Ferulic Acid Alleviates Neuropathic Pain: Involvement of Descending Monoaminergic System and Opioid Receptors

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. FA is a major active component of angelica sinensis and has been reported to exert antidepressant‐like effects; however, it remains unknown whether resveratrol ameliorate CCI‐induced neuropathic pain. Chronic treatment with FA (10, 20, 40 and 80 mg/kg) twice daily for 3 weeks ameliorated mechanical allodynia and thermal hyperalgesia in von Frey hair and hot plate tasks, accompanied by increasing spinal monoamine levels. Pharmacological depletion of spinal noradrenaline (NA) or serotonin (5‐HT) by 6‐hydroxydopamine (6‐OHDA) or p‐chlorophenylalanine (PCPA) completely blocked FA's effects on mechanical allodynia or thermal hyperalgesia, respectively. The anti‐allodynic action of FA on mechanical stimuli was prevented by co‐treatment with beta2‐adrenoceptor antagonist ICI 118,551, or by co‐treatment with delta‐opioid receptor antagonist naltrindole. Moreover, the anti‐hyperalgesia on thermal stimuli induced by FA was blocked by co‐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 modulation of descending monoaminergic system that coupled with spinal b2‐ and 5‐HT1A receptors and the downstream opioid receptors.