Spinal astrocytic EAATs mediate endothelin-1-induced breakthrough cancer pain in mice.
1/5 보강
[BACKGROUND] Breakthrough cancer pain (BTcP) lacks representative animal models.
APA
Jiang S, Huang D, et al. (2026). Spinal astrocytic EAATs mediate endothelin-1-induced breakthrough cancer pain in mice.. Neurological research, 1-14. https://doi.org/10.1080/01616412.2025.2612305
MLA
Jiang S, et al.. "Spinal astrocytic EAATs mediate endothelin-1-induced breakthrough cancer pain in mice.." Neurological research, 2026, pp. 1-14.
PMID
41496577
Abstract
[BACKGROUND] Breakthrough cancer pain (BTcP) lacks representative animal models. The roles of spinal excitatory amino acid transporters (EAATs) in BTcP remain unclear.
[METHODS] We established a modified BTcP mouse model using lung cancer bone metastasis and endothelin-1 (ET-1) injections once daily on postoperative days 16-18, with validation through behavioral and electrophysiological assessments. Spinal EAAT1, EAAT2 and connexin 43 (Cx43) were investigated. Mice were administered intrathecal ceftriaxone (EAAT2 activator), Gap26 (gap junction blocker), or control agents.
[RESULTS] The BTcP model showed reduced pain thresholds and function, accompanied by decreased EAAT1/EAAT2 and increased phosphorylated C×43 (p-Cx43) in spinal astrocytes. Ceftriaxone reversed pain hypersensitivity, upregulated EAAT2, and reduced p-Cx43 without affecting EAAT1/total Cx43. Gap26 increased EAAT1/EAAT2, decreased Cx43/p-Cx43, and alleviated pain behaviors.
[CONCLUSION] This optimized ET-1 model provides a robust platform for BTcP research. Spinal EAATs, downregulation and C×43 activation, contribute to BTcP pathogenesis, and both are potential therapeutic targets of BTcP.
[METHODS] We established a modified BTcP mouse model using lung cancer bone metastasis and endothelin-1 (ET-1) injections once daily on postoperative days 16-18, with validation through behavioral and electrophysiological assessments. Spinal EAAT1, EAAT2 and connexin 43 (Cx43) were investigated. Mice were administered intrathecal ceftriaxone (EAAT2 activator), Gap26 (gap junction blocker), or control agents.
[RESULTS] The BTcP model showed reduced pain thresholds and function, accompanied by decreased EAAT1/EAAT2 and increased phosphorylated C×43 (p-Cx43) in spinal astrocytes. Ceftriaxone reversed pain hypersensitivity, upregulated EAAT2, and reduced p-Cx43 without affecting EAAT1/total Cx43. Gap26 increased EAAT1/EAAT2, decreased Cx43/p-Cx43, and alleviated pain behaviors.
[CONCLUSION] This optimized ET-1 model provides a robust platform for BTcP research. Spinal EAATs, downregulation and C×43 activation, contribute to BTcP pathogenesis, and both are potential therapeutic targets of BTcP.
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