Abstract
The drug treatment for neuropathic pain remains a challenge due to poor efficacy and patient satisfaction. Curcumin has been reported to alleviate neuropathic pain, but its clinical application is hindered by its low solubility and poor oral bioavailability. Curcumin diglutaric acid (CurDG) is a curcumin prodrug with improved water solubility and in vivo antinociceptive effects. In this study, we investigated the anti-inflammatory mechanisms underlying the analgesic effect of CurDG in the chronic constriction injury (CCI)-induced neuropathy mouse model. Repeated oral administration of CurDG at a low dose equivalent to 25 mg/kg/day produced a significant analgesic effect in this model, both anti-allodynic activity and anti-hyperalgesic activity appearing at day 3 and persisting until day 14 post-CCI surgery (p < 0.001) while having no significant effect on the motor performance. Moreover, the repeated administration of CurDG diminished the increased levels of the pro-inflammatory cytokines: TNF-α and IL-6 in the sciatic nerve and the spinal cord at the lowest tested dose (equimolar to 25 mg/kg curcumin). This study provided pre-clinical evidence to substantiate the potential of pursuing the development of CurDG as an analgesic agent for the treatment of neuropathic pain.
Highlights
Neuropathic pain is characterized by abnormal signaling of pain pathways arising from injury or malfunction in the central or peripheral nervous systems [1]
Our preliminary studies showed that Curcumin diglutaric acid (CurDG) exhibited higher anti-nociceptive activity in the hot-plate analgesia test in mice compared to curcumin
We investigated the anti-inflammatory mechanisms underlying the analgesic effects of CurDG in the chronic constriction injury (CCI) of sciatic nerve-induced neuropathy in mice (Figure 1B)
Summary
Neuropathic pain is characterized by abnormal signaling of pain pathways arising from injury or malfunction in the central or peripheral nervous systems [1]. Major symptoms of neuropathic pain include hyperalgesia, allodynia, and spontaneous pain. Hyperalgesia and allodynia are the elevated sensitivity to painful and non-painful stimuli, respectively. Since prolonged neuropathic pain leads to major suffering, lower quality of life, and disability, it is considered as a major factor contributing to the global burden of disease. Current pharmacotherapy for neuropathic pain includes tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, calcium channel α-2-δ ligands, and opioids. The complexity of this disease and the side effects and low efficacy in pain relief associated with the currently available pharmacological agents create an opportunity to develop effective treatments to relieve neuropathic pain [2,3]
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