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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:

Anti-Inflammatory Agents

Mechanism:

Decrease prostaglandin-mediated sensitization.

Voltage-Gated Sodium Channel Antagonists

Lidocaine
Suzetrigine (Nav 1.8 selective antagonist)

Mechanism:

Block action potential propagation in nociceptors.

Gabapentinoids

Mechanism:

Bind α2δ calcium channel subunit → decrease glutamate & substance P release.

Serotonin & Norepinephrine Reuptake Inhibitors

Mechanism:

Enhance descending inhibitory pathways.

NMDA Receptor Antagonists

Ketamine

Mechanism:

Reduce central sensitization and wind-up.

Opioid Analgesics

Opioids

Mechanism:

μ-receptor activation → decrease ascending pain transmission.

NK1 Receptor Antagonists (Investigational for Pain)

NK1 Antagonists

Mechanism:

Block Substance P at NK1 receptors.

Clinical role in chronic pain remains limited.

Nerve Growth Factor (NGF) Antibodies

Tanezumab
Fasinumab

Mechanism:

Block NGF-mediated nociceptor sensitization.

Not currently approved due to safety concerns.

Cannabinoids

THC
CBD

Mechanism:

CB1/CB2 receptor modulation (evidence evolving).

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

Pharm Reference: Pain Drug Reference (Mechanism → Best Use)

Drug	Primary Pain Type(s)	Acute vs Chronic	Best Clinical Use	Key Pearls / Major Cautions

NSAIDs
Ibuprofen	Nociceptive (somatic), inflammatory	Acute + Chronic	MSK pain, OA flares	GI/renal risk; ↑BP; avoid CKD/dehydration; ceiling effect
Naproxen	Nociceptive, inflammatory	Acute + Chronic	OA, tendinitis	Similar NSAID risks; longer duration
Diclofenac	Nociceptive, inflammatory	Acute + Chronic	OA (esp topical)	Higher CV risk; topical less systemic exposure
Indomethacin	Nociceptive, inflammatory	Acute	Acute gout	More CNS/GI adverse effects
Celecoxib	Nociceptive, inflammatory	Acute + Chronic	OA/RA, GI-risk patients	COX-2 selective → less GI ulcer risk; still CV/renal risk

Acetaminophen
Acetaminophen	Nociceptive (mild)	Acute + Chronic	Baseline analgesic, combination therapy	Liver toxicity risk; safer in CKD than NSAIDs; ceiling effect

Corticosteroids
Prednisone	Inflammatory pain	Acute (bursts)	Radiculitis flares	Not analgesic; treat inflammation; hyperglycemia, mood, BP
Methylprednisolone	Inflammatory	Acute	Dose packs/flares	Short courses preferred
Dexamethasone	Inflammatory, cancer-related edema	Acute	Severe inflammation/edema	Potent/long acting; insomnia, hyperglycemia

Na⁺ Channel Antagonists
Lidocaine	Neuropathic (localized), procedural	Acute + Chronic	Topical neuropathic pain; procedures	Helpful in PHN; systemic toxicity if misused
Suzetrigine	Nociceptive (acute), mixed	Acute	Oral peripheral analgesia (Nav1.8)	Emerging agent

Antiepileptics
Gabapentin	Neuropathic	Chronic	DPN, PHN	Sedation; CKD dose adjust
Pregabalin	Neuropathic, nociplastic	Chronic	DPN, fibromyalgia	Edema; CKD dose adjust
Carbamazepine	Neuropathic (paroxysmal)	Chronic	Trigeminal neuralgia	Hyponatremia; CBC/LFT monitoring
Oxcarbazepine	Neuropathic	Chronic	Trigeminal neuralgia alt	Hyponatremia
Lamotrigine	Neuropathic (selected)	Chronic	Selected cases	Rash/SJS risk

SNRIs
Duloxetine	Neuropathic, nociplastic, chronic MSK	Chronic	DPN, fibromyalgia, chronic back pain	Nausea; BP monitoring
Venlafaxine	Neuropathic	Chronic	Neuropathic alt	Withdrawal risk

TCAs
Amitriptyline	Neuropathic, nociplastic	Chronic	Neuropathic pain + sleep	Anticholinergic; QTc
Nortriptyline	Neuropathic	Chronic	Better tolerated TCA	Still anticholinergic

NMDA Antagonists
Ketamine	Hyperalgesia, severe acute pain	Acute	Opioid-refractory pain	Dissociation; BP elevation
Methadone	Mixed, neuropathic component	Chronic	Severe chronic pain	QTc; complex kinetics

Opioids
Morphine	Severe nociceptive	Acute + Chronic	Severe pain, cancer pain	Constipation; respiratory depression
Oxycodone	Severe nociceptive	Acute + Chronic	Severe acute pain	Misuse risk
Hydrocodone	Moderate-severe nociceptive	Acute	Short-term acute pain	Often combined with APAP
Fentanyl	Severe pain	Acute	OR/ICU	Patch for opioid-tolerant only
Buprenorphine	Mixed	Chronic	Pain + OUD overlap	Partial agonist
Tramadol	Mixed	Acute/Chronic	Selected cases	Seizure risk; serotonin syndrome
Tapentadol	Mixed	Acute/Chronic	Severe pain w/ neuropathic component	μ + NE mechanism