Short-term high-fat diet aggravates postoperative pain via peripheral S1PR3

Abstract

Postoperative pain and obesity are common problems worldwide. Both preclinical and clinical studies have suggested that obesity might act as a risk factor for poorly controlled postoperative pain. Unfortunately, the precise mechanism of how high-fat diet affects postoperative pain remains largely unknown. In this study, behavioral tests including von Frey tests, Hargreaves tests and temperature preference tests have confirmed that short-term high-fat diet exacerbates and prolongs acute postoperative pain. Quantitative PCR and Western Blots have revealed that S1PR3 is upregulated in injured mice fed with high-fat diet, along with COX2 and phosphorylated Akt. By using an S1PR3 antagonist FTY720, both the behavioral and molecular effects of highfat diet were reversed. Additionally, flow cytometry suggests that high-fat diet increases local infiltration of macrophages and immunofluorescence studies suggest that S1PR3 colocalizes with epidermal Langerhans cells in the hind paws. Therefore, we have identified S1PR3 as a potential link between high-fat diet and postoperative pain in the peripheral myeloid cells, ie not in the dorsal root ganglia or higher levels. Results from this study allow a deeper understanding of how high-fat diet exacerbates postoperative pain, yet the exact mechanism of how high-fat diet upregulates S1PR3 and how S1PR3 lead to increased nociception awaits further experiments.