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

// Ying Xu 1, 2 , Dan Lin 1 , Xuefeng Yu 1 , Xupei Xie 1 , Liqun Wang 3 , Lejing Lian 1 , Ning Fei 1 , Jie Chen 1 , Naping Zhu 1 , Gang Wang 4 , Xianfeng Huang 3 , Jianchun Pan 1 1 Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province, 325021, China 2 Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA 3 Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou, Jiangsu Province, 213000, China 4 Department of Clinical Pharmacy, Hangzhou First People’s Hospital, Hangzhou, Zhejiang Province, 310006, China Correspondence to: Jianchun Pan, e-mail: wenzhoupan2003@163.com Keywords: ferulic acid, neuropathic pain, analgesic effect, monoamine, opioid receptor Received: November 22, 2015      Accepted: February 11, 2016      Published: March 07, 2016 ABSTRACT 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.