Spinal cord stimulation reduces cardiac pain through microglial deactivation in rats with chronic myocardial ischemia.

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 pain­relieving 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 CMI­induced spinal dorsal horn microglial activation, with downregulation of ionized calcium­binding adaptor protein­1 expression. Moreover, SCS inhibited CMI­induced spinal expression of phosphorylated­p38 MAPK, which was specifically colocalized with the spinal dorsal horn microglia rather than astrocytes and neurons. Furthermore, SCS could depress spinal neuroinflammation by suppressing CMI­induced IL­1ß and TNF­α release. Intrathecal administration of minocycline, a microglial inhibitor, alleviated the cardiac pain behaviors in CMI model rats. In addition, the injection of fractalkine (microglia­activating factor) partially reversed the SCS­produced analgesic effects on CMI­induced 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 SCS­produced analgesic effects on chronic cardiac pain.

The molecular mechanism of aminoguanidine-mediated reduction on the brain edema after surgical brain injury in rats.

The study investigated the effect of aminoguanidine (AG) on inducible nitric oxide synthase (iNOS), aquaporin-4 (AQP4), malondialdehyde (MDA) and glutathione (GSH) levels in surgical brain injury (SBI) in rats. AG (75, 150 and 300 mg/kg, i.p.) was administered immediately following surgical resection. Using an SBI model, the absence of iNOS protein in any brain tested (sham-operated group, SBI group and SBI+AG group) at 24 h after SBI was confirmed by Western blot analysis. The expression of AQP4 protein in brain tissue at the edge of the resection site increased at 24 h after SBI, which could be greatly attenuated by the treatment with AG (150 mg/kg), while AG at the dose of 75 mg/kg or 300 mg/kg had no significant effect on it. In addition, there was a marked decrease of MDA values and a great increase of the GSH levels at 24 h after SBI in SBI+AG (150 mg/kg) group compared with SBI group. Whereas AG (300 mg/kg) elevated oxidative stress compared with SBI group. Our results indicate that the anti-edematous effect of AG observed in our study is dose-dependent and unlikely related to its inhibition effect on iNOS and may attribute to its roles on the regulation of AQP4 expression and antioxidative property at brain tissue after SBI.