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The soluble epoxide hydrolase inhibitor TPPU improves comorbidity of chronic pain and depression via the AHR and TSPO signaling
- Source :
- Journal of translational medicine, vol 21, iss 1
- Publication Year :
- 2023
- Publisher :
- Springer Science and Business Media LLC, 2023.
-
Abstract
- Background Patients suffering from chronic pain often also exhibit depression symptoms. Soluble epoxide hydrolase (sEH) inhibitors can decrease blood levels of inflammatory cytokines. However, whether inhibiting sEH signaling is beneficial for the comorbidity of pain and depression is unknown. Methods According to a sucrose preference test (SPT), spared nerve injury (SNI) mice were classified into pain with or without an anhedonia phenotype. Then, sEH protein expression and inflammatory cytokines were assessed in selected tissues. Furthermore, we used sEH inhibitor TPPU to determine the role of sEH in chronic pain and depression. Importantly, agonists and antagonists of aryl hydrocarbon receptor (AHR) and translocator protein (TSPO) were used to explore the pathogenesis of sEH signaling. Results In anhedonia-susceptible mice, the tissue levels of sEH were significantly increased in the medial prefrontal cortex (mPFC), hippocampus, spinal cord, liver, kidney, and gut. Importantly, serum CYP1A1 and inflammatory cytokines, such as interleukin 1β (IL-1β) and the tumor necrosis factor α (TNF-α), were increased simultaneously. TPPU improved the scores of mechanical withdrawal threshold (MWT) and SPT, and decreased the levels of serum CYP1A1 and inflammatory cytokines. AHR antagonist relieved the anhedonia behaviors but not the algesia behaviors in anhedonia-susceptible mice, whereas an AHR agonist abolished the antidepressant-like effect of TPPU. In addition, a TSPO agonist exerted a similar therapeutic effect to that of TPPU, whereas pretreatment with a TSPO antagonist abolished the antidepressant-like and analgesic effects of TPPU. Conclusions sEH underlies the mechanisms of the comorbidity of chronic pain and depression and that TPPU exerts a beneficial effect on anhedonia behaviors in a pain model via AHR and TSPO signaling.
- Subjects :
- Anhedonia
Cytoplasmic and Nuclear
Immunology
Chronic pain
Comorbidity
Medical and Health Sciences
General Biochemistry, Genetics and Molecular Biology
Mice
Receptors
Behavioral and Social Science
Cytochrome P-450 CYP1A1
Animals
2.1 Biological and endogenous factors
Aetiology
Aryl hydrocarbon receptor
Epoxide Hydrolases
Depression
Phenylurea Compounds
Pain Research
Neurosciences
General Medicine
Antidepressive Agents
Soluble epoxide hydrolase
Mental Health
TPPU
Aryl Hydrocarbon
Cytokines
Translocator protein
Subjects
Details
- ISSN :
- 14795876
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Journal of Translational Medicine
- Accession number :
- edsair.doi.dedup.....88f56b9cbf9ded1c83819ee06954448d