RESUMO
Thousand and one amino acid kinase 2 (TAOK2) is a member of the mammalian sterile 20 kinase family and is implicated in neurodevelopmental disorders; however, its role in neuropathic pain remains unknown. Here, we found that TAOK2 was enriched and activated after chronic constriction injury (CCI) in the rat spinal dorsal horn. Meanwhile, cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling was also activated with hyperalgesia. Silencing TAOK2 reversed hyperalgesia and suppressed the activation of cGAS-STING signaling induced by CCI, while pharmacological activation of TAOK2 induced pain hypersensitivity and upregulation of cGAS-STING signaling in naive rats. Furthermore, pharmacological inhibition or gene silencing of cGAS-STING signaling attenuated CCI-induced hyperalgesia. Taken together, these data demonstrate that the activation of spinal TAOK2 contributes to CCI-induced hyperalgesia via cGAS-STING signaling activation, providing new molecular targets for the treatment of neuropathic pain.
RESUMO
Background: Although commonly used for the treatment of descending aortic dissection, endovascular repair is challenging for ascending aortic pseudoaneurysms. Rapid ventricular pacing (RVP), a method that temporarily impedes cardiac output by stopping ventricular activity, heralds potential benefits for thoracic endovascular aortic repair (TEVAR) during precision landing. Recently, we successfully treated an anastomosis pseudoaneurysm after the Bentall procedure using TEVAR assisted by RVP. Case report: A 69-year-old male was admitted to our hospital with a ascending aortic anastomosis pseudoaneurysm. He had undergone a Bentall procedure and a coronary artery bypass grafting nine years prior. After extensive consultation, the decision was made to perform TEVAR with the assistance of RVP. After a covered stent graft was delivered to the precise location of the ascending aorta, RVP was performed at a frequency of 180 beats/min with a pacemaker. When a flattened arterial blood wave of <50 mmHg was observed, the stent graft was released precisely between the opening of the coronary graft and innominate artery. Angiography revealed the presence of an endoleak; therefore, a set of interlock coils were packed into the aneurysm. Subsequent angiography showed intact blood flow in the aorta, superior arch branches, and coronary graft vessels. The patient recovered uneventfully after the procedure. He was discharged six days later and was doing well at the eight-month follow-up. Conclusion: The case indicates that TEVAR assisted by RVP is a promising combination for ascending aortic pseudoaneurysm in selected patients.