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Open Access Green as soon as Postprint is submitted to ZB.
Up-regulation of cathepsin G in the development of chronic postsurgical pain: An experimental and clinical genetic study.
Anesthesiology 123, 838-850 (2015)
BACKGROUND: Proteases have been shown to modulate pain signaling in the spinal cord and may contribute to the development of chronic postsurgical pain. By using peripheral inflammation in rats as a chronic pain model, the authors identified the deregulation of proteases and their inhibitors as a hallmark of chronic pain development using a genome-wide screening approach. METHODS: A microarray analysis was performed and identified spinal cathepsin G (CTSG) as the most up-regulated gene in rats with persistent hyperalgesia after intraplantar injection of complete Freund's adjuvant (n = 4). Further experiments were performed to elucidate the mechanisms of CTSG-induced hyperalgesia by intrathecally applying specific CTSG inhibitor (n = 10). The authors also evaluated the association between CTSG gene polymorphisms and the risk of chronic postsurgical pain in 1,152 surgical patients. RESULTS: CTSG blockade reduced heat hyperalgesia, accompanied by a reduction in neutrophil infiltration and interleukin 1β levels in the dorsal horns. In the gene association study, 246 patients (21.4%) reported chronic postsurgical pain at 12-month follow-up. Patients with AA genotypes at polymorphisms rs2070697 (AA-15.3%, GA-24.1%, and GG-22.3%) or rs2236742 (AA-6.4%, GA-20.4%, and GG-22.6%) in the CTSG gene had lower risk for chronic postsurgical pain compared with wild-types. The adjusted odds ratios were 0.67 (95% CI, 0.26 to 0.99) and 0.34 (95% CI, 0.21 to 0.98), respectively. CONCLUSIONS: This study demonstrated that CTSG is a pronociceptive mediator in both animal model and human study. CTSG represents a new target for pain control and a potential marker to predict patients who are prone to develop chronic pain after surgery.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Formyl Peptide Receptor; Neuropathic Pain; Spinal-cord; Serine Proteases; Growth-factor; Inflammation; Neutrophils; Identification; Prevalence; Astrocytes
ISSN (print) / ISBN
0003-3022
e-ISSN
1528-1175
Journal
Anesthesiology
Quellenangaben
Volume: 123,
Issue: 4,
Pages: 838-850
Publisher
Lippincott Williams & Wilkins
Publishing Place
Philadelphia
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Human Genetics (IHG)