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Updated: Sep 5, 2025
Chronic Post-Ischemia Pain Model for Complex Regional Pain Syndrome Type-I in Rats
Published on: January 21, 2020
Discovery of novel targets in a complex regional pain syndrome mouse model by transcriptomics: TNF and JAK-STAT
Krisztina Pohóczky1, József Kun2, Nikolett Szentes3
1Faculty of Pharmacy, Department of Pharmacology, University of Pécs, H-7624 Pécs, Hungary; Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, H-7624 Pécs, Hungary; János Szentágothai Research Centre & Centre for Neuroscience, University of Pécs, H-7624 Pécs, Hungary.
Abstract:
Complex Regional Pain Syndrome (CRPS) represents severe chronic pain, hypersensitivity, and inflammation induced by sensory-immune-vascular interactions after a small injury. Since the therapy is unsatisfactory, there is a great need to identify novel drug targets. Unbiased transcriptomic analysis of the dorsal root ganglia (DRG) was performed in a passive transfer-trauma mouse model, and the predicted pathways were confirmed by pharmacological interventions. In the unilateral L3-5 DRGs 125 genes were differentially expressed in response to plantar incision and injecting IgG of CRPS patients. These are related to inflammatory and immune responses, cytokines, chemokines and neuropeptides. Pathway analysis revealed the involvement of Tumor Necrosis Factor (TNF) and Janus kinase (JAK-STAT) signaling. The relevance of these pathways was proven by abolished CRPS IgG-induced hyperalgesia and reduced microglia and astrocyte markers in pain-associated central nervous system regions after treatment with the soluble TNF alpha receptor etanercept or JAK inhibitor tofacitinib. These results provide the first evidence for CRPS-related neuroinflammation and abnormal cytokine signaling at the level of the primary sensory neurons in a translational mouse model and suggest that etanercept and tofacitinib might have drug repositioning potentials for CRPS-related pain.
Insights
New research in a mouse model reveals that targeting Tumor Necrosis Factor (TNF) and Janus kinase (JAK-STAT) signaling pathways can reduce Complex Regional Pain Syndrome (CRPS) pain and neuroinflammation, suggesting potential new treatments.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Complex Regional Pain Syndrome (CRPS) is a debilitating chronic pain condition with limited therapeutic options.
- Understanding the molecular mechanisms underlying CRPS is crucial for identifying novel drug targets.
Purpose of the Study:
- To investigate the transcriptomic changes in dorsal root ganglia (DRG) associated with CRPS.
- To identify key signaling pathways involved in CRPS pathogenesis.
- To evaluate the therapeutic potential of targeting identified pathways in a preclinical model.
Main Methods:
- Unbiased transcriptomic analysis of DRG in a passive transfer-trauma mouse model.
- Pharmacological intervention using etanercept (TNF inhibitor) and tofacitinib (JAK inhibitor).
- Assessment of hyperalgesia and neuroinflammation markers (microglia, astrocytes) in the central nervous system.
Main Results:
- 125 differentially expressed genes in DRG related to inflammatory and immune responses, cytokines, chemokines, and neuropeptides.
- Tumor Necrosis Factor (TNF) and Janus kinase (JAK-STAT) signaling pathways were identified as critical.
- Treatment with etanercept or tofacitinib abolished CRPS IgG-induced hyperalgesia and reduced neuroinflammation.
Conclusions:
- This study provides the first evidence of CRPS-related neuroinflammation and abnormal cytokine signaling in primary sensory neurons using a translational mouse model.
- Etanercept and tofacitinib show potential for drug repositioning in treating CRPS-related pain.
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