Antiallodynic and antihyperalgesic activities of zerumbone via the suppression of IL-1β, IL-6, and TNF-α in a mouse model of neuropathic pain

Figures & data

Figure 1 Chemical structure of zerumbone.

Figure 2 Changes in the body weights of mice in different treatment groups throughout the experimental period of 14 days.

Notes: Data are expressed as mean ± SEM; n=8 mice per group, assessed by two-way ANOVA followed by Bonferroni’s post hoc analysis. Filled circles indicate data significantly different (p≤0.05) from vehicle-treated group.
Abbreviations: ANOVA, analysis of variance; CCI, chronic constriction injury.

Figure 3 Effect of treatments on the (A) ipsilateral and (B) contralateral paw withdrawal thresholds toward mechanical allodynia as tested with von Frey filament test.

Notes: Data are expressed as mean ± SEM; n=8 mice per group, assessed by two-way ANOVA followed by Bonferroni’s post hoc analysis. Filled circles indicate data significantly different (p≤0.05) from vehicle-treated group.
Abbreviation: ANOVA, analysis of variance.

Figure 4 Effect of treatments on cold allodynia withdrawal response as tested with cold plate.

Notes: Data are expressed as mean ± SEM; n=8 mice per group, assessed by two-way ANOVA followed by Bonferroni’s post hoc analysis. Filled circles indicate data significantly different (p≤0.05) from vehicle-treated group.
Abbreviation: ANOVA, analysis of variance.

Figure 5 Effect of treatments on the (A) ipsilateral and (B) contralateral paw withdrawal latency toward thermal hyperalgesia as tested with Hargreaves.

Notes: Data are expressed as mean ± SEM; n=8 mice per group, assessed by two-way ANOVA followed by Bonferroni’s post hoc analysis. Filled circles indicate data significantly different (p≤0.05) from vehicle-treated group.
Abbreviation: ANOVA, analysis of variance.

Figure 6 Effect of treatments on the (A) ipsilateral and (B) contralateral paw withdrawal threshold toward mechanical hyperalgesia as tested with Randall–Selitto in CCI and sham mice.

Notes: Data are expressed as mean ± SEM; n=8 mice per group, assessed by two-way ANOVA followed by Bonferroni’s post hoc analysis. Filled circles indicate data significantly different (p≤0.05) from vehicle-treated group.
Abbreviations: ANOVA, analysis of variance; CCI, chronic constriction injury.

Figure 7 Effect of the treatments on the rotarod performance in CCI and sham mice.

Notes: Data are mean ± SEM; n=8 mice per group.
Abbreviation: CCI, chronic constriction injury.

Figure 8 Effect of zerumbone (10 and 50 mg/kg) treatments on the blood plasma levels of (A) IL-1β, (B) TNF-α, (C) IL-10, and (D) IL-6 in CCI and sham mice.

Notes: Values represent mean ± SEM; n=6 mice per group. ^a.b.cColumns with different superscripts are significantly different at p≤0.05.
Abbreviations: CCI, chronic constriction injury; IL-1β, interleukin-1beta; TNF-α, tumor necrosis factor-alpha.

Figure 9 Effect of zerumbone (10 and 50 mg/kg) treatment on the L4–L6 spinal cord levels of (A) IL-1β, (B) TNF-α, (C) IL-10, and (D) IL-6 in CCI and sham mice.

Notes: Values represent mean ± SEM; n=6 mice per group. ^a.b.cColumns with different superscripts are significantly different at p≤0.05.
Abbreviations: CCI, chronic constriction injury; IL-1β, interleukin-1beta; TNF-α, tumor necrosis factor-alpha.

Figure 10 Overview of the antiinflammatory actions of zerumbone on neuropathic pain symptoms allodynia and hyperalgesia.

Notes: (A) In an event of nerve injury, resident and blood-borne macrophages and mast cells rush to the site of injury. These cells release inflammatory mediators such as IL-1β, TNF-α, and IL-6. These mediators cause heightened sensitivity at nociceptor terminals and dorsal horn of spinal cord (red box) leading to behavioral symptoms such as allodynia and hyperalgesia. (B) Treatment of zerumbone lowers the levels of inflammatory mediators (IL-1β, TNF-α, and IL-6) in the blood and spinal cord. This prevents hypersensitivity at nociceptor terminals and dorsal horn of spinal cord (red box) resulting in the attenuation of allodynia and hyperalgesia.
Abbreviations: IL, interleukin; IL-1β, interleukin-1beta; TNF-α, tumor necrosis factor-alpha.