Reducing Dietary Branched-Chain Amino Acids Intake Alleviates High-Fat Diet-Induced Pain Sensitization and Postoperative Pain in Male Mice

Abstract

Background

Poor dietary intake is associated with peripheral pain sensitization and postoperative pain. Given the limited research on diet and pain, it is essential to examine the possible analgesic effects of dietary interventions in preclinical studies.

Objectives

This study aimed to elucidate the role of high-fat diet (HFD) on pain sensitivity and postoperative pain, and determine the potential effects of modulating branched-chain amino acids (BCAA) intake on pain phenotypes.

Methods

Four-week-old male mice were fed a purified control diet (CD) or HFD for 10 wk, followed by a hind paw incision. Four-week-old male mice were initially fed a CD or HFD for 8 wk, then switched to the high or low BCAA diet, and underwent a hind paw incision at 10 wk of these diets. Pain behaviors were assessed. Several proinflammatory genes in the lumbar dorsal root ganglion (DRG) were detected by quantitative polymerase chain reaction. Immunohistochemistry was used to estimate nerve fiber density at the incision site. Two-tailed unpaired Student’s t-test, 2-way repeated-measures analysis of variance (ANOVA) with Bonferroni posttests, and 1-way ANOVA with Tukey’s multiple comparisons test were used for data analysis.

Results

HFD consumption induced pain sensitization and worsened postoperative pain in male mice (P < 0.0001). In CD group, mice switching to high or low BCAA diet displayed minor impacts on pain phenotypes. In HFD mice, switching to high BCAA diet exacerbated hyperalgesia and postsurgical pain (P < 0.05), leading to proinflammatory responses in the DRG and the reduction of nerve fiber density near the incision site on day 3 postsurgery (P < 0.05); whereas low BCAA diet intake alleviated these effects (P < 0.05).

Conclusions

High BCAA intake has negative impacts on pain sensitivity and postoperative pain in HFD-fed mice. Reducing dietary BCAA may be a novel nonpharmacological therapeutic to relieve pain in individuals on a conventional HFD.