Effects of curcumin on TTX-R sodium currents of dorsal root ganglion neurons in type 2 diabetic rats with diabetic neuropathic pain

Meng, Bo; Shen, Lanxiao; Shi, Xiaoting; Gong, Yongsheng; Fan, Xiaofang; Li, Jun; Cao, Hong

doi:10.1016/j.neulet.2015.08.011

Cited by 19 publications

(11 citation statements)

References 23 publications

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“…For instance, studies suggested that curcumin could inhibit H3 and H4 acetylation in DRG, downregulate mGlu2 receptors in the spinal cord (Zammataro et al ., 2014) and ameliorate CX3CR1 expression through the activation of NF-κB p65 in spinal cord and DRG of a CCI rat model (Cao et al ., 2014). Moreover, curcumin decreases the expression of pERK, pJNK and pNR1 activated by nerve ligation (Jeon et al ., 2013) and attenuates TTX-R sodium currents of small-sized DRG neurons isolated from diabetic neuropathic pain rats (Meng et al ., 2015). In addition, a histological study of nerve crush model, using stereological methods, revealed that curcumin restored and protected mean cell volume, total volume (A- and B-cells) and total surface of DRG cells, total number, diameter and area of the myelinated nerve fibres (Noorafshan et al ., 2011a; Noorafshan et al ., 2011b).…”

Section: Discussionmentioning

confidence: 99%

“…Although the aetiology of neuropathic pain has not reached a common consensus, the intricate link between TNF-α and neuro-inflammatory signalling systems has drawn attention in the development of drugs to resolve the neuropathic pain (Leung and Cahill, 2010). In this perspective, systemic administration of curcumin has been shown to effectively alleviate neuropathic pain in several animal models, such as chronic constrictive injury (Zammataro et al ., 2014) and diabetic neuropathic pain (Meng et al ., 2015). Our study, performed monitoring the animal behaviour for up to two weeks after surgery, suggested that curcumin significantly attenuated ipsilateral mechanical hyperalgesia caused by disc herniation (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Studies, covering a treatment period of three months, have shown that curcumin does not possess acute toxicity at doses of 2 g/kg of body weight in mice and 8,000 mg/day in humans (Chainani-Wu, 2003; JS, 2009). In addition to its anti-inflammatory effect, curcumin has demonstrated an analgesic effect in several animal models of neuropathic pain, such as pain in diabetes (Meng et al ., 2015) and chronic constrictive injury of spinal cord (Jeon et al ., 2013; Noorafshan et al ., 2011a). Curcumin has been reported to act on multiple cellular targets and signalling pathways suppressing production of mediators of inflammation and neuronal apoptosis, including toll-like receptors and nuclear factor-κB (Rahimifard et al ., 2017), growth factors, inflammatory cytokines and protein kinases (Zhou et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Curcumin alleviates lumbar radiculopathy by reducing neuroinflammation, oxidative stress and nociceptive factors

Xiao¹,

Ding²,

Fernandez³

et al. 2017

eCM

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Current non-surgical treatments for lumbar radiculopathy [e.g. epidural steroids and Tumour necrosis factor-α (TNF-α) antagonists] are neither effective nor safe. As a non-toxic natural product, curcumin possesses an exceptional anti-inflammatory profile. We hypothesised that curcumin alleviates lumbar radiculopathy by attenuating neuroinflammation, oxidative stress and nociceptive factors. In a dorsal root ganglion (DRG) culture, curcumin effectively inhibited TNF-α-induced neuroinflammation, in a dose-dependent manner, as shown by mRNA and protein expression of IL-6 and COX-2. Such effects might be mediated via protein kinase B (AKT) and extracellular signal regulated kinase (ERK) pathways. Also, a similar effect in combating TNF-α-induced neuroinflammation was observed in isolated primary neurons. In addition, curcumin protected neurons from TNF-α-triggered excessive reactive oxygen species (ROS) production and cellular apoptosis and, accordingly, promoted mRNA expression of the anti-oxidative enzymes haem oxygenase-1, catalase and superoxide dismutase-2. Intriguingly, electronic von Frey test suggested that intraperitoneal injection of curcumin significantly abolished ipsilateral hyperalgesia secondary to disc herniation in mice, for up to 2 weeks post-surgery. Such in vivo pain alleviation could be attributed to the suppression, observed in DRG explant culture, of TNF-α-elicited neuropeptides, such as substance P and calcitonin gene-related peptide. Surprisingly, micro-computed tomography (µCT) data suggested that curcumin treatment could promote disc height recovery following disc herniation. Alcian blue/picrosirius red staining confirmed that systemic curcumin administration promoted regeneration of extracellular matrix proteins, visualised by presence of abundant newly-formed collagen and proteoglycan content in herniated disc. Our study provided pre-clinical evidence for expediting this natural, non-toxic pleiotropic agent to become a new and safe clinical treatment of radiculopathy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Curcumin alleviates lumbar radiculopathy by reducing neuroinflammation, oxidative stress and nociceptive factors

