Microbiota-Accessible Boron-Containing Compounds in Complex Regional Pain Syndrome

Abstract

The microbiota-gut-brain axis has garnered increasing attention in recent years for its role in various health conditions, including neuroinflammatory disorders like complex regional pain syndrome (CRPS). CRPS is a debilitating condition characterized by chronic neuropathic pain, and its etiology and pathophysiology remain elusive. Emerging research suggests that alterations in the gut microbiota composition and function could play a significant role in CRPS development and progression. Our paper explores the implications of microbiota in CRPS and the potential therapeutic role of boron (B). Studies have demonstrated that individuals with CRPS often exhibit dysbiosis, with imbalances in beneficial and pathogenic gut bacteria. Dysbiosis can lead to increased gut permeability and systemic inflammation, contributing to the chronic pain experienced in CRPS. B, an essential trace element, has shown promise in modulating the gut microbiome positively and exerting anti-inflammatory effects. Recent preclinical and clinical studies suggest that B supplementation may alleviate neuropathic pain and improve CRPS symptoms by restoring microbiota balance and reducing inflammation. Our review highlights the complex interplay between microbiota, inflammation, and neuropathic pain in CRPS and underscores the potential of B as a novel therapeutic approach to target the microbiota-gut-brain axis, offering hope for improved management of this challenging condition.

Keywords: boron-containing compounds; complex regional pain syndrome; gut–brain axis; gut–immune system axis; gut–musculoskeletal axis; microbiota; prebiotic boron.

Figure 1

AI-2 pathway: DPD easily cycles into R-DHMF and S-DHMF stereoisomers. R-DHMF and S-DHMF are solvated to establish S-THMF (AI-2 and AI-2B, two different types of AI-2 signal molecules in water). LuxP receptors connect the cyclic borated form (2S,4S-THMF-borate), and LsrB receptors connect the non-borated cyclic form (2R,4S-THMF). AI-2: Autoinducer-2; AI-2B: Autoinducer-2–furanosyl borate diester; DHMF: 2,4-Dihydroxy-2-methyldihydro-3-furanone; DPD: 4,5-Dihydroxy-2,3-pentanedione; THMF: 2-Methyl-2,3,3,4-tetrahydroxytetrahydrofuran. Scheme adapted from Ascenso et al. (2019) [129].

Figure 2

The proposed mechanism of action of prebiotic boron complex as a mediator for AI-2B and MuB production. AI-2: Autoinducer-2; AI-2B: Autoinducer-2–furanosyl borate diester; Glu: Monosaccharide (mainly fucose and sialic acid); GluB: Monosaccharide–boron complex; Mu: Mucin gel; MuB: Mucin gel–borate complex.

Figure 3

The synergy involving prebiotic boron, the microbiota–gut–immune system, and the microbiota–gut–musculoskeletal system is mediated via the microbiota–gut–organ axis.