Wutoutang Modulation Hippocampal BDNF/TrkB Pathway to Relieve Pain-emotion Co-curation / 中国实验方剂学杂志

ABSTRACT

<b>Objective:To explore the mediating effect of Wutoutang (WTT) on brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) pathway in hippocampus and to clarify the mechanism of therapeutic action of WTD on pain-emotion comorbidity by inhibiting neuropathic pain (NP) preliminarily. <b>Method:The mice were divided into sham group, spinal cord ligation (SNL) group, Wutoutang (WTT) group, Wutoutang-ANA12 antagonist (WTT-ANA12) group, pregabalin (PGB) group, Fluoxetine Hydrochloride (FLU) group randomly. Mice were fixed with the drug delivery cannula for hippocampal CA3.The L5 spinal cord of mice were tightly ligated but sham group (only exposed). During the 10-16^th day after surgery, WTT, WTT-ANA12 groups were gavaged with 126 mg·kg^-1 WTT, PGB and FLU groups were respectively given 25 mg·kg^-1 PGB and 3 mg·kg^-1 FLU, sham and SNL groups were given the physiological saline once a day. Then, 50 nmol·L^-1 ANA12 were given to the hippoicampal CA3 of the WTT-ANA12 mice by drug delivery cannula, and physiological saline were given to the others on the 10-16^th day after surgery. Mechanical pain were detected by Von Frey tests, anxiety and depression behaviors were separately detected by the open field and the tail tailing experiments, while the morphology of CA3 pyramidal neurons were qualified by the Golgi-staining. <b>Result:Compared with sham group, significant decreases of the mechanical pain thresholds, decreases of the duration time in the open field, as well as the increases of the no-struggling time during the tail-suspension were detected in the SNL mice(<italic>P</italic><0.01). In addition, as illustrated by the Golgi-staining, the atrophy of hippocampal pyramidal neurons were found in SNL mice as compared with sham(<italic>P</italic><0.05, <italic>P</italic><0.01). On the contrary, as compared to the SNL, significant increases of the mechanical pain thresholds, increases of the duration time in the open field, the decreases of the no-struggling time during the tail-suspension(<italic>P</italic><0.01), as well as the morphological improvements of the hippocampal CA3 pyramidal neurons were detected in the WTT mice. Furthermore, after 7 d hippocampal injections, There is no significant distinction of the mechanical pain thresholds, the duration time in the open field, the no-struggling time during the tail-suspension, as well as the atrophy of hippocampal neurons were detected in the WTT-ANA12 groups as compared with SNL. <b>Conclusion:The data suggested that the effective inhibition of WTT on SNL-induced vertebral neuron injury in hippocampus CA3 and pain-emotion disorder, which might attribute to it' s regulation of BDNF/TrkB pathway in hippocampus.