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Pain Management Series

Overview

Pain management is one of the most common—and most difficult—challenges in medicine.

Effective treatment requires understanding:

Pain physiology
Pain pathophysiology
Mechanistic classification
Acute vs chronic transitions
Pain syndromes
Pharmacologic targets
Patient-specific risk factors

This series is organized in a structured framework:

Physiology → Classification → Time Course → Syndromes → Drug Classes → Special Populations → Clinical Application

I. Pain Physiology & Pathophysiology

Pain Physiology

See: Pain Physiology

Nociceptors
A-delta vs C fibers
Peripheral transduction
Dorsal horn processing
Substance P
NMDA receptors
Ascending pathways
Descending inhibitory pathways

Pain Pathophysiology

See: Pain Pathophysiology

Peripheral sensitization
Central sensitization
Wind-up phenomenon
Neuroimmune activation
Reduced descending inhibition

II. Types of Pain

Nociceptive Pain

See: Nociceptive Pain

Somatic
Visceral
Inflammatory mediators

Neuropathic Pain

See: Neuropathic Pain

Nerve injury or disease
Ectopic firing
Sodium channel dysfunction

Nociplastic Pain

See: Nociplastic Pain

Central sensitization
Altered nociception
Amplified pain processing

Mixed Pain States

See: Mixed Pain States

Combination of mechanisms
Common in chronic pain

III. Acute vs Chronic Pain

Acute Pain

See: Acute Pain

Protective
Tissue injury driven
Short duration

Chronic Pain

See: Chronic Pain

Persistent beyond normal healing
Nervous system remodeling
Central amplification
Psychosocial interaction

IV. Pain Syndromes

Musculoskeletal Syndromes

Musculoskeletal Pain

Neuropathic Syndromes

Neuropathic Pain Syndromes

Centralized Pain Syndromes

Visceral Pain Syndromes

V. Pharmacologic Drug Classes

Pain pharmacotherapy must match mechanism.

This series will cover the following drug classes:

NSAIDs (Most Anti-Inflammatory → Least)

Drug	Primary Pain Type(s)	Acute vs Chronic	Best Clinical Use	Key Pearls / Major Cautions
Indomethacin	Nociceptive, inflammatory	Acute	Acute gout	Strong anti-inflammatory; higher CNS/GI adverse effects
Diclofenac	Nociceptive, inflammatory	Acute + Chronic	OA (esp topical)	Higher CV risk; topical less systemic exposure
Naproxen	Nociceptive, inflammatory	Acute + Chronic	OA, tendinitis	Longer duration; GI/renal risk
Ibuprofen	Nociceptive (somatic), inflammatory	Acute + Chronic	MSK pain, OA flares	GI/renal risk; ↑BP; ceiling effect
Celecoxib	Nociceptive, inflammatory	Acute + Chronic	OA/RA, GI-risk patients	COX-2 selective → less GI ulcer risk; still CV/renal risk

Acetaminophen

Drug	Primary Pain Type(s)	Acute vs Chronic	Best Clinical Use	Key Pearls / Major Cautions
Acetaminophen	Nociceptive (mild)	Acute + Chronic	Baseline analgesic, combination therapy	Liver toxicity risk; ceiling effect; safer in CKD than NSAIDs

Corticosteroids (Anti-Inflammatory Strength Similar; Ordered by Clinical Potency)

Drug	Primary Pain Type(s)	Acute vs Chronic	Best Clinical Use	Key Pearls / Major Cautions
Dexamethasone	Inflammatory, cancer-related edema	Acute	Severe inflammation/edema	Most potent per mg; long acting; hyperglycemia, insomnia
Methylprednisolone	Inflammatory	Acute	Dose packs/flares	Intermediate potency
Prednisone	Inflammatory pain	Acute (bursts)	Radiculitis flares	Not analgesic; treat inflammation; hyperglycemia, mood, BP

Voltage-Gated Sodium Channel Antagonists

Drug	Primary Pain Type(s)	Acute vs Chronic	Best Clinical Use	Key Pearls / Major Cautions
Suzetrigine	Nociceptive (acute), mixed	Acute	Oral peripheral analgesia (Nav1.8)	Emerging agent; selective peripheral action
Lidocaine	Neuropathic (localized), procedural	Acute + Chronic	Topical neuropathic pain; procedures	Helpful in PHN; systemic toxicity if misused

Antiepileptics (Neuropathic Pain Efficacy Strength)

