Lycopene ameliorates neuropathic pain by upregulating spinal astrocytic connexin 43 expression

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• 作者：Fang Fang Zhang ; Norimitsu Morioka ; ^{mnori@hiroshima-u.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Tomoya Kitamura ; Shiori Fujii ; Kazuki Miyauchi ; Yoki Nakamura ; Kazue Hisaoka-Nakashima ; Yoshihiro Nakata
• 关键词：Cx43 ; connexin43 ; DMEM ; Dulbecco's modified Eagle's medium ; GAPDH ; glyceraldehydes-3-phosphate dehydrogenase ; NAC ; N-acetyl cysteine ; PSNL ; partial sciatic nerve ligation ; RAR ; retinoic acid receptor ; RARE ; retinoic acid response element ; TNF ; tumor necrosis factor
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：15 June 2016
• 年：2016
• 卷：155
• 期：Complete
• 页码：116-122
• 全文大小：657 K

文摘

Peripheral nerve injury upregulates tumor necrosis factor (TNF) expression. In turn, connexin 43 (Cx43) expression in spinal astrocytes is downregulated by TNF. Therefore, restoration of spinal astrocyte Cx43 expression to normal level could lead to the reduction of nerve injury-induced pain. While the non-provitaminic carotenoid lycopene reverses thermal hyperalgesia in mice with painful diabetic neuropathy, the antinociceptive mechanism is not entirely clear. The current study evaluated whether the antinociceptive effect of lycopene is mediated through the modulation of Cx43 expression in spinal astrocytes.

Main methods

The effect of lycopene on Cx43 expression was examined in cultured rat spinal astrocytes. The effect of intrathecal lycopene on Cx43 expression and neuropathic pain were evaluated in mice with partial sciatic nerve ligation (PSNL).

Key findings

Treatment of cultured rat spinal astrocytes with lycopene reversed TNF-induced downregulation of Cx43 protein expression through a transcription-independent mechanism. By contrast, treatment of cultured spinal astrocytes with either pro-vitamin A carotenoid β-carotene or antioxidant N-acetyl cysteine had no effect on TNF-induced downregulation of Cx43 protein expression. In addition, repeated, but not single, intrathecal treatment with lycopene of mice with a partial sciatic nerve ligation significantly prevented not only the downregulation of Cx43 expression in spinal dorsal horn but mechanical hypersensitivity as well.

Significance

The current findings suggest a significant spinal mechanism that mediates the analgesic effect of lycopene, through the restoration of normal spinal Cx43 expression.