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.
Highlights
Neuropathic pain is defined as pain arising as a direct consequence of a lesion or a disease affecting the somatosensory system [1]
While in the constriction injury (CCI) group, Ferulic acid (FA) treatment began on day 7 (i.e. 7 days after CCI, Figure 1B), the neuropathic mice exhibited remarkable thermal hyperalgesia and mechanical allodynia
Post-hoc analyses showed that FA at 80 mg/kg kept higher threshold both in mechanical allodynia and thermal hyperalgesia between 22–28 days after treatment (p < 0.001)
Summary
Neuropathic pain is defined as pain arising as a direct consequence of a lesion or a disease affecting the somatosensory system [1]. Patients with neuropathic pain have symptoms that are reflected by hypersensitivity to innocuous (allodynia) and noxious stimuli (hyperalgesia) [2] Available treatment, such as opioids and nonsteroid anti-inflammatory drugs, can produce serious side effects including drug tolerance and gastric ulcer [3, 4]. The complicated interactions between pain and depression indicate that multi-target therapy may contribute to treatment of neuropathic pain with improved efficacy and better therapeutic profiles. Phytochemicals are such agents that have multiple targets potential for ameliorating pain and the related emotional changes [6]. The underlying mechanism of analgesic effect of FA, i.e. the roles of spinal monoamines, the adrenoceptors and serotonin receptors in regulation of descending inhibitory pathways, remains unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
