Ischemic postconditioning reduces spinal cord ischemia-reperfusion injury through ATP-sensitive potassium channel.

STUDY DESIGN: Animal study. OBJECTIVES: Explore the neuroprotective effect of remote limb ischemic postconditioning (Post C) in spinal cord ischemic reperfusion injury (SCII) and related mechanisms. SETTING: Anesthesiology Laboratory of Southwest Medical University. METHODS: We established a rabbit SCII model and processed it with Post C. To evaluate the neural function, spinal cord tissue was taken 48 h later, normal neurons were evaluated by HE staining, and the expression of ATP-sensitive potassium channel (KATP) marker molecule Kir6.2 was detected by Western blot. Immunofluorescence detection of spinal cord Iba-1 expression, ELISA detection of M1 type microglia marker iNOS and M2 type microglia marker Arg, and Western blot detection of NF-κB and IL-1ß expression. Through these experiments, we will explore the protective effect of Post C in SCII, observe the changes in the protective effect after using KATP blockers, and verify that Post C can play a neuroprotective effect in SCII by activating KATP. RESULTS: We observed that Post C significantly improved exercise ability and the number of spinal motor neurons in the SCII model. Microglia are activated and expression of M1 microglia in the spinal cord was decreased, while M2 was increased. This neuroprotective effect was reversed by the nonspecific KATP inhibitor. CONCLUSION: Post C has a neuroprotective effect on SCII, and maybe a protective effect produced by activating KATP to regulate spinal microglia polarization and improve neuroinflammation.

Activation of SK3 channel plays a pivotal role in modulation of trigeminal neuralgia.

Objective: To investigate whether small conductance Ca2+ activatedK+ channels; Trigeminal ganglion; Trigeminal neuralgia. (SK3) exists in normal rats' trigeminal ganglions (TG) and its effect on their pain thresholds.Methods: In total, 110 healthy adult male Sprague-Dawley (SD) rats were involved in this study. Ten rats were dissected to collect their liver tissues, TG and DRG. The rest of the rats were randomly assigned to either the experimental group or the control group. The animal model of trigeminal neuralgia (TN) was established by infraorbital nerve ligation. The expression of SK3 channels in their livers, TG and dorsal root ganglions (DRG) were detected. And different doses of SK3 channel activator and inhibitor were administered to the rats in both groups 15 days after the operation; meanwhile, their pain thresholds were also measured.Results: The expression of SK3 channel was found in TG. In the experimental group, the pain threshold was significantly decreased and there was a decreased level of SK3 than that in the control group at 15 days after operation. The administration of SK3 channel agonist (CyPPA) could significantly improve the pain threshold, while, the pain threshold decreased after administration of SK3 channel antagonist (Apamin).Conclusion: The SK3 channel may play a pivotal role in the pathogenesis of trigeminal neuralgia, and it may be one of the potential targets for the treatment of trigeminal neuralgia.

c-Abl-p38α signaling pathway mediates dopamine neuron loss in trigeminal neuralgia.

Trigeminal neuralgia is a common neuropathic pain in the head and face. The pathogenesis of trigeminal neuralgia is complex, and so far, the pathogenesis of trigeminal neuralgia involving peripheral and central nervous inflammation theory has not been explained clearly. The loss of dopamine neurons in striatum may play an important role in the development of trigeminal nerve, but the reason is not clear. C-Abl is a nonreceptor tyrosine kinase, which can be activated abnormally in the environment of neuroinflammation and cause neuron death. We found that in the rat model of infraorbital nerve ligation trigeminal neuralgia, the pain threshold decreased, the expression of c-Abl increased significantly, the downstream activation product p38 was also activated abnormally and the loss of dopamine neurons in striatum increased. When treated with imatinib mesylate (STI571), a specific c-Abl family kinase inhibitor, the p38 expression was decreased and the loss of dopaminergic neurons was reduced. The mechanical pain threshold of rats was also improved. In conclusion, c-abl-p38 signaling pathway may play an important role in the pathogenesis of trigeminal neuralgia, and it is one of the potential targets for the treatment of trigeminal neuralgia.