for radiculopathy
• Ask specifically about:
  • Numbness/tingling in extremities
  • Clumsiness of hands, change in handwriting, difficulty with buttons → myelopathy
  • Unsteady gait, saddle paresis, bladder/bowel incontinence → spinal cord compression

Examination

• Observe: deformity, mass, skin changes, trauma
• Range of motion: restriction or guarding
• Neurologic examination: upper + lower limb power, sensation, reflexes
• Lhermitte's sign: electric shock down spine on neck flexion → cervical myelopathy
• Spurling's test: lateral neck flexion + axial compression → reproduces radicular arm pain → cervical radiculopathy

Cervical Radiculopathy - Root Signs

Causes of Neck Pain

1. Whiplash (Cervical Strain)

• Acceleration-deceleration injury (most common: rear-end MVA)
• Structures injured: facet joints, muscles, ligaments, discs
• Symptoms: neck pain, stiffness, headache (occipital), shoulder pain
• Most resolve in weeks-months; ~10% develop chronic pain
• Prognostic factors for chronicity: high initial pain intensity, psychological distress, litigation

2. Cervical Spondylosis (Degenerative Disc/Facet Disease)

• Most common cause of neck pain in adults >40 years
• Progressive disc degeneration → osteophyte formation → foraminal/canal narrowing
• Can cause:
  • Axial neck pain (facet and disc pain)
  • Cervical radiculopathy (foraminal compression)
  • Cervical myelopathy (central canal compression) - most serious

3. Cervical Disc Herniation

• Acute: often after trauma or sudden movement
• Lateral herniation → radiculopathy (arm pain, weakness, sensory loss)
• Central herniation → myelopathy (bilateral arm/leg symptoms, gait disturbance)

4. Cervical Myelopathy

• From cervical spinal cord compression (spondylosis most common cause)
• Symptoms: hand clumsiness, gait imbalance, sensory changes, eventually bladder/bowel
• Signs: upper motor neuron signs below level (spasticity, hyperreflexia, upgoing plantars), lower motor neuron signs at level
• Lhermitte's sign positive
• Urgent MRI required - surgical decompression before irreversible damage

5. Inflammatory/Infectious

• Rheumatoid arthritis: C1-C2 instability (atlantoaxial subluxation) - life-threatening; check pre-op; odontoid erosion
• Ankylosing spondylitis: neck stiffness, fusion of vertebrae
• Meningitis: neck stiffness (meningism), fever, headache
• Cervical epidural abscess: fever, rapidly progressive radiculopathy/myelopathy; MRI + urgent drainage

6. Malignancy

• Metastases to cervical spine: breast, lung, prostate, thyroid, renal
• Primary: multiple myeloma, chordoma
• Night pain, unrelenting, history of cancer, weight loss

7. Torticollis

• Acute torticollis (wry neck): sudden onset, often on waking; muscle spasm; usually self-limiting
• Atlantoaxial rotatory subluxation (especially children post-infection): Grisel syndrome
• Spasmodic torticollis (cervical dystonia): involuntary, repetitive muscle contractions; treat with botulinum toxin

8. Other Causes

• Thoracic outlet syndrome: brachial plexus/vascular compression by scalene muscles/1st rib
• Pancoast tumor (apical lung tumor): invades brachial plexus → Horner's syndrome (ptosis, miosis, anhidrosis) + arm pain; check CXR/CT apex
• Posterior fossa/Arnold-Chiari malformation: neck pain + cerebellar signs
• Carotid/vertebral artery dissection: neck pain + Horner's + stroke symptoms → MRI/MRA

Red Flags for Neck Pain

Investigations

• Plain X-ray (AP, lateral, odontoid peg view): fracture, alignment, disc space narrowing, atlantoaxial instability in RA
• MRI: best for discs, nerves, cord, infections, tumors - gold standard
• CT scan: fractures, bony detail
• CT/MR angiography: carotid/vertebral dissection
• EMG/NCS: confirms radiculopathy, assesses severity

Treatment

Conservative (most neck pain resolves in 6 weeks)

• Physiotherapy: mobilization, manipulation (not if myelopathy/instability)
• NSAIDs, muscle relaxants
• Soft collar: short-term only (prolonged use causes deconditioning)
• Cervical traction: for radiculopathy
• Heat, massage

Interventional

• Cervical epidural steroid injection: for radiculopathy
• Facet joint injection/medial branch block
• Radiofrequency ablation of facet joints

Surgical Indications

• Cervical myelopathy: anterior cervical discectomy and fusion (ACDF) or laminoplasty
• Radiculopathy not responding to conservative treatment (6-12 weeks)
• Fracture/instability
• Epidural abscess: urgent surgical drainage

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Summary Comparison Table

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