Limonene reduces hyperalgesia induced by gp120 and cytokines by modulation of IL-1 β and protein expression in spinal cord of mice

Aims: We have investigated the antihyperalgesic effects of limonene in mice that received intrathecal injection of gp120. Main methods: Male Swiss mice received gp120, IL-1 beta or TNF-alpha intrathecally or sterile saline as a control. A mechanical sensitivity test was performed at 2 and 3 h after the injection. Spinal cord and blood samples were isolated for protein quantification. Key findings: Intrathecal administration of gp120 increased mechanical sensitivity measured with an electronic Von Frey apparatus, at 2 and 3 h after the injections. Limonene administered orally prior to gp120 administration significantly decreased this mechanical sensitivity at 3 h after the gp120 injection. In addition, intrathecal injection of gp120 increased IL-1 beta and IL-10 in serum, and limonene prevented the ability of gp120 to increase these cytokines. Limonene also inhibited TNF-alpha and IL-1 beta-induced mechanical hyperalgesia. Western blot assay demonstrated limonene was capable of increasing SOD expression in the cytoplasm of cells from spinal cord at 4 h after intrathecal IL-1 beta injection. Significance: These results demonstrate that gp120 causes mechanical hyperalgesia and a peripheral increase in IL-1 beta and IL-10, and that prior administration of limonene inhibits these changes. Also limonene modulates the activation of SOD expression in the spinal cord after spinal IL-1 beta application. The ability of limonene to inhibit the mechanical hyperalgesia induced by gp120, TNF-alpha and IL-1 beta emphasizes the anti-inflammatory action of limonene, specifically its ability to inhibit cytokine production and its consequences. (C) 2016 Published by Elsevier Inc.