Interleukin‐1β (IL‐1β) increases pain behavior and the blood glucose level: Possible involvement of sympathetic nervous system

The relationship between interleukin-1β (IL‐1β)‐induced nociception and the blood glucose level was studied in ICR mice. We found in the present study that intrathecal (i.t.) injection of IL‐1β increased pain behavior. In addition, i.t. IL‐1β injection caused an elevation of the blood glucose level. The time‐course study showed that maximal blood glucose level was observed 30 and 60min after i.t. IL‐1β administration. Furthermore, i.t. injection of IL‐1β enhanced the blood glucose level when mice were orally fed with d‐glucose. The i.t. administration of IL‐1β antagonist (AF12198) inhibited the hyperglycemia and pain behaviors induced by IL‐1β. We found in the present study that adrenal tyrosine hydroxylase (TH) mRNA level was also increased by i.t. IL‐1β injection. Furthermore, intraperitoneal (i.p.) pretreatment with phentolamine (an α1‐adrenergic blocker) or yohimbine (an α2‐adrenergic blocker) significantly attenuated the blood glucose level and pain behavior induced by IL‐1β administered i.t. However, the blood glucose level and pain behavior were not affected by butoxamine (a β2-adrenergic blocker), whereas metoprolol (a β2-adrenergic blocker) enhanced IL‐1β-induced blood glucose level and pain behavior in mice fed with d‐glucose. However, its effect was not statistically significant. Our results suggest that IL‐1β administered i.t. increases the blood glucose level via an activation of α adrenergic nervous system. ► The pain induced by intrathecally IL-1β administration increased blood glucose. ► TH mRNA level after i.t. IL-1β injection was enhanced in adrenal glands. ► The α–adrenergic blockers inhibited blood glucose and pain behavior induced by IL-1β. ► The blood glucose was not attenuated by β-adrenergic blockers. ► IL-1β injected i.t. increases blood glucose via activated sympathetic nervous system.