Augmented Pain and Inflammation with Obesity: A Role for the Pro-Inflammatory Cytokine Visfatin

Abstract

Obesity is associated with several co-morbidities including chronic pain. Systemic low-grade chronic inflammation and dysregulation of pro-inflammatory cytokines have been proposed to underlie these phenomena. This study characterized pain and inflammation, and levels of the pro-inflammatory cytokine visfatin, in a rodent model of obesity, and investigated whether treatment with the visfatin inhibitor, FK866, has anti-inflammatory and/or analgesic effects in normal and obese rats. The effects of pre-administration of FK866 (3, 10 mg/kg; i.p.) on carrageenan (3%; i.d. into the left paw)-induced thermal and mechanical hypersensitivity and paw oedema was measured in adult male Wistar rats fed a normal diet (ND) or high fat diet (HFD) for 12 weeks. HFD-fed rats displayed an increased sensitivity to acute mechanical nociceptive stimulation, and potentiated mechanical hyperalgesia and peripheral inflammation to carrageenan. Levels of circulating visfatin were increased in HFD-fed rats. Treatment with FK866, a visfatin inhibitor, was effective in reducing carrageenan-induced hyperalgesia and paw oedema in both ND-fed and HFD-fed rats. These data show that FK866 has anti-inflammatory and analgesic properties. The potentiated response to pain and inflammation, and elevated visfatin levels in HFD-fed rats supports the hypothesis that obesity is a chronic low-grade inflammatory disorder. Reversal of this co-morbidity by blocking visfatin may be a novel therapeutic strategy for managing pain with obesity.