43: Lipid-lowering Drugs and Neuropathic Pain

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic neuropathic pain, , , , , , , , , , Pharmacological interventions

Background and Aims: Neuropathic pain (NP), characterized by somatosensory nervous system dysfunction, manifests as diabetic peripheral neuropathy (DPN), postherpetic neuralgia (PHN), and trigeminal neuralgia (TN). Emerging evidence suggests a potential link between dyslipidemia and NP pathogenesis. However, the neurological effects of statins, PCSK9 inhibitors, and NPC1L1 inhibitors remain controversial. This study investigates the causal relationships between these lipid-lowering agents and NP subtypes, providing evidence for personalized therapeutic strategies.

Methods: The study comprises two components, Cross-sectional analysis using the National Health and Nutrition Examination Survey (NHANES 1999–2004): Diabetic adults were evaluated for statin use and neuropathic symptoms. Weighted multivariable logistic regression models assessed statin-DPN associations, adjusting for demographics, lifestyle factors, and clinical parameters. Two-sample Mendelian randomization (MR) analysis: Genetic proxies for HMGCR, PCSK9, and NPC1L1 inhibition were derived from expression quantitative trait loci (eQTLs) and low-density lipoprotein cholesterol (LDL-C)-related GWAS data. Causality between lipid-lowering drug effects and NP subtypes (DPN, PHN, TN) was evaluated using inverse-variance weighted methods. Sensitivity analyses (MR-Egger, weighted median) and colocalization testing validated result robustness.

Results: MR analysis showed that HMGCR inhibitors (statins) were associated with an increased risk of DPN (OR = 4.20, 95% CI [2.42, 7.30]) and TN (OR = 1.52, 95% CI [1.14, 2.04]). PCSK9 inhibitors were linked to increased DPN risk (OR = 4.85, 95% CI [2.64, 8.91]), while NPC1L1 inhibitors were associated with increased TN risk (OR = 3.05, 95% CI [1.58, 5.91]). The NHANES analysis confirmed that statin use was significantly associated with an increased risk of DPN (OR = 1.46, 95% CI [1.05, 2.03]).

Conclusions: Statins and PCSK9 inhibitors are associated with increased DPN risk, while NPC1L1 inhibitors are linked to TN. Personalized treatment strategies may be needed to balance cardiovascular benefits and NP risk.

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Presenting Author: Ruilin He
Submitting Author: RUILIN HE

Senior Author: Zongbin Jiang

IASP 2026 Global Year theme of Neuropathic Pain: Yes