The inhibition of spinal synaptic plasticity mediated by activation of AMP-activated protein kinase signaling alleviates the acute pain induced by oxaliplatin.

The inhibition of spinal synaptic plasticity mediated by activation of AMP-activated protein kinase signaling alleviates the acute pain induced by oxaliplatin. Exp Neurol. 2016 Nov 14;: Authors: Ling YZ, Li ZY, Ou-Yang HD, Ma C, Wu SL, Wei JY, Ding HH, Zhang XL, Liu M, Liu CC, Huang ZZ, Xin WJ Abstract Our recent findings demonstrated that oxaliplatin entering CNS may directly induce spinal central sensitization, and contribute to the rapid development of CNS-related side effects including acute pain during chemotherapy. However, the mechanism is largely unclear. In the current study, we found that the amplitude of C-fiber-evoked field potentials was significantly increased and the expression of phosphorylated mammalian AMP-activated protein kinase α (AMPKα) was markedly decreased following high frequency stimulation (HFS) or single intraperitoneal injection of oxaliplatin (4mg/kg). Spinal local application of AMPK agonist metformin (25μg) prevented the long term potentiation (LTP) induction and the activation of mTOR/p70S6K signal pathway, and significantly attenuated the acute thermal hyperalgesia and mechanical allodynia following single oxaliplatin treatment. Importantly, we found that incubation of low concentration oxaliplatin at dose of 6.6nM (the detected concentration in CSF following a single intraperitoneal injection of oxaliplatin) also significantly inhibited the AMPKα activation and increased the amplitude of sEPSCs...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research