Metabolic Brain Disease

, Volume 28, Issue 4, pp 571–583 | Cite as

Ferulic acid increases pain threshold and ameliorates depression-like behaviors in reserpine-treated mice: behavioral and neurobiological analyses

  • Ying Xu
  • Lu Zhang
  • Tuo Shao
  • Lina Ruan
  • Lin Wang
  • Jiao Sun
  • Jianxin Li
  • Xinbo Zhu
  • James M. O’Donnell
  • Jianchun Pan
Original Paper


Depression-pain dyad involves a series of pathological changes including the dysfunction of neuroendocrine and immune networks. Depression and pain influence each other, but the mechanisms are still obscure. The present study aimed to investigate the effect of ferulic acid (FA) on reserpine-induced pain and depression-like behaviors in mice. The results showed that reserpine (1 mg/kg for 3 days, i.p.) led to a significant decrease in nociceptive threshold in thermal hyperalgesia and mechanical allodynia, as well as a significant increase in the immobility time in mouse models of despair test. The neurochemical assays suggested the decreased neurotransmitters (dopamine, norepinephrine and serotonin) along with the increased oxidative stress, inflammatory cytokines, and apoptotic parameters in the frontal cortex and hippocampus of the reserpinised mice. Treatment with FA (40 or 80 mg/kg, p.o.) reversed the behavioral abnormalities and decreased norepinephrine, serotonin and dopamine levels in the hippocampus and frontal cortex induced by reserpine. The higher dose of FA effectively antagonized the oxidative and nitrosative stress and inflammation as evidenced by down-regulated nitrite, LPO, IL-1β, TNF-α, and up-regulated GSH and SOD. Furthermore, FA produced a dose dependent decrease in substance P, NF-κβ p65 and caspase-3 levels in the frontal cortex and hippocampus of reserpinised mice. The findings suggest that FA exerts the effects on reserpine-induced pain and depression-like behaviors through regulating monoaminergic system, oxidative/antioxidant defense, inflammatory and apoptotic signaling pathways. Understanding the mechanism by which FA ameliorates depression and pain as a multi-targeted compound could open new avenues for the development of innovative treatments for depression coupled with pain.


Ferulic acid Depression-pain dyad Antidepressant effect Hyperalgesia Allodynia 



The authors do not have financial or personal conflicts of interest associated with this work. The project was sponsored by National Natural Science Foundation of China (No. 30901802), Wenzhou City Science & Technology Plan Item (No. Y20100201) Wenzhou Science and Technology Bureau Awards to Prof. J. C. Pan (No. Y20080097) and Ruian City Science & Technology Plan Item (No. 201002063). The authors thank Ms. Dorothy Redman for the suggestion that improve the quality of this manuscript.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ying Xu
    • 1
    • 2
  • Lu Zhang
    • 1
  • Tuo Shao
    • 1
  • Lina Ruan
    • 1
  • Lin Wang
    • 1
  • Jiao Sun
    • 1
  • Jianxin Li
    • 1
  • Xinbo Zhu
    • 1
  • James M. O’Donnell
    • 2
  • Jianchun Pan
    • 1
  1. 1.Institute of Experimental NeurobiologyWenzhou Medical CollegeWenzhouPeople’s Republic of China
  2. 2.Departments of Behavioral Medicine and Psychiatry and Neurobiology and AnatomyWest Virginia University Health Sciences CenterMorgantownUSA

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