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-1β or TNF-α intrathecally or sterile saline as a control. A mechanical sensitivity test was performed at 2 and 3h 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 3h after the injections. Limonene administered orally prior to gp120 administration significantly decreased this mechanical sensitivity at 3h after the gp120 injection. In addition, intrathecal injection of gp120 increased IL-1β and IL-10 in serum, and limonene prevented the ability of gp120 to increase these cytokines. Limonene also inhibited TNF-α and IL-1β-induced mechanical hyperalgesia. Western blot assay demonstrated limonene was capable of increasing SOD expression in the cytoplasm of cells from spinal cord at 4h after intrathecal IL-1β injection.

Significance: These results demonstrate that gp120 causes mechanical hyperalgesia and a peripheral increase in IL-1β 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-1β application. The ability of limonene to inhibit the mechanical hyperalgesia induced by gp120, TNF-α and IL-1β emphasizes the anti-inflammatory action of limonene, specifically its ability to inhibit cytokine production and its consequences.