Effects of a Standard American Diet and an anti-inflammatory diet in male and female mice.

BACKGROUND: Obesity and chronic pain are prevalent concerns. Pain is frequently experienced in weight-bearing joints, but is common in other areas of the body as well, suggesting other factors. Poor diet often contributes to obesity and can directly influence the immune system. We have shown that poor diet prolongs recovery from inflammatory injury. Therefore, our goal was to determine whether poor-quality diet-induced consequences could be prevented or reversed by an anti-inflammatory diet (AID). METHODS: A Standard American Diet (SAD) was developed to investigate the effects of poor diet on pain. The SAD includes amounts of refined sugar, carbohydrates and fats that better model the typical American diet, as compared to high-fat diets. We developed an AID to explore whether the effects of the SAD could reverse or whether the AID would enhance recovery prophylactically. The AID was developed using ingredients (epigallocatechin gallate, sulforaphane, resveratrol, curcumin and ginseng) with known anti-inflammatory properties. Following 15 weeks of diet [SAD, AID or regular (REG)] exposure, male and female mice underwent inflammatory injury, at which point some animals had their diets switched for the remainder of the study. RESULTS: Animals who consumed the SAD showed longer recovery compared to the AID- and REG-fed animals. Animals switched off the SAD had faster recovery times, with AID-fed animals recovering as fast as REG-fed animals. CONCLUSIONS: Poor diet prolonged recovery from inflammatory injury. Substitution of SAD with AID or REG promoted faster recovery. These findings suggest diet can be used as a non-pharmacological intervention following injury. SIGNIFICANCE: Obesity may increase susceptibility to chronic pain often due to poor diet. Diet has potential to be used as treatment for pain. This study investigates the use of a novel translatable diet to act as a preventative (i.e. prior to surgery) or an intervention (i.e. following an injury).

The Yin and Yang of pain: variability in formalin test nociception and morphine analgesia produced by the Yin Yang 1 transcription factor gene.

We recently observed a reliable phenotypic difference in the inflammatory pain sensitivity of a congenic mouse strain compared to its background strain. By constructing and testing subcongenic strains combined with gene-expression assays, we provide evidence for the candidacy of the Yy1 gene - encoding the ubiquitously expressed and multifunctional Yin Yang 1 transcription factor - as responsible. To confirm this hypothesis, we used a Cre/lox strategy to produce mutant mice in which Yy1 expression was ablated in Nav 1.8-positive neurons of the dorsal root ganglion. These mutants also displayed reduced inflammatory pain sensitivity on the formalin test. Further testing of pain-related phenotypes in these mutants revealed robustly increased sensitivity to systemic and spinal (but not supraspinal) morphine analgesia, and greatly increased endogenous (swim stress-induced) opioid analgesia. None of the known biological roles of Yin Yang 1 were suggestive of such a phenotype, and thus a novel player in pain modulatory systems has been identified.