Perisciatic Nerve Dexmedetomidine Alleviates Spinal Oxidative Stress and Improves Peripheral Mitochondrial Dynamic Equilibrium in a Neuropathic Pain Mouse Model in an AMPK-Dependent Manner.
Yang MuYang MeiYaohua ChenYu-Ping LiDan ZhuJian CuiLe-Hua YuPublished in: Disease markers (2022)
Neuropathic pain (NPP) is a debilitating clinical condition that presently has few effective treatments. NPP is caused by uncontrolled central oxidative stress and inflammation. Preliminary studies indicate that dexmedetomidine (DEX), an agonist of the alpha-2 adrenergic receptor, is beneficial for treating NPP. In this paper, the effects of administering DEX around injured nerves in a chronic constriction injury- (CCI-) induced neuropathic pain mouse model are investigated. According to the results, the perineural DEX significantly reversed the decline in the mechanical threshold and thermal latency in CCI mice ( p < 0.001). In the peripherally affected ischiadic nerve, the perineuronal DEX upregulated the expressions of pAMPK, OPA1, and SNPH but not Drp1 or KIF5B. The aforementioned effects of administering DEX can be partially reversed by compound C, a selective and reversible inhibitor of AMP-activated protein kinase (AMPK). Furthermore, it was found that perineural DEX significantly inhibited the CCI-induced upregulation of the immediate early gene c-Fos, overexpression of the inflammatory factors tumor necrosis factor-alpha (TNF- α ) and interleukin-6 (IL-6), attenuation of the NADH dehydrogenase complexes I, II, III, and IV, and the repression of ATP, SOD, and GSH in the dorsal horn of the spinal cord (DHSC) ( p < 0.01). These findings indicate that perineuronal DEX protected the injured ischiadic nerves and attenuated neuropathic pain via AMPK activation to improve energy supply in the peripheral injured nerves, alleviate the inflammatory factor release, and inhibit oxidative stress in the DHSC.
Keyphrases
- neuropathic pain
- oxidative stress
- spinal cord
- diabetic rats
- protein kinase
- mouse model
- spinal cord injury
- dna damage
- ischemia reperfusion injury
- induced apoptosis
- skeletal muscle
- cell proliferation
- high glucose
- drug induced
- dna methylation
- copy number
- heat stress
- adipose tissue
- metabolic syndrome
- signaling pathway
- mass spectrometry
- binding protein
- insulin resistance
- endothelial cells
- long non coding rna