Liu, X.* ; Tian, Y.* ; Meng, Z.* ; Chen, Y.* ; Ho, I.H.* ; Choy, K.W.* ; Lichtner, P. ; Wong, S.H.* ; Yu, J.* ; Gin, T.* ; Wu, W.K.* ; Cheng, C.H.* ; Chan, M.T.*
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
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Keywords
Formyl Peptide Receptor; Neuropathic Pain; Spinal-cord; Serine Proteases; Growth-factor; Inflammation; Neutrophils; Identification; Prevalence; Astrocytes
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Language
english
Publication Year
2015
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2015
ISSN (print) / ISBN
0003-3022
e-ISSN
1528-1175
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Volume: 123,
Issue: 4,
Pages: 838-850
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Lippincott Williams & Wilkins
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Philadelphia
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Peer reviewed
POF-Topic(s)
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-500700-001
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Erfassungsdatum
2015-08-15