Potentiation of the lateral habenula-ventral tegmental area pathway underlines the susceptibility to depression in mice with chronic pain.

Chronic pain often develops severe mood changes such as depression. However, how chronic pain leads to depression remains elusive and the mechanisms determining individuals' responses to depression are largely unexplored. Here we found that depression-like behaviors could only be observed in 67.9% of mice with chronic neuropathic pain, leaving 32.1% of mice with depression resilience. We determined that the spike discharges of the ventral tegmental area (VTA)-projecting lateral habenula (LHb) glutamatergic (Glu) neurons were sequentially increased in sham, resilient and susceptible mice, which consequently inhibited VTA dopaminergic (DA) neurons through a LHbGlu-VTAGABA-VTADA circuit. Furthermore, the LHbGlu-VTADA excitatory inputs were dampened via GABAB receptors in a pre-synaptic manner. Regulation of LHb-VTA pathway largely affected the development of depressive symptoms caused by chronic pain. Our study thus identifies a pivotal role of the LHb-VTA pathway in coupling chronic pain with depression and highlights the activity-dependent contribution of LHbGlu-to-VTADA inhibition in depressive behavioral regulation.

Rab11a in the spinal cord: an essential contributor to complete Freund's adjuvant-induced inflammatory pain in mice.

Inflammatory pain is a commonly observed clinical symptom in a range of acute and chronic diseases. However, the mechanism of inflammatory pain is far from clear yet. Rab11a, a small molecule guanosine triphosphate enzyme, is reported to regulate orofacial inflammatory pain in our previous works. However, the mechanism of Rab11a's involvement in the regulation of inflammatory pain remains obscure. Here, we aim to elucidate the potential mechanisms through which Rab11a contributes to the development of inflammatory pain in the spinal level. It's shown that neurons, rather than glial cells, were the primary cell type expressing Rab11a in the spinal dorsal horn (SDH). After intra-plantar injection of CFA, both the number of Fos/Rab11a-immunopositive neurons and the expression of Rab11a were increased. Administration of Rab11a-shRNA into the SDH resulted in significantly analgesic effect in mice with CFA injection. Application of Rab11a-shRNA also reduced the NMDA receptor-mediated excitatory post-synaptic current (EPSC) and the spike number of neurons in lamina II of the SDH in mice with CFA injection, without affecting the presynaptic glutamate release and the postsynaptic AMPA receptor-mediated EPSC. Our results thus suggest that the enhanced expression of neuronal Rab11a may be important for the process of inflammatory pain in mice with CFA injection, which is likely mediated by Rab11a's potentiation of the competence of post-synaptic NMDAR and spiking of SDH neurons.

Preservation versus non-preservation of the duodenal passage following total gastrectomy: a systematic review.

BACKGROUND: Various reconstruction procedures have been proposed for restoring the alimentary tract continuity after total gastrectomy. However, so far there is no consensus on the ideal post-gastrectomy reconstruction procedure. The necessity of preserving the duodenal passage is one of the major focuses of the debate concerning gastrointestinal reconstruction and is the objective of this study. METHODS: A systematic literature search of PubMed, EMBASE, the Cochrane Library, SCI, and Chinese Biomedical Literature Database (CBM) was carried out before March 2012 to obtain studies of randomized controlled trials (RCT). Analysis was performed using RevMan 5.0 software. RESULTS: Nine RCTs involving 642 participants met the selection criteria. The results of the meta-analyses showed that operative mortality and morbidity were not significantly different between the two procedures (preservation vs. non-preservation of duodenum). However, operative time was considerably prolonged by preserving the duodenal passage. Patients in the preservation group had an improved nutritional parameters (body weight, levels of serum iron and hemoglobin) in the short term (<6 months) after surgery. Beneficial effect on preventing postgastrectomy symptom (heartburn, dumping syndrome) was not found by maintaining the duodenal passage throughout a 2-year follow-up. Moreover, a qualitative measurement showed that no significant quality of life improvement for patients with a preserved duodenal passage. CONCLUSION: This systematic review failed to demonstrate obvious advantage in preserving duodenal passage after total gastrectomy.