Research Papers:

The antinociceptive effects of ferulic acid on neuropathic pain: involvement of descending monoaminergic system and opioid receptors

Ying Xu, Dan Lin, Xuefeng Yu, Xupei Xie, Liqun Wang, Lejing Lian, Ning Fei, Jie Chen, Naping Zhu, Gang Wang, Xianfeng Huang and Jianchun Pan _

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Oncotarget. 2016; 7:20455-20468. https://doi.org/10.18632/oncotarget.7973

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Ying Xu1,2, Dan Lin1, Xuefeng Yu1, Xupei Xie1, Liqun Wang3, Lejing Lian1, Ning Fei1, Jie Chen1, Naping Zhu1, Gang Wang4, Xianfeng Huang3, Jianchun Pan1

1Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province, 325021, China

2Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA

3Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou, Jiangsu Province, 213000, China

4Department of Clinical Pharmacy, Hangzhou First People’s Hospital, Hangzhou, Zhejiang Province, 310006, China

Correspondence to:

Jianchun Pan, e-mail: [email protected]

Keywords: ferulic acid, neuropathic pain, analgesic effect, monoamine, opioid receptor

Received: November 22, 2015     Accepted: February 11, 2016     Published: March 07, 2016


Neuropathic pain can be considered as a form of chronic stress that may share common neuropathological mechanism between pain and stress-related depression and respond to similar treatment. Ferulic acid (FA) is a major active component of angelica sinensis and has been reported to exert antidepressant-like effects; however, it remains unknown whether FA ameliorate chronic constriction injury (CCI)-induced neuropathic pain and the involvement of descending monoaminergic system and opioid receptors. Chronic treatment with FA (20, 40 and 80 mg/kg) ameliorated mechanical allodynia and thermal hyperalgesia in von Frey hair and hot plate tasks, accompanied by increasing spinal noradrenaline (NA) and serotonin (5-HT) levels. Subsequent study suggested that treatment of CCI animals with 40 and 80 mg/kg FA also inhibited spinal MAO-A levels. FA’s effects on mechanical allodynia or thermal hyperalgesiawas blocked by 6-hydroxydopamine (6-OHDA) or p-chlorophenylalanine (PCPA) via pharmacological depletion of spinal noradrenaline or serotonin. Moreover, the anti-allodynic action of FA on mechanical stimuli was prevented by pre-treatment with beta2-adrenoceptor antagonist ICI 118,551, or by the delta-opioid receptor antagonist naltrindole. While the anti-hyperalgesia on thermal stimuli induced by FA was blocked by pre-treatment with 5-HT1A receptor antagonist WAY-100635, or with the irreversible mu-opioid receptor antagonist beta-funaltrexamine. These results suggest that the effect of FA on neuropathic pain is potentially mediated via amelioration of the descending monoaminergic system that coupled with spinal beta2- and 5-HT1A receptors and the downstream delta- and mu-opioid receptors differentially.

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