Spinal cord stimulation reduces cardiac pain through microglial deactivation in rats with chronic myocardial ischemia
| Autor: | Jia-Hao Ren, Yun-Qing Li, Xiaochen Wu, Liu Jingzhen, Jinbao Zhang, Jian Wang, Siyi He, Xi-Qiang Wu, Yi Sun, Mingming Zhang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Spinal Cord Dorsal Horn Cancer Research Analgesic Central nervous system Myocardial Ischemia microglia Pharmacology p38 Mitogen-Activated Protein Kinases Biochemistry Angina Pectoris Rats Sprague-Dawley Angina Genetics medicine Animals chronic myocardial ischemia Molecular Biology Neuroinflammation Spinal Cord Stimulation integumentary system Microglia business.industry Calcium-Binding Proteins Microfilament Proteins Chronic pain Articles medicine.disease Spinal cord Rats Disease Models Animal medicine.anatomical_structure Nociception Gene Expression Regulation nervous system Oncology Astrocytes Chronic Disease Neuroinflammatory Diseases Cytokines Molecular Medicine business cardiac pain |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| DOI: | 10.3892/mmr.2021.12475 |
| Popis: | Angina pectoris is cardiac pain that is a common clinical symptom often resulting from myocardial ischemia. Spinal cord stimulation (SCS) is effective in treating refractory angina pectoris, but its underlying mechanisms have not been fully elucidated. The spinal dorsal horn is the first region of the central nervous system that receives nociceptive information; it is also the target of SCS. In the spinal cord, glial (astrocytes and microglia) activation is involved in the initiation and persistence of chronic pain. Thus, the present study investigated the possible cardiac pain‑relieving effects of SCS on spinal dorsal horn glia in chronic myocardial ischemia (CMI). CMI was established by left anterior descending artery ligation surgery, which induced significant spontaneous/ongoing cardiac pain behaviors, as measured using the open field test in rats. SCS effectively improved such behaviors as shown by open field and conditioned place preference tests in CMI model rats. SCS suppressed CMI‑induced spinal dorsal horn microglial activation, with downregulation of ionized calcium‑binding adaptor protein‑1 expression. Moreover, SCS inhibited CMI‑induced spinal expression of phosphorylated‑p38 MAPK, which was specifically colocalized with the spinal dorsal horn microglia rather than astrocytes and neurons. Furthermore, SCS could depress spinal neuroinflammation by suppressing CMI‑induced IL‑1β and TNF‑α release. Intrathecal administration of minocycline, a microglial inhibitor, alleviated the cardiac pain behaviors in CMI model rats. In addition, the injection of fractalkine (microglia‑activating factor) partially reversed the SCS‑produced analgesic effects on CMI‑induced cardiac pain. These results indicated that the therapeutic mechanism of SCS on CMI may occur partially through the inhibition of spinal microglial p38 MAPK pathway activation. The present study identified a novel mechanism underlying the SCS‑produced analgesic effects on chronic cardiac pain. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|