High-fat diet increases pain behaviors in rats with or without obesity.

Obesity is associated with increased risk for chronic pain. Basic mechanisms for this association are poorly understood. Using a milder version of a radicular pain model, local inflammation of the dorsal root ganglion (DRG), we observed marked increases in mechanical and cold allodynia in rats of both sexes that were maintained on a high-fat diet (HFD) for 6 weeks prior to DRG inflammation. Notably, this increase in pain-related behaviors occurred in both Long-Evans and Sprague-Dawley rats despite the fact that the 6-week HFD exposure induced obesity (e.g., increased insulin, leptin, weight, and percent body fat) in the Long-Evans, but not Sprague-Dawley, strains. This suggested that HFD, rather than obesity per se, increased pain behaviors. Increased pain behaviors were observed even after a much shorter (1 week) exposure to the HFD but the effect was smaller. HFD also increased behavioral responses and paw swelling to paw injection of complete Freund's adjuvant, a model of peripheral inflammatory pain. No change was detected in plasma cytokine levels in HFD rats. However, increased macrophage infiltration of the DRG was observed in response to the HFD, absent any pain model. The results suggest that HFD can increase pain even when it does not cause obesity.