Chronic neuropathic pain: Pathomechanism and pharmacology

L. Urban, I. Nagy, S. J. Bevan

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Neuropathic pain syndromes form a group of loosely connected diseases linked by the common presence of injury/damage to the peripheral sensory system and the resulting effect: chronic pain. Treatment of patients suffering from neuropathic pain is one of the most challenging clinical tasks as classical painkillers such as opioids and nonsteroidal anti-inflammatory drugs lack antinociceptive effect in these syndromes. The recent development of various animal models aided our understanding of neuropathic pain and provided targets for analgesic intervention. The discovery of abnormal, ectopic activity in injured primary afferents, sprouting of large calibre primary afferent fibres to the superficial dorsal horn, and changes in protein expression in DRG (dorsal root ganglion) cells after injury has highlighted differences between the pathomechanisms of nociceptive and neuropathic pain and explained the lack of efficacy of commonly used analgesic drugs. Recent clinical trials based on considerations from animal studies have proved, at least partly, that targeting these mechanisms could lead to more efficacious antinociceptive agents for neuropathic pain syndromes. There are three major sites of interventions: (1) abnormal, ectopic activity of the injured afferents, (2) increased release of transmitters in the spinal cord, and (3) enhanced neuronal activity in the spinal dorsal horn. To date, there has been no breakthrough in the clinical treatment of neuropathic pain; however, data from recent preclinical studies and clinical trials with anticonvulsants, gabapentin-like molecules, Ca (calcium)-channel blocking agents, GABAB (y-amino butyric acid) receptor agonists, and NMDA (N-methyl-D-asparate) receptor antagonists promise the development of effective pain relief for patients suffering from neuropathic pain.

Original languageEnglish
Pages (from-to)159-166
Number of pages8
JournalDrug Development Research
Volume54
Issue number3
DOIs
Publication statusPublished - Jan 1 2001

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Keywords

  • Peripheral nerve injury
  • Primary sensory neurons
  • Review
  • Spinal cord

ASJC Scopus subject areas

  • Drug Discovery

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