Tryptophan metabolism and small fibre neuropathy: a correlation study

Area of Science:

• Neuroscience
• Metabolomics
• Human Physiology

Background:

• Small nerve fibers in the epidermis detect pain, and their dysfunction leads to small fiber neuropathy, characterized by a reduced pain threshold.
• Metabolic changes beyond glucose, often seen in conditions like diabetes mellitus, can synergistically contribute to small fiber neuropathy.
• This suggests a broader role for various metabolic alterations in the development of small fiber neuropathy.

Purpose of the Study:

• To investigate the correlation between pain sensation and plasma metabolite changes in a healthy Japanese population.
• To identify specific metabolites associated with variations in pain thresholds.

Main Methods:

• Quantified pain sensation using the intraepidermal electrical stimulation index in 1021 healthy Japanese participants from the 2017 Iwaki Health Promotion Project.
• Categorized participants into low (n=751) and high (n=270) pain threshold groups based on the intraepidermal electrical stimulation index.
• Performed plasma metabolome analysis using capillary electrophoresis time-of-flight mass spectrometry.

Main Results:

• Metabolite set enrichment analysis identified a significant correlation between tryptophan metabolism and the intraepidermal electrical stimulation index across all participants (P < 0.05).
• Participants with a high pain threshold exhibited significantly decreased normalized levels of tryptophan.
• Linear regression analysis confirmed that the correlation between tryptophan concentration and the pain threshold remained significant after adjusting for multiple factors (β = -0.07615, P < 0.05).

Conclusions:

• Specific metabolic changes are implicated in the decline of pain thresholds.
• Abnormal tryptophan metabolism is significantly associated with an elevated pain threshold in the Japanese population.
• This association provides valuable insights into the pathology and potential clinical applications for small fiber neuropathy.