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The novel and potent anti-depressive action of triptolide and its influences on hippocampal neuroinflammation in a rat model of depression comorbidity of chronic pain
- Source :
- Brain, behavior, and immunity. 64
- Publication Year :
- 2016
-
Abstract
- Chronic pain and depression frequently coexist in clinical setting, and current clinical treatments for this comorbidity have shown limited efficacy. Triptolide (T10), an active component of Tripterygium wilfordii Hook F., has been demonstrated to exert strong analgesic activities in experimental pain models, but whether it possesses anti-depressive actions remains unknown. Using a depression comorbidity of chronic pain rat model induced by spinal nerve ligation (SNL), we investigated the potency of T10 for the treatment of comorbid depression in comparison with a widely used antidepressant, fluoxetine (FLX). Concomitant neuroinflammation changes were also examined in the hippocampus. The results showed that prophylactic and reversal treatments with T10 dose-dependently (30, 100, 300μg/kg) inhibited the depression-like behaviors (DLB) assessed by the forced swim test, sucrose preference test and body weight measurement. The anti-depressive efficacy of T10 at 300μg/kg was significantly stronger than that of FLX at 18mg/kg. T10 at all three doses exhibited more efficient analgesic effects than FLX at 18mg/kg. The combined application of T10 with FLX markedly augmented the effects of T10 or FLX per se, with the facilitating effects of T10 at 30μg/kg being most prominent. In addition, nerve injury caused the activation of microglia and p38 MAPK, the upregulation of IL-1β and TNF-α as well as the downregulation of IL-10 in the hippocampus at postoperative week (POW) 3. These neuroinflammatory responses were reversed by subchronic treatment with T10. Taken together, these results demonstrate that T10 possesses potent anti-depressive function, which is correlated with its immunoregulation in the hippocampus. The combination of a low dose of T10 with FLX may become a more effective medication strategy for the treatment of comorbid depression and chronic pain.
- Subjects :
- 0301 basic medicine
Male
Immunology
Analgesic
Pharmacology
Hippocampus
Rats, Sprague-Dawley
03 medical and health sciences
Behavioral Neuroscience
chemistry.chemical_compound
0302 clinical medicine
Fluoxetine
medicine
Animals
Neuroinflammation
Analgesics
Behavior, Animal
Dose-Response Relationship, Drug
Endocrine and Autonomic Systems
business.industry
Depression
Chronic pain
Triptolide
Nerve injury
Phenanthrenes
musculoskeletal system
medicine.disease
Antidepressive Agents
nervous system diseases
Disease Models, Animal
030104 developmental biology
chemistry
Hyperalgesia
Antidepressant
Encephalitis
Epoxy Compounds
Drug Therapy, Combination
Microglia
medicine.symptom
Chronic Pain
Diterpenes
Inflammation Mediators
business
030217 neurology & neurosurgery
Behavioural despair test
medicine.drug
Subjects
Details
- ISSN :
- 10902139
- Volume :
- 64
- Database :
- OpenAIRE
- Journal :
- Brain, behavior, and immunity
- Accession number :
- edsair.doi.dedup.....b666eab1e914bfa0c69c6fed8af55267