Causal Relationships Between Neuropathic Pain and Alzheimer's Disease: A Multi-Omics Mendelian Randomization Study with Exploratory Evidence of a Potential Protective Role of Diabetic Neuropathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41383962", "kind": "science-record", "revision": 2, "content_hash": "sha256:afda2c0bed0b82d62ffe43a42cc0d014472c8a3ae6e31704f838c4fcf9542f3d", "created_at": "2026-11-01T20:31:23Z", "updated_at": "2026-11-01T21:36:11Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Causal Relationships Between Neuropathic Pain and Alzheimer's Disease: A Multi-Omics Mendelian Randomization Study with Exploratory Evidence of a Potential Protective Role of Diabetic Neuropathy.", "doi": "10.2147/JPR.S554433", "pmid": "41383962", "authors": ["Xiao Li", "Chi Zhang", "Di Liu", "Hui Shang", "Kejia Wang", "Xianjian Lin", "Junyi Zheng"], "journal": "Journal of pain research", "year": 2025, "abstract": "Background: Neuropathic pain (NP) frequently co-occurs with Alzheimer's disease (AD), yet the causal relationship and underlying molecular mechanisms between the two remain unclear, necessitating further investigation to elucidate their intrinsic connection.\nMethods: This study employed a bidirectional two-sample Mendelian randomisation (MR) approach to systematically analyse the association between six NP subtypes and AD. Concurrently, functional annotation and transcriptomic analysis were conducted using the GTEx v10 and GEO GSE156184 databases to explore potential molecular mechanisms.\nResults: The study revealed a significant inverse causal effect of diabetic neuropathy (DN) on AD risk (OR=0.86, 95% CI: 0.77~0.95, P IVW=0.0043), with sensitivity analyses confirming the robustness of this finding. Further analysis indicated that DN-associated SNPs regulate four tissue-specific genes including FAM200A and GPC2. These genes exhibit differential expression in the DN transcriptome and are significantly enriched in key pathways such as mitochondrial function and autophagy.\nConclusion: This study provides the first evidence that DN may exert a protective effect against AD by regulating the aforementioned tissue-specific genes and associated pathways. This finding challenges the conventional understanding that chronic pain exacerbates AD and offers novel potential targets for developing therapeutic strategies. However, due to population limitations in the study, further experimental validation remains necessary.", "claims": [{"id": "claim-method", "statement": "Among these, the IVW method was selected as the primary analysis strategy", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41383962", "locator": "sections[3] \"MR Analysis\" paragraph 4", "quote": "Among these, the IVW method was selected as the primary analysis strategy"}], "state": "complete"}, {"id": "claim-data-access", "statement": "All original data and findings described in this study are available within the article, and any additional questions can be addressed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41383962", "locator": "sections[21] \"Data Sharing Statement\" paragraph 2", "quote": "All original data and findings described in this study are available within the article, and any additional questions can be addressed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study revealed a significant inverse causal effect of diabetic neuropathy (DN) on Alzheimer's disease (AD) risk.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "The study revealed a significant inverse causal effect of diabetic neuropathy (DN) on AD risk (OR=0.86, 95% CI: 0.77~0.95, PIVW=0.0043), with sensitivity analyses confirming the robustness of this finding."}, "evidence": [{"asset": "source:pmid:41383962", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The study revealed a significant inverse causal effect of diabetic neuropathy (DN) on AD risk (OR=0.86, 95% CI: 0.77~0.95, PIVW=0.0043), with sensitivity analyses confirming the robustness of this finding."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study revealed a significant inverse causal effect of diabetic neuropathy (DN) on Alzheimer's disease (AD) risk.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:41383962"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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