Previous reports have suggested that physical and psychological stresses may trigger fibromyalgia (FM). Stress is an important risk factor in the development of depression and memory impairments. Antidepressants have been used to prevent stress-induced abnormal pain sensation. Among various antidepressants, tianeptine has been reported to be able to prevent neurodegeneration due to chronic stress and reverse decreases in hippocampal volume. To assess the possible effect of tianeptine on FM symptoms, we constructed a FM animal model induced by restraint stress with intermittent cold stress. All mice underwent nociceptive assays using electronic von Frey anesthesiometer and Hargreaves equipment. To assess the relationship between tianeptine and expression levels of brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and phosphorylated cAMP response element-binding protein (p-CREB), western blotting and immunohistochemistry analyses were performed. In behavioral analysis, nociception tests showed that pain threshold was significantly decreased in the FM group compared to that in the control group. Western blot and immunohistochemical analyses of medial prefrontal cortex (mPFC) and hippocampus showed downregulation of BDNF and p-CREB proteins in the FM group compared to the control group. However, tianeptine recovered these changes in behavioral tests and protein level. Therefore, this FM animal model might be useful for investigating mechanisms linking BDNF-CREB pathway and pain. Our results suggest that tianeptine might potentially have therapeutic efficacy for FM.
Animals* ; Antidepressive Agents ; Behavior Rating Scale ; Blotting, Western ; Brain-Derived Neurotrophic Factor* ; Cyclic AMP Response Element-Binding Protein ; Depression ; Down-Regulation ; Fibromyalgia* ; Hippocampus ; Immunohistochemistry ; Memory ; Mice ; Models, Animal* ; Pain Measurement ; Pain Threshold ; Prefrontal Cortex ; Risk Factors ; Sensation ; Stress, Psychological

PURPOSE: Severe sepsis is associated with functional disability among patients surviving an acute phase of infection. Efforts to improve functional impairment are important. We assessed the effects of early exercise rehabilitation on functional outcomes in patients with severe sepsis. MATERIALS AND METHODS: A prospective, single-center, case-control study was conducted between January 2013 and May 2014 at a tertiary care center in Korea. Patients with severe sepsis and septic shock were enrolled and randomized to receive standard sepsis treatment or intervention. Intervention involved early targeted physical rehabilitation with sepsis treatment during hospitalization. Participants were assessed at enrollment, hospital discharge, and 6 months after enrollment. Functional recovery was measured using the Modified Barthel Index (MBI), Functional Independence Measure (FIM), and Instrumental Activities of Daily Living (IADL). RESULTS: Forty participants (21 intervention patients) were included in an intention-to-treat analysis. There were no significant differences in baseline MBI, FIM, and IADL between groups. Intervention yielded greater improvement of MBI, FIM, and IADL in the intervention group at hospital discharge, but not significantly. Subgroup analysis of patients with APACHE II scores ≥10 showed significantly greater improvement of physical function at hospital discharge (MBI and FIM) in the intervention group, compared to the control group (55.13 vs. 31.75, p=0.048; 52.40 vs. 31.25, p=0.045). Intervention was significantly associated with improvement of MBI in multiple linear regression analysis (standardized coefficient 0.358, p=0.048). CONCLUSION: Early physical rehabilitation may improve functional recovery at hospital discharge, especially in patients with high initial severity scores.
Activities of Daily Living ; APACHE ; Case-Control Studies ; Hospitalization ; Humans ; Korea ; Linear Models ; Prospective Studies ; Rehabilitation* ; Sepsis* ; Shock, Septic ; Tertiary Care Centers