Xiao¹,

Ding²,

Fernandez³

et al. 2017

eCM

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“…These T2DM models were established, as previously described [ 11 , 12 ]. After 2 weeks of adaptive feeding, these rats were randomized into two groups: Con group and T2DM group.…”

Section: Methodsmentioning

confidence: 99%

Mechanism of the JAK2/STAT3-CAV-1-NR2B signaling pathway in painful diabetic neuropathy

et al. 2019

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Purpose The aim of the present study was to further elucidate the role of JAK2/STAT3-CAV-1-NR2B on painful diabetic neuropathy. Methods In vivo, the mechanical withdrawal threshold and thermal withdrawal latency were measured to evaluate neuropathic pain behaviors ( n = 8), while western blot ( n = 5) and an immunofluorescence double staining experiment ( n = 6) were performed to understand the molecular mechanism. In vitro, the individual culture of BV2 mouse microglia cell lines, the co-culture of BV2 mouse microglia cell lines and PC12 rat neuron cell lines, and western blot analysis were performed to understand the molecular mechanism between microglia and neurons. Results The expression of p-JAK2, p-STAT3, t-CAV-1, and p-NR2B was upregulated in the dorsal horn of DNP rats throughout the experiment. Through the immunofluorescence double staining experiment, it was found that p-STAT3 was mainly expressed in activated microglia, and this condition can be stably maintained for approximately 2 weeks after the establishment of the DNP model. The intrathecal injection of JAK2 inhibitor AG490 can relieve the abnormal expression of p-JAK2, p-STAT3, t-CAV-1, and p-NR2B, and relieve pain. The remission of AG490 began on the third day, and it could be stably sustained for 14 days. In vitro high-glucose induced the activation of p-STAT3 in microglia, thereby upregulating the expression of p-CAV-1 and p-NR2B in neurons in the co-culture system. JAK2 inhibitor AG490 can alleviate the abnormal expression of these proteins in the JAK2/STAT3-CAV-1-NR2B signaling pathway in vitro. Conclusions Microglial JAK2/STAT3 signaling probably contributes to neuropathic pain by activating the CAV-1-NR2B pathway.

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“…Voltage‐gated sodium channels are accountable for the rising phase of the membranes’ action potential in neurons as well as other excitable cells . Curcumin was able to improve diabetes mellitus and its complications such as diabetic neuropathic pain through voltage‐gated sodium channels and by increasing sodium content in dorsal root ganglion neurons .…”

Section: Introductionmentioning

confidence: 99%

Effects of curcumin on ion channels and pumps: A review

et al. 2019

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Curcumin, an orange‐yellow lipophilic polyphenolic molecule, is the active component of Curcuma longa, which is extensively used as a spice in most of the Asian countries. This natural compound is able to interact with a large number of molecular structures like proteins, enzymes, lipids, DNA, RNA, transporter molecules, and ion channels. It has been reported to possess several biological effects such as antioxidant, anti‐inflammatory, wound healing, antimicrobial, anticancer, antiangiogenic, antimutagenic, and antiplatelet aggregation properties. These beneficial effects of curcumin are because of its extraordinary chemical interactions such as extensive hydrogen and covalent bonding, metal chelation, and so on. Therefore, the aim of this review was to outline the evidence in which curcumin could affect different types of ion channels and ion channel‐related diseases, and also to elucidate basic molecular mechanisms behind it. © 2019 IUBMB Life, 2019

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Effects of curcumin on TTX-R sodium currents of dorsal root ganglion neurons in type 2 diabetic rats with diabetic neuropathic pain

Cited by 19 publications

References 23 publications

Curcumin alleviates lumbar radiculopathy by reducing neuroinflammation, oxidative stress and nociceptive factors

Curcumin alleviates lumbar radiculopathy by reducing neuroinflammation, oxidative stress and nociceptive factors

Mechanism of the JAK2/STAT3-CAV-1-NR2B signaling pathway in painful diabetic neuropathy

Effects of curcumin on ion channels and pumps: A review

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