Abstract

Diabetic neuropathy-induced allodynia is a distressing sensory abnormality characterized by the perception of pain in response to non-painful stimuli. This phenomenon significantly impairs the quality of life for individuals with diabetes. Primary afferent nerves, responsible for pain signal transmission, undergo structural and functional changes in diabetic neuropathy. Chronic hyperglycemia leads to nerve damage and sensitization of primary afferent nerves, contributing to aberrant pain processing. Mechanisms underlying allodynia include axonal degeneration, demyelination, metabolic disturbances, inflammation, and altered expression of ion channels and receptors. Upregulated sodium channels, such as Nav1.7 and Nav1.8, enhance nerve excitability, while changes in TRP channels (TRPV1, TRPA1) increase sensitivity to thermal and chemical stimuli. Altered opioid receptors, neurotransmitters (substance P, CGRP), and neurotrophic factors further modulate pain perception. Understanding primary afferent nerve function in diabetic neuropathy-induced allodynia may aid in developing targeted therapies, including channel blockers, TRP channel antagonists, and anti-inflammatory agents, to alleviate this debilitating symptom.