Clin Pain.  2025 Dec;24(2):106-114. 10.35827/cp.2025.24.2.106.

Understanding Pain Management through Pathways: A Mechanism-Based Review of Analgesics

• Park M
• Do JG

• KMID: 2575718
• DOI: http://doi.org/10.35827/cp.2025.24.2.106

Abstract

Pain management is a critical therapeutic goal in medicine. This review examines the mechanisms of various analgesics based on our understanding of pain pathways. Pain involves complex processes from nociception to perception, consisting of five key stages: transduction, conduction, transmission, modulation, and perception. Peripheral pain modulation occurs through inflammatory mediators like prostaglandins, bradykinin, and nerve growth factors. At the spinal level, synaptic transmission via glutamate receptors and inhibitory neurotransmitters plays a crucial role, while descending pathways from the periaqueductal gray matter and endogenous opioid systems provide central control. Understanding these mechanisms enables rational pharmacotherapy selection. Nonsteroidal anti-inflammatory drugs primarily act by inhibiting cyclooxygenase enzymes, while acetaminophen works through multiple central mechanisms. Opioid analgesics activate μ, δ, and κ receptors, modulating pain transmission at spinal and supraspinal levels. Anticonvulsants target voltage-gated ion channels, particularly effective for neuropathic pain, while antidepressants enhance descending inhibitory pathways. Recent advances have identified novel targets, including specific transient receptor potential channels, sodium channel subtypes, and neuroglial modulators. Precision medicine approaches incorporating pharmacogenomics and biomarkers are increasingly relevant for personalized pain management. This review provides a comprehensive analysis of pain modulation mechanisms and their clinical implications, offering practical guidance for mechanism-based analgesic selection.

Keyword

Pain; Analgesics; Mechanism of action; Pharmacotherapy; Pain control