eCM (Eur Cell Mater / e Cells & Materials) Not-for-profit Open Access
Created by Scientists, for Scientists
 ISSN:1473-2262         NLM:100973416 (link)         DOI:10.22203/eCM

2017   Volume No 33 – pages 279-293

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

Authors: L Xiao, M Ding, A Fernandez, P Zhao, L Jin, X Li

Address: Rm B051, Cobb Hall, Department of Orthopaedic Surgery, University of Virginia, 135 Hospital Dr. Charlottesville, VA 22908, USA

E-mail: xl2n at virginia.edu

Key Words: Curcumin, disc herniation, radiculopathy, neuroinflammation, oxidative stress, neuropathic pain, toxicity, nociceptive.

 

Publication date: May 9th 2017

Abstract: 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.

 

Article download: Pages 279-293 (PDF file)
DOI:
10.22203/eCM.v033a21

Supplementary video file (mov): SuppVid1
In our animal model, we punctured mouse lumbar disc from the far-lateral side and meanwhile exposed the nearby nerve root to mimic human disc herniation-induced pain. After surgery, curcumin was intraperitoneally injected every other day in group 1 (left), with the vehicle administered in group 2. At post-operation day 4, curcumin-treated mouse (left lane) was running quite swiftly with much stronger hind leg muscle and strength, compared to the vehicle group (right lane). This visually striking observation indicated animals were no longer in pain after curcumin treatment, which correlated with the quantitative von Frey mechanical test (Fig. 5).