Neuropathic Pain Comorbid Cognitive Impairment and Vitamin D: A Narrative Review From Mechanisms to Clinical Management.

Neuropathic pain (NP) is not merely simple persistent pain but a complex pathological condition mediated by dysregulation across multiple systems, including the neuro-immune-endocrine axis. As a high-intensity endogenous stressor, persistent pain signals can deplete cognitive resources and trigger neuroinflammation and central sensitization, leading to cognitive impairment (CI) characterized by attention deficits and impaired working memory. Currently, mainstream pharmacological treatments for NP carry risks of addiction and may exacerbate CI. Therefore, there is an urgent need to develop synergistic intervention strategies that address both pain management and cognitive protection. Given that NP and CI share multiple pathological pathways, identifying interventions capable of simultaneously targeting multiple mechanisms has become a research hotspot. Vitamin D, a secosteroid hormone with both neuroprotective and immunoregulatory functions, is closely associated with an increased risk of NP and CI when deficient. Existing evidence suggests that Vitamin D may regulate the shared pathological mechanisms of these two diseases through multiple pathways, thus serving as a potential adjunctive strategy worthy of further investigation to alleviate the intertwined vicious cycle between NP and CI. This paper systematically reviews the shared pathological mechanisms between NP and CI, summarizes the latest research progress, and explores the multi-target mechanisms of Vitamin D in intervening in NP-CI comorbidity, aiming to promote the application of this safe and cost-effective nutritional strategy in dietary supplementations for NP-CI comorbidity.