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.

Objective: 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 weeks, followed by a hind paw incision. Four-week-old male mice were initially fed a CD or HFD for 8 weeks, then switched to the High or Low BCAA diet, and underwent a hind paw incision at 10 weeks of these diets. Pain behaviors were assessed. Several pro-inflammatory genes in the lumbar dorsal root ganglion (DRG) were detected by qPCR. Immunohistochemistry was used to estimate nerve fiber density at the incision site. Two-tailed unpaired Student's t-test, two-way repeated measures ANOVA with Bonferroni posttests, and one-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 pro-inflammatory responses in the DRG and the reduction of nerve fiber density near the incision site on day 3 post-surgery (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 non-pharmacological therapeutic to relieve pain in individuals on a conventional high-fat diet.