Intrathecal curcumin attenuates pain hypersensitivity and decreases spinal neuroinflammation in rat model of monoarthritis.

Jun-Jie Chen,Lin-Xia Zhao,Lin Dai,Su Cao,Xiang Zhu,Yong-Jing Gao

doi:10.1038/srep10278

Abstract

Curcumin is a major component of turmeric and reportedly has anti-inflammatory and anti-oxidant effects. Neuroinflammation has been recognized to play an important role in the pathogenesis of various diseases in the central nervous system. Here we investigated the anti-nociceptive and anti-neuroinflammatory effect of curcumin on arthritic pain in rats. We found that repeated oral treatment with curcumin, either before or after complete Freund’s adjuvant (CFA) injection, dose-dependently attenuated CFA-induced mechanical allodynia and thermal hyperalgesia, but had no effect on joint edema. Repeated intrathecal injection of curcumin reversed CFA-induced pain hypersensitivity. Furthermore, such a curcumin treatment reduced CFA-induced activation of glial cells and production of inflammatory mediators [interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and monocyte inflammatory protein-1 (MIP-1α)] in the spinal cord. Curcumin also decreased lipopolysaccharide-induced production of IL-1β, tumor necrosis factor-α, MCP-1, and MIP-1α in cultured astrocytes and microglia. Our results suggest that intrathecal curcumin attenuates arthritic pain by inhibiting glial activation and the production of inflammatory mediators in the spinal cord, suggesting a new application of curcumin for the treatment of arthritic pain.

Highlights

(MIP-1α )] stimulated by lipopolysaccharide (LPS) in astrocytes, monocytes, or alveolar macrophages[12,13]
The expression of MIP-1α was increased at 1 day, 3 days and 10 days after Complete Freund’s adjuvant (CFA) injection (P < 0.05 or P < 0.01, or P < 0.001, vs. control, Fig. 4F). These results suggest that CFA-induced inflammatory pain is associated with activation of glial cells and the upregulation of proinflammatory cytokines and chemokines in the spinal cord
We investigated the anti-nociceptive and anti-neuroinflammatory effect of curcumin on CFA-induced pain hypersensitivity

Summary

Introduction

(MIP-1α )] stimulated by lipopolysaccharide (LPS) in astrocytes, monocytes, or alveolar macrophages[12,13]. In response to peripheral inflammation, glial cells (astrocytes and microglia) are activated and produce multiple inflammatory mediators such as proinflammatory cytokines and chemokines[19,22,23,24,25], which are involved in the regulation of synaptic transmission[26,27,28]. Inhibition of neuroinflammation that is mediated by glial cells attenuates inflammatory or neuropathic pain[19,20,21]. Whether curcumin can regulate the activity of glial cells and reduce the inflammation in the spinal cord in the setting of arthritic pain condition remains to be determined. We investigated the role of systemic or intrathecal treatment with curcumin on arthritic pain in the CFA-induced rat ankle joint monoarthritis (MA) model. We explored the possible analgesic mechanisms of spinal injection of curcumin by assaying the activation of spinal glial cells and the production of inflammatory mediators both in vivo and in vitro

Methods

Results

Conclusion