The role of dorsal root ganglia alpha-7 nicotinic acetylcholine receptor in complete Freund’s adjuvant-induced chronic inflammatory pain
| Autor: | Lijuan Wang, Jinbao Li, Xiaoyu Zhang, Lina Huang, Jianhai Zhang, Fangxia Xu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Agonist alpha7 Nicotinic Acetylcholine Receptor Pyridines medicine.drug_class Freund's Adjuvant Immunology Pharmacology Benzylidene Compounds complex mixtures Mice Dorsal root ganglion Downregulation and upregulation Cell Line Tumor Ganglia Spinal medicine Animals Humans Pharmacology (medical) Neuroinflammation Inflammation TNF Receptor-Associated Factor 6 biology business.industry NF-kappa B Mice Inbred C57BL Disease Models Animal Nicotinic acetylcholine receptor medicine.anatomical_structure nervous system Gene Knockdown Techniques Neuroinflammatory Diseases Hyperalgesia biology.protein Tumor necrosis factor alpha sense organs Chronic Pain Inflammation Mediators NeuN medicine.symptom business |
| Zdroj: | Inflammopharmacology. 29:1487-1501 |
| ISSN: | 1568-5608 0925-4692 |
| DOI: | 10.1007/s10787-021-00873-0 |
| Popis: | Alpha-7 nicotinic acetylcholine receptor (α7 nAChR) was reported to have a critical role in the regulation of pain sensitivity and neuroinflammation. However, the expression level of α7 nAChR in dorsal root ganglion (DRG) and the underlying neuroinflammatory mechanisms associated with hyperalgesia are still unknown. In the present study, the expression and mechanism of α7 nAChR in chronic inflammatory pain was investigated using a complete Freund’s adjuvant (CFA)-induced chronic inflammatory pain model. Subsequently, a series of assays including immunohistochemistry, western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR) were performed. α7 nAChR was mostly colocalized with NeuN in DRG and upregulated after CFA injection. Microinjection of α7 nAChR siRNA into ipsilateral L4/5 DRGs aggravated the CFA-induced pain hypersensitivity. Intrathecal α7 nAChR agonist GTS-21 attenuated the development of CFA-induced mechanical and temperature-related pain hypersensitivities. In neuronal the SH-SY5Y cell line, the knockdown of α7 nAChRs triggered the upregulation of TRAF6 and NF-κB under CFA-induced inflammatory conditions, while agitation of α7 nAChR suppressed the TRAF6/NF-κB activation. α7 nAChR siRNA also exacerbated the secretion of pro-inflammatory mediators from LPS-induced SH-SY5Y cells. Conversely, α7 nAChR-specific agonist GTS-21 diminished the release of interleukin-1beta (IL-1β), IL-6, IL-8, and tumor necrosis factor-α (TNFα) in SH-SY5Y cells under inflammatory conditions. Mechanistically, the modulation of pain sensitivity and neuroinflammatory action of α7 nAChR may be mediated by the TRAF6/NF-κB signaling pathway. The findings of this study suggest that α7 nAChR may be potentially utilized as a therapeutic target for therapeutics of chronic inflammatory pain. |
| Databáze: | OpenAIRE |
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