The Antinociceptive Effect of Sympathetic Block is Mediated by Transforming Growth Factor β in a Mouse Model of Radiculopathy.
10.1007/s12264-023-01062-5
- Author:
Debora Denardin LÜCKEMEYER
1
;
Wenrui XIE
1
;
Arthur Silveira PRUDENTE
1
;
Katherine A QUALLS
1
;
Raquel TONELLO
2
;
Judith A STRONG
1
;
Temugin BERTA
1
;
Jun-Ming ZHANG
3
Author Information
1. Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA.
2. Department of Molecular Pathobiology, Department of Neuroscience and Physiology, Neuroscience Institute, New York University, New York, NY, 10010, USA.
3. Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA. Jun-Ming.Zhang@uc.edu.
- Publication Type:Journal Article
- Keywords:
Cytokine;
Inflammation;
Radiculopathy;
Sympathetic;
TGF-β
- MeSH:
Mice;
Animals;
Receptor, Transforming Growth Factor-beta Type I/metabolism*;
Transforming Growth Factor beta/pharmacology*;
Transforming Growth Factor beta1/metabolism*;
Hyperalgesia/metabolism*;
Radiculopathy/metabolism*;
Pain/metabolism*;
Analgesics/pharmacology*;
Ganglia, Spinal/metabolism*
- From:
Neuroscience Bulletin
2023;39(9):1363-1374
- CountryChina
- Language:English
-
Abstract:
Although sympathetic blockade is clinically used to treat pain, the underlying mechanisms remain unclear. We developed a localized microsympathectomy (mSYMPX), by cutting the grey rami entering the spinal nerves near the rodent lumbar dorsal root ganglia (DRG). In a chemotherapy-induced peripheral neuropathy model, mSYMPX attenuated pain behaviors via DRG macrophages and the anti-inflammatory actions of transforming growth factor-β (TGF-β) and its receptor TGF-βR1. Here, we examined the role of TGF-β in sympathetic-mediated radiculopathy produced by local inflammation of the DRG (LID). Mice showed mechanical hypersensitivity and transcriptional and protein upregulation of TGF-β1 and TGF-βR1 three days after LID. Microsympathectomy prevented mechanical hypersensitivity and further upregulated Tgfb1 and Tgfbr1. Intrathecal delivery of TGF-β1 rapidly relieved the LID-induced mechanical hypersensitivity, and TGF-βR1 antagonists rapidly unmasked the mechanical hypersensitivity after LID+mSYMPX. In situ hybridization showed that Tgfb1 was largely expressed in DRG macrophages, and Tgfbr1 in neurons. We suggest that TGF-β signaling is a general underlying mechanism of local sympathetic blockade.
