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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