Drug	Primary Pain Type(s)	Acute vs Chronic	Best Clinical Use	Key Pearls / Major Cautions
Carbamazepine	Neuropathic (paroxysmal)	Chronic	Trigeminal neuralgia	Gold standard TN; hyponatremia; CBC/LFT monitoring
Pregabalin	Neuropathic, nociplastic	Chronic	DPN, fibromyalgia	Strong evidence; edema; CKD dose adjust
Gabapentin	Neuropathic	Chronic	DPN, PHN	Sedation; CKD dose adjust
Oxcarbazepine	Neuropathic	Chronic	Trigeminal neuralgia alt	Hyponatremia
Lamotrigine	Neuropathic (selected)	Chronic	Selected cases	Rash/SJS risk

SNRIs (Descending Inhibition Strength)

Drug	Primary Pain Type(s)	Acute vs Chronic	Best Clinical Use	Key Pearls / Major Cautions
Duloxetine	Neuropathic, nociplastic, chronic MSK	Chronic	DPN, fibromyalgia, chronic back pain	Strongest analgesic evidence; nausea; BP monitoring
Venlafaxine	Neuropathic	Chronic	Neuropathic alternative	Dose-dependent NE effect; withdrawal risk

TCAs (Analgesic Strength > Tolerability)

Drug	Primary Pain Type(s)	Acute vs Chronic	Best Clinical Use	Key Pearls / Major Cautions
Amitriptyline	Neuropathic, nociplastic	Chronic	Neuropathic pain + sleep	Most potent TCA; anticholinergic; QTc
Nortriptyline	Neuropathic	Chronic	Better tolerated TCA	Still anticholinergic

NMDA Antagonists

Drug	Primary Pain Type(s)	Acute vs Chronic	Best Clinical Use	Key Pearls / Major Cautions
Ketamine	Hyperalgesia, severe acute pain	Acute	Opioid-refractory pain	Very potent acute analgesic; dissociation; BP elevation
Methadone	Mixed, neuropathic component	Chronic	Severe chronic pain	NMDA activity + μ agonist; QTc; complex kinetics

Opioids (Most Potent → Least Potent Relative to Morphine)

Drug	Primary Pain Type(s)	Acute vs Chronic	Best Clinical Use	Key Pearls / Major Cautions
Fentanyl	Severe nociceptive	Acute	OR/ICU	~100× morphine potency; patch for opioid-tolerant only
Buprenorphine	Mixed	Chronic	Pain + OUD overlap	High receptor affinity; partial agonist; safer respiratory profile
Methadone	Mixed, neuropathic component	Chronic	Severe chronic pain	3–10× morphine; QTc; long half-life
Oxycodone	Severe nociceptive	Acute + Chronic	Severe acute pain	~1.5× morphine potency; misuse risk
Morphine	Severe nociceptive	Acute + Chronic	Reference opioid	Standard comparator
Hydrocodone	Moderate-severe nociceptive	Acute	Short-term acute pain	Often combined with APAP
Tapentadol	Mixed	Acute/Chronic	Severe pain w/ neuropathic component	μ + NE mechanism; less potent
Tramadol	Mixed	Acute/Chronic	Selected cases	Weakest μ effect; seizure risk; serotonin syndrome

Topical Agents

Drug	Primary Pain Type(s)	Acute vs Chronic	Best Clinical Use	Key Pearls / Major Cautions
Topical Lidocaine	Neuropathic	Chronic	PHN	Strong localized effect
Capsaicin	Neuropathic	Chronic	Peripheral neuropathy	Moderate effect; initial burning

Cannabinoids

Drug	Primary Pain Type(s)	Acute vs Chronic	Best Clinical Use	Key Pearls / Major Cautions
THC	Neuropathic (modest)	Chronic	Adjunct therapy	Psychoactive; variable response
CBD	Mixed	Chronic	Adjunct	Limited high-quality evidence

VI. Special Populations

See: Special Populations in Pain Management

Elderly
Chronic kidney disease
Liver disease
Pregnancy
History of substance use disorder

VII. Case-Based Clinical Applications

See: Case-Based Clinical Applications

Acute injury
Chronic low back pain
Diabetic neuropathy
Fibromyalgia
High-risk opioid patient

Guiding Clinical Principles

• Pain classification determines therapy • Chronic pain often reflects central amplification • Mechanism-directed prescribing improves outcomes • Opioids are powerful but limited tools • Multimodal therapy reduces risk