Abstract
The management of neuropathic pain is still a major challenge because of its unresponsiveness to most common treatments. Curcumin has been reported to play an active role in the treatment of various neurological disorders, such as neuropathic pain. Curcumin has long been recognized as a p300/CREB-binding protein (CBP) inhibitor of histone acetyltransferase (HAT) activity. However, this mechanism has never been investigated for the treatment of neuropathic pain with curcumin. The aim of the present study was to investigate the anti-nociceptive role of curcumin in the chronic constriction injury (CCI) rat model of neuropathic pain. Furthermore, with this model we investigated the effect of curcumin on P300/CBP HAT activity-regulated release of the pro-nociceptive molecules, brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (Cox-2). Treatment with 40 and 60 mg/kg body weight curcumin for 7 consecutive days significantly attenuated CCI-induced thermal hyperalgesia and mechanical allodynia, whereas 20 mg/kg curcumin showed no significant analgesic effect. Chromatin immunoprecipitation analysis revealed that curcumin dose-dependently reduced the recruitment of p300/CBP and acetyl-Histone H3/acetyl-Histone H4 to the promoter of BDNF and Cox-2 genes. A similar dose-dependent decrease of BDNF and Cox-2 in the spinal cord was also observed after curcumin treatment. These results indicated that curcumin exerted a therapeutic role in neuropathic pain by down-regulating p300/CBP HAT activity-mediated gene expression of BDNF and Cox-2.
Highlights
Neuropathic pain is caused by a lesion or disease affecting the nervous systems, and is generally manifested as spontaneous pain, hyperalgesia, and allodynia [1,2]
Curcumin attenuated thermal hyperalgesia and mechanical allodynia in constriction injury (CCI) rats Neuropathic pain in rats can be examined by measuring the paw withdrawal latency or threshold to thermal or mechanical stimulation, respectively [24,35]
Findings of the present study indicated that the anti-nociceptive effect of curcumin on neuropathic pain resulted from peripheral nerve injury
Summary
Neuropathic pain is caused by a lesion or disease affecting the nervous systems, and is generally manifested as spontaneous pain, hyperalgesia, and allodynia [1,2]. Curcuma longa (tumeric) is a rhizomatous herbaceous perennial plant of the ginger family. It is commonly found in traditional Chinese medicine, such as in Xiaoyao-san, and is used to treat symptoms of mental stress, hypochondriac pain, and mania. 1, 7bis (4-hydroxy-3-methoxyphenyl)-1, 6-heptadiene-3, 5-dione (curcumin) is the main ingredient of curcuma longa, and has a variety of effects, such as anti-oxidative, anti-inflammatory, immunomodulatory, and neuro-protective [6,7]. Curcumin has neuroprotective effects in various neurological disorders, such as Alzheimer’s disease [8], tardive dyskinesia [9], major depression [10], and diabetic neuropathy [11,12].